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253 Study Matches
Trial of Curcumin to Prevent Progression of Low-risk Prostate Cancer Under Active Surveillance
This is a prospective study to determine if the use of curcumin randomized against placebo will reduce cancer progression in patients with prostate cancer undergoing active surveillance.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yair Lotan
MALE
40 Years to 89 Years old
PHASE3
NCT03769766
STU 012018-071
Inclusion Criteria:
* Age between 40-89 years
* Biopsy proven, low-risk, localized prostate cancer (minimum of 8 cores)
* May have had biopsy within last 12 months
* ≤4 separate locations in the prostate involved with cancer. If multiple cores are obtained from same lesion or area than this will count as one location.
* Gleason score ≤6 with no Gleason pattern 4
* Clinical stage T1c-T2a/b
* Serum PSA ≤15 ng/ml
* Life expectancy \> 5 years
Exclusion Criteria:
* Any previous prostate cancer treatment (radiotherapy, chemotherapy, hormonal therapy, oral glucocorticoids, GnRH analogues, prostatectomy)
* Concurrent or previous use within 6 months of screening of any 5α-reductase inhibitor
* Use of anabolic steroids or drugs with antiandrogenic properties
* Prostate volume \>150 cm³
* Patients who are taking antiplatelet, anticoagulant agents or have a history of a bleeding disorder. Patients taking 81 mg of Aspirin will be allowed to enroll with close observation
* History of gastric or duodenal ulcers or untreated hyperacidity syndromes. Patients on stable doses (2 months of therapy) of GERD medication allowed.
* Patients who are currently taking Curcumin and are unwilling to stop or plan to take Curcumin during the study
* Patients with a history of gallbladder problems or gallstones or biliary obstruction, unless patient had cholecystectomy DRUG: Curcumin, DRUG: Placebo
Prostate Cancer, Prostate
prostate cancer, active surveillance, curcumin
UT Southwestern; Parkland Health & Hospital System
Standard Systemic Therapy With or Without Definitive Treatment in Treating Participants With Metastatic Prostate Cancer
This phase III trial studies how well standard systemic therapy with or without definitive treatment (prostate removal surgery or radiation therapy) works in treating participants with prostate cancer that has spread to other places in the body. Addition of prostate removal surgery or radiation therapy to standard systemic therapy for prostate cancer may lower the chance of the cancer growing or spreading.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
MALE
18 Years and over
PHASE3
NCT03678025
STU-2020-0492
Inclusion Criteria:
* STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: All patients must have a histologically or cytologically proven diagnosis of adenocarcinoma of the prostate. Patients with pure small cell carcinoma\* (SCC), sarcomatoid, or squamous cell carcinoma are not eligible. (\*morphology must be consistent with SCC; synaptophysin or chromogranin positive by immunohistochemical staining is insufficient to diagnose SCC).
* STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: Patients must have an intact prostate. No prior local therapy for prostate adenocarcinoma is allowed (e.g., brachytherapy, high-intensity focused ultrasound \[HIFU\], cryotherapy, laser ablative therapies). Any prior therapy for benign conditions, such as obstruction, are acceptable (e.g., transurethral resection of the prostate, greenlight laser ablation, microwave ablation).
* STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: Patients must have evidence of metastatic disease on technetium bone scan and computed tomography (CT) or magnetic resonance imaging (MRI) within 42 days prior to starting standard systemic therapy. Metastatic disease that is detected by positron emission tomography (PET) scan only (sodium fluoride \[NaF\], prostate-specific membrane antigen \[PSMA\], anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid \[FACBC\], carbon \[C\]11) but not conventional imaging (technetium \[Tc\]99 bone scan, CT or MRI) or solitary metastases by conventional imaging, must be confirmed histologically or cytologically.
* STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: Patients with known brain metastases are not eligible. Brain imaging studies are not required for eligibility if the patient has no neurologic signs or symptoms suggestive of brain metastasis. If brain imaging studies are performed, they must be negative for disease.
* STEP 1 REGISTRATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must have received no more than 28 weeks of standard systemic therapy (SST). SST is defined as current National Comprehensive Cancer Network (NCCN) guidelines for metastatic prostate cancer.
* STEP 1 REGISTRATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must not have progressed while on SST.
* STEP 1 REGISTRATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients with oligometastatic prostate cancer may receive metastasis directed therapy to up to four sites of disease prior to randomization.
* STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: Patients must have a complete physical examination and medical history within 28 days prior to registration.
* STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: Patients must have a PSA documented prior to initiation of SST and within 28 days prior to registration. Any additional PSAs measured while receiving SST should be recorded.
* STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: Patients must have a testosterone lab documented within 28 days prior to randomization. Any additional testosterone labs measured while receiving SST should be recorded as well as pretreatment initiation if available.
* STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated stage 0, I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years.
* STEP 1 REGISTRATION: SPECIMEN SUBMISSION CRITERIA: Patients must be offered the opportunity to participate in translational medicine studies and specimen banking for future studies.
* STEP 1 REGISTRATION: QUALITY OF LIFE CRITERIA: Patients who can complete Patient-Reported Outcome instruments in English, Spanish or French, must participate in the quality of life studies.
* STEP 1 REGISTRATION: REGULATORY CRITERIA: Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
* STEP 2 RANDOMIZATION: DISEASE-RELATED CRITERIA: As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.
* STEP 2 RANDOMIZATION: DISEASE-RELATED CRITERIA: Patients must have no evidence of disease progression during the 28 weeks of SST by PSA measure, bone scan and CT or MRI or symptomatic deterioration (as defined by physician discretion) within 28 days prior to randomization.
* STEP 2 RANDOMIZATION: DISEASE-RELATED CRITERIA: Patients must have consultation with a urologist and have surgically resectable disease regardless of definitive treatment intent or randomization.
* STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must have received between 22 and 28 weeks of SST as measured from the date of first hormonal therapy or surgical castration. SST is defined by current NCCN guidelines for metastatic prostate cancer.
* STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must not be planning to receive docetaxel after randomization.
* STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Any toxicities from SST must have resolved to =\< grade 1 (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0) prior to randomization.
* STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients may have received elective metastasis directed therapy to oligometastatic sites (=\< 4 sites). All treatment must be completed prior to randomization.
* STEP 2 RANDOMIZATION: CLINICAL/LABORATORY CRITERIA: Patients must have a PSA performed within 28 days prior to randomization.
* STEP 2 RANDOMIZATION: CLINICAL/LABORATORY CRITERIA: Patients must have a testosterone \< 50 ng/dL within 28 days prior to randomization.
* STEP 2 RANDOMIZATION: CLINICAL/LABORATORY CRITERIA: Patients must have a Zubrod performance status of 0 ? 1 within 28 days prior to randomization. DRUG: Abiraterone, DRUG: Bicalutamide, DRUG: Degarelix, DRUG: Docetaxel, DRUG: Flutamide, DRUG: Goserelin Acetate, DRUG: Histrelin Acetate, DRUG: Leuprolide Acetate, DRUG: Nilutamide, PROCEDURE: Orchiectomy, DRUG: Prednisone, OTHER: Quality-of-Life Assessment, RADIATION: Radiation Therapy, PROCEDURE: Radical Prostatectomy, DRUG: Triptorelin
Castration Levels of Testosterone, Metastatic Prostatic Adenocarcinoma, Stage IV Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8, Prostate
UT Southwestern; Parkland Health & Hospital System
Gemcitabine and Cisplatin Without Cystectomy for Patients With Muscle Invasive Bladder Urothelial Cancer and Select Genetic Alterations
This phase II trial studies how well gemcitabine hydrochloride and cisplatin work in treating participants with invasive bladder urothelial cancer. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
ALL
18 Years and over
PHASE2
NCT03609216
STU-2020-0422
Inclusion Criteria:
* Step 1 Patient Registration Eligibility Criteria
* Histologically confirmed muscle-invasive urothelial carcinoma of the bladder. Urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed, provided the extent of disease is confirmed via imaging and/or examination under anesthesia (EUA). The diagnostic TURBT sample must have been obtained within 60 days prior to registration
* 20 unstained slides (10 micron thickness) of formalin-fixed paraffin-embedded (FFPE) pre-treatment diagnostic transurethral resection (TUR) specimen available (for sequencing), with 2 (5 micron) slides at the start and end of the 20 slides, for a total of 22 unstained slides. An FFPE block is also acceptable
* Clinical stage T2-T4aN0/xM0 disease
* Medically appropriate candidate for radical cystectomy as assessed by surgeon
* No concomitant multifocal carcinoma in situ; a single focus is allowed
* A single muscle-invasive bladder tumor measuring ≤5 cm in size as defined by the surgeons at cystoscopic evaluation. When documented, pathologic size at cystoscopy and TURBT will take precedence over radiographic measurements of tumor size.
* No clinical or radiographic evidence for locally advanced or metastatic disease
* No prior anti-PD-1 or anti PD-L1 therapies, or systemic chemotherapy within the past 5 years (prior intravesical induction immunotherapy for non-muscle invasive disease is allowed, defined as BCG x6 doses and maintenance therapy); BCG refractory disease, defined as disease recurrence within 3 months of BCG therapy, is not allowed. Intravesical chemotherapy is allowed.
* No prior radiation therapy to the bladder or prostate
* No major surgery or radiation therapy =\< 4 weeks of registration (TURBT is allowed).
* Not pregnant and not nursing. This study involves an agent that has known genotoxic, mutagenic and teratogenic effects. For women of childbearing potential only, a negative pregnancy test done =\< 14 days prior to registration is required
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Absolute neutrophil count (ANC) \>= 1,000/mm\^3
* Platelet count \>= 100,000/mm\^3
* Calculated creatinine clearance ≥ 55 mL/min using formula per institutional standard or investigator's discretion. The same formula should be used to calculate all subsequent creatinine clearances.
* Total bilirubin =\< 1.5 x upper limit of normal (ULN)
\* (For patients with documented Gilbert's syndrome Total Bilirubin =\< 3 x ULN)
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x ULN
* Alkaline phosphatase =\< 2.5 x ULN
* No evidence of New York Heart Association (NYHA) functional class III or IV heart disease
* No ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade \>= 2
* No pre-existing sensory grade \>= 2 neuropathy
* No pre-existing grade \>= 2 hearing loss
* No serious intercurrent medical or psychiatric illness, including serious active infection
* None of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
* No known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the drugs used in this trial. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy, when indicated
* No history of allergic reaction attributed to compounds of similar chemical or biologic composition to the agents used in this study
* No concurrent treatment on another clinical trial; supportive care trials or non-therapeutic trials (e.g., quality of life) are allowed
* No prior malignancy except for: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years. Patients with localized prostate cancer who are being followed by an active surveillance program are also eligible
* Step 2 Patient Registration Eligibility Criteria
* Patients must have completed 4 or more cycles of protocol-directed chemotherapy and DDR gene results must be available
* Step 3 Patient Registration Eligibility Criteria (only patients with a DDR gene alteration)
* Deleterious alteration within 1 or more of 9 pre-defined DDR genes within the pre-treatment TURBT deoxyribonucleic acid (DNA)
* Cystoscopy and imaging performed to determine stage/treatment assignment DRUG: Gemcitabine Hydrochloride, DRUG: Cisplatin, BIOLOGICAL: Pegfilgrastim, PROCEDURE: Conventional Surgery, PROCEDURE: Radical Cystectomy, OTHER: Chemoradiotherapy
Infiltrating Bladder Urothelial Carcinoma, Stage II Bladder Urothelial Carcinoma, Stage III Bladder Urothelial Carcinoma
UT Southwestern
Peri-Operative Immune Checkpoint Inhibition and Cryoablation in Women With Triple-negative Breast Cancer
The purpose of this study is to determine the impact of pre-operative cryoablation, and immune checkpoint inhibition (ICI) on on 3-year Event Free Survival (EFS), in women with residual hormone receptor negative, HER2-negative ("triple negative") resectable breast cancer after taxane-based neoadjuvant chemotherapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Heather McArthur
FEMALE
18 Years and over
PHASE2
NCT03546686
STU-2021-1043
Inclusion Criteria:
• Women age 18 years or older
• Confirmed histologic diagnosis of invasive carcinoma of the breast
• Pathology confirmation of invasive carcinoma (reported or requested and pending)
• ER, PR and HER2 negative on outside or Cedars Sinai biopsy report, where ER and PR negative are defined as staining present in ≤10% of invasive cancer cells by IHC, and HER2-negative is defined as IHC 0-1+ or FISH \<2.0. If ER, PR and HER2 status are not reported the results must be requested and pending.
• Operable tumor measuring ≥1.0 cm in maximal diameter
• Any nodal status allowed, including negative nodal status.
• Multifocal and multicentric disease is permitted if all foci have been biopsied and also meet the criteria for TNBC.
• Synchronous bilateral invasive breast cancer is permitted if all foci have been biopsied and also meet the criteria for TNBC.
• No indication of distant metastases
• Total mastectomy or lumpectomy planned
• Tumor amenable to cryoablation as determined by a study radiologist
• ECOG performance status score of 0 or 1.
• Screening laboratory values must meet the following criteria: * White blood cells (WBCs) ≥ 2000/μL * Absolute neutrophil count (ANC) ≥ 1500/μL * Platelets ≥ 100 x 103/μL ii. Hemoglobin ≥ 9.0 g/dL iii. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below): Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL * AST/ALT ≤ 3 x upper limit of normal (ULN) * Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert's syndrome, who must have total bilirubin \< 3.0 mg/dL)
• Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab and, ipilimumab, and pembrolizumab to undergo five half-lives) after the last dose of investigational drug.
• Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG). Women must not be breastfeeding
• Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.
Exclusion Criteria:
* Medical history and concurrent diseases
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Note: Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
• Any underlying medical or psychiatric condition, which in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of AEs, such as a condition associated with frequent or poorly controlled diarrhea.
• A history of invasive malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer, or ovarian cancer.
• Has known active hepatitis B or hepatitis C. * Prohibited Treatments and/or Therapies
• Chronic use of immunosuppressants and/or systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses). Brief periods of steroid use, for example for the management of chemotherapy-associated toxicities, are allowed. The use of corticosteroids on study is allowed for the treatment of immune related adverse events (irAEs) and other medical conditions including adrenal insufficiency.
• Any non-oncology live vaccine therapy used for prevention of infectious diseases within 3 weeks prior to first dose of ICI.
• Prior investigational agents within 3 weeks prior to ICI administration
DRUG: Pembrolizumab, PROCEDURE: Core Biopsy/Cryoablation, PROCEDURE: Breast Surgery, DRUG: Ipilimumab, DRUG: Nivolumab
Breast Cancer, Breast - Female
Hormone Receptor Negative, Her2- Negative, Resectable Breast Cancer, breast cancer, immunotherapy, Ipilimumab, Nivolumab, Cryoablation
UT Southwestern; Parkland Health & Hospital System
Regional Radiotherapy in Biomarker Low-Risk Node Positive and T3N0 Breast Cancer (TAILOR RT)
The purpose of this study is to compare the effects on low risk breast cancer receiving usual care that includes regional radiation therapy, with receiving no regional radiation therapy. Researchers want to see if not giving this type of radiation treatment works as well at preventing breast cancer from coming back.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Ann Leitch
FEMALE
35 Years and over
PHASE3
NCT03488693
STU-2018-0236
Inclusion Criteria:
* Patients must be women with newly diagnosed histologically proven invasive carcinoma of the breast with no evidence of metastases, staged as per site standard of care.
* Patients must have been treated by BCS or mastectomy with clear margins of excision. Post-mastectomy positive margins for invasive disease and/or DCIS is not allowed. Multifocal disease (i.e. the presence of two or more foci or breast cancer within the same breast quadrant) and multicentric disease (i.e. the presence of two or more foci of breast cancer in different quadrants of the same breast) are allowed.
* Patients with T3N0 disease are eligible.
* Patients with disease limited to nodal micrometastases are eligible
* Patients with nodal macrometastases (\>2mm) treated by axillary dissection must have 1-3 positive axillary nodes (macrometastases, \> 2 mm).
* Patients treated by mastectomy and SLNB alone must have only 1-2 positive axillary nodes (macrometastases, \> 2 mm).
* Patients must be ER ≥ 1% and HER2 negative on local testing
* Patients must have an Oncotype DX recurrence score ≤25 obtained from testing of breast tumour tissue from a core biopsy or from the surgical specimen.
* Patient must consent to provision of, and investigator(s) must agree to submit to the CCTG Central Tumour Bank, a representative formalin fixed paraffin block of tumour tissue in order that the specific correlative marker assays described in the protocol may be conducted
* Patient must consent to provision of samples of blood in order that the specific correlative marker assays described in the protocol may be conducted.
* Patients must have had endocrine therapy initiated or planned for ≥ 5 years. Premenopausal women will receive ovarian ablation plus aromatase inhibitor therapy or tamoxifen if adjuvant chemotherapy was not administered. For all patients, endocrine therapy can be given concurrently or following RT.
* Patients may or may not have had adjuvant chemotherapy.
* RT must commence within 16 weeks of definitive surgery if the patient is not treated with chemotherapy. If adjuvant chemotherapy is given, RT must begin within 12 weeks after the last dose. (Note: adjuvant chemotherapy may be ongoing at the time of randomization). Definitive surgery is defined as the last breast cancer-related surgery.
* Patient's ECOG performance status must be 0, 1 or 2.
* Patient's age must be ≥ 35 years.
* For the first 736 eligible English or French-speaking subjects who have agreed to optional questionnaire completion: Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life, health utilities and lost productivity questionnaires in either English or French (note: enrollment completed 2022Aug02)
* Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements
* Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
* In accordance with CCTG policy, protocol treatment is to begin within 6 weeks of patient randomization.
* Women of childbearing potential must have agreed to use an effective contraceptive method. A woman is considered to be of "childbearing potential" if she has had menses at any time in the preceding 12 consecutive months.
Exclusion Criteria:
* Patients with nodal disease limited to isolated tumour cells (pN0i+ \< 0.2 mm).
* Patients with pT3N1 and pT4 disease (Note: patients with T3N0 are eligible).
* Any prior history, not including the index cancer, of ipsilateral invasive breast cancer or ipsilateral DCIS treated with radiation therapy. (Patients with synchronous or previous ipsilateral LCIS are eligible.)
* Synchronous or previous contralateral invasive breast cancer. (Patients with contralateral DCIS are eligible unless previously treated with radiation.)
* History of non-breast malignancies except adequately treated non-melanoma skin cancers, in situ cancers treated by local excision or other cancers curatively treated with no evidence of disease for ≥ 5 years.
* Patients who are pregnant.
* Patients that have had prior ipsilateral chestwall/thoracic radiation.
* Patients treated with chemo or endocrine therapy administered in the neoadjuvant setting for breast cancer. Endocrine therapy exposure 12 weeks or less prior to surgery is permitted.
* Patients with serious non-malignant disease (e.g. cardiovascular, scleroderma etc.) which would preclude RT.
* Patients with any serious active or co-morbid medical conditions, laboratory abnormality, psychiatric illness, active or uncontrolled infections, or serious illnesses or medical conditions that would prevent the patient from participating or to be managed according to the protocol (according to investigator's decision). RADIATION: Radiation, OTHER: No Radiation
Breast Cancer, Breast - Female
UT Southwestern; Parkland Health & Hospital System
Mevrometostat Treatment of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma
A Phase 1 Dose Escalation and Expanded Cohort Study Of PF-06821497 (Mevrometostat) in Adult Patients With Relapsed/Refractory Small Cell Lung Cancer (SCLC), Castration Resistant Prostate Cancer (CRPC) And Follicular Lymphoma (FL).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE1
NCT03460977
STU-2022-0733
Part 1 and Part 2 (Closed for enrollment).
Part 3 Key
Inclusion Criteria:
* Histological or cytological diagnosis of castration resistant prostate cancer.
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-2 with expected life expectancy of at least 6 months.
* Adequate bone marrow, renal, and liver function
Part 3 Key Exclusion Criteria:
* Prior irradiation to \>25% of the bone marrow.
* QTcF interval \>480 msec at screening.
* Hypertension that cannot be controlled by medications (\>150/90 mmHg despite optimal medical therapy).
* Known or suspected hypersensitivity to PF 06821497 or any components or enzalutamide (CRPC)
* Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery.
* Current use or anticipated need for food or drugs that are known strong and moderate CYP3A4/5 inducers or inhibitors
* Prior enzalutamide within the last 4 weeks
* DDI SUBSTUDY:
* history of CHF or evidence of ventricular dysfunction
* fructose intolerance
* coadministration of CYP3A4 substrates DRUG: Mervometostat (PF-06821497), DRUG: Enzalutamide
Metastatic Castration Resistant Prostate Cancer (mCRPC), Small Cell Lung Cancer (SCLC), Follicular Lymphoma (FL)
EZH2, enhancer of zeste homolog 2, castrate resistant prostate cancer, prostatecancer-study.com, mCRPC, efficacy, safety, pharmacokinetics, pharmacodynamics, dose escalation, dose expansion, open-label, small cell lung cancer, SCLC, follicular lymphoma, FL, relapsed, refractory
UT Southwestern
Chemotherapy Before Surgery and Radiation Therapy or Surgery and Radiation Therapy Alone in Treating Patients With Nasal and Paranasal Sinus Cancer That Can Be Removed by Surgery
This randomized phase II trial studies how well chemotherapy before surgery and radiation therapy works compared to surgery and radiation therapy alone in treating patients with nasal and paranasal sinus cancer that can be removed by surgery. Drugs used in chemotherapy, such as docetaxel, cisplatin, and carboplatin work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving chemotherapy before surgery and radiation therapy may make the tumor smaller and reduce the amount of normal tissue that needs to be removed and treated with radiation.
Call 1-888-980-6050
canceranswerline@utsouthwestern.edu
Saad Khan
ALL
18 Years and over
PHASE2
NCT03493425
STU 062018-056
Inclusion Criteria:
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* General physical condition compatible with the proposed chemotherapy and surgery
* Stage T3 or T4a, histologically-confirmed NPNSCC requiring orbital or skull base resection:
* Stages T3 and T4a disease will be included regardless of nodal status (N0 or N1-3), provided that surgical therapy would require orbital or skull base resection
* The surgical oncologist in each institution will determine the need for resection of the orbit OR base of skull at baseline for patients on both Arms A and B and following neo-adjuvant chemotherapy for patients on Arm B
* Resection of skull base will be deemed necessary according to skull base bone erosion by CT or marrow involvement by MRI is noted; for any disease abutting the skull base; or for ethmoid sinus or frontal sinus involvement
* Resection of orbital contents will be deemed necessary according to skull base society guidelines, based on involvement of periorbital fat documented by MRI imaging
* Patients must be deemed surgically resectable by the surgical teams at each institution and must have a determination of degree of anticipated structure preservation of orbit and skull base; this needs to be determined prior to randomization
* Patients may not be receiving investigational agents at time of registration, or at any time while on study and during the 4 weeks preceding enrollment
* Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxel and/or both platinum-based chemotherapy agents are excluded; patient must be able to receive at least one of the two proposed chemotherapy regimens
* Patients with evidence of distant metastases or leptomeningeal disease (LMD) are excluded
* Patients must not have received previous irradiation for head and neck tumor, skull base, or brain tumors
* Patients with uncontrolled inter-current illnesses which in the opinion of the investigator will interfere with the ability to undergo therapy including chemotherapy are excluded
* Patients with a history of a different malignancy are excluded, unless the disease has not progressed for \>= 2 years
* Absolute neutrophil count (ANC) \> 1500/mm\^3 =\< 2 weeks prior to randomization
* Hemoglobin (Hgb) \> 8.0 g/dL =\< 2 weeks prior to randomization
* Platelet count \> 100,000/mm\^3 =\< 2 weeks prior to randomization
* Creatinine clearance of \> 60 ml/min; creatinine clearance may be measured or calculated; if calculating, creatinine clearance, use the Cockroft-Gault formula =\< 2 weeks prior to randomization
* Total bilirubin within normal limits (must be obtained =\< 2 weeks prior to randomization)
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) must be within the range allowing for eligibility, must be obtained \< 2 weeks prior to randomization
* Alkaline phosphatase must be within the range allowing for eligibility, must be obtained \< 2 weeks prior to randomization
* Patients with a prior history of squamous cell or basal carcinoma of the skin or in situ cervical cancer must have been curatively treated
* No current peripheral neuropathy \> grade 2 at time of randomization
* Patients must not have any co-existing condition that would preclude full compliance with the study; no prior history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
* Women must not be pregnant or breast-feeding
* All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
* A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study
* Patients must have measurable disease; MRI and/or PET/CT scans need to be performed within 2 weeks prior to registration DRUG: Carboplatin, DRUG: Cisplatin, DRUG: Docetaxel, RADIATION: Image Guided Radiation Therapy, RADIATION: Intensity-Modulated Radiation Therapy, OTHER: Laboratory Biomarker Analysis, OTHER: Questionnaire Administration, PROCEDURE: Therapeutic Conventional Surgery
Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v6 and v7, Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7
Neurocognitive Decline in Patients With Brain Metastases
The phase I component of the study is to identify maximal tolerated dose (MTD). The phase II is to evaluate neurocognitive decline.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Zabihullah Wardak
ALL
18 Years and over
PHASE1
NCT03508752
STU 122016-064
Inclusion Criteria:
• Age ≥ 18 years.
• ECOG Performance Score of 2 or better/Karnofsky Performance score of 50-60 or better.
• Biopsy-proven non-hematopoietic malignancy, except for germ cell cancer. Small cell lung carcinoma is eligible for this study.
• Six or more metastases on diagnostic or treatment planning imaging, which include either CT Brain (with contrast) or MR Brain (with or without contrast) imaging.
• Largest tumor \<= 4 cm.
• No prior SRS to the lesions which will be treated on protocol.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
• Prior whole brain radiotherapy
• Patients with leptomeningeal metastasis. (NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion.)
• Patients with life expectancy \< 4 months.
• Psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
RADIATION: Stereotactic Radiosurgery
Brain Metastases, Brain and Nervous System
UT Southwestern; Parkland Health & Hospital System
Adoptive Cell Therapy Long-term Follow-up (LTFU) Study
This trial will evaluate long term safety of participants who have received AdaptImmune (ADP) adoptive cell therapy for up to 15 years following last adoptive cell therapy infusion.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Samuel John
ALL
4 Years and over
PHASE1
NCT03391778
STU-2019-1522
Inclusion Criteria:
* Participants who have received at least one dose of ADP adoptive cell therapy agent.
* Participants who have completed ADP sponsored or supported interventional study or have withdrawn from it.
* Participants who have completed treatment as part of managed access to a GSK adoptive cell therapy.
* Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* The investigator is responsible for review of medical history.
* Capable of giving signed informed consent.
Exclusion Criteria:
• None
BIOLOGICAL: ADP adoptive cell therapy
Neoplasms, Soft Tissue
Long Term Follow Up, Adoptive Cell Therapy, Replication Competent Lentivirus
Children’s Health
S1501 Dual Observational and Randomized Cohort Study of Patients With Metastatic HER-2+ Breast Cancer at Risk of Cardiac Toxicity
This trial has two cohorts of patients with human epidermal growth factor receptor (HER)-2-positive breast cancer that has spread to other places in the body. All patients must be receiving trastuzumab-based treatment. Both cohorts are being observed for cardiac toxicity. The largest cohort (currently open to accrual) is observational, and contains patients who are taking a beta blocker, ACE inhibitor, or ARB as well as their trastuzumab-based treatment. The goal is to understand how common cardiac problems are in this group of patients at high risk. The smaller cohort (currently closed to accrual) is randomized. Patients in this second cohort are randomized to either carvedilol or no treatment, with the goal of seeing whether carvedilol (used to treat heart failure and high blood pressure) may prevent the heart from side effects of chemotherapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Vlad Zaha
ALL
18 Years and over
PHASE3
NCT03418961
STU-2021-1112
Inclusion Criteria:
* STEP 1 REGISTRATION
Patients must:
• Have metastatic breast cancer, AND
• Be initiating within 11 calendar days of Step 1 Registration OR be continuing trastuzumab-based HER-2 targeted therapy without concurrent anthracyclines, AND
• Be receiving the trastuzumab-based HER-2 targeted therapy for metastatic disease in first, second, third-, or fourth-line setting. Patients may have brain metastasis. There is no limit for number of doses of HER-2 targeted therapy prior to registration. Examples of eligible HER-2 targeted therapy: * Trastuzumab or a trastuzumab biosimilar * Trastuzumab + chemotherapy or hormonal therapy * Trastuzumab + other HER-2 targeted agent with or without chemotherapy (such as pertuzumab, lapatinib, and tucatinib) * Ado-trastuzumab (Kadcyla®) * Fam-trastuzumab deruxtecan (Enhertu) NOTE: Patients on lapatinib without trastuzumab are not eligible. Planned treatment with concurrent HER-2 targeted therapy and anthracyclines is not permitted. * Patients must be at increased risk for cardiotoxicity defined by at least one of the following:
• Previous anthracycline exposure OR
• 1 or more of the following risk factors for heart disease: * LVEF 50-54% by local ECHO read\* * Age ≥ 65 * BMI ≥ 30 kg/m2 * Current or prior anti-hypertensive therapy * Diagnosis of coronary artery disease (CAD) * Diagnosis of diabetes mellitus * Diagnosis of atrial fibrillation/flutter Note: ECHO can be performed at any time prior to registration with the most recent being sent. * Patients must not have taken within 21 days prior to Step 1 Registration, be currently taking at the time of Step 1 Registration or planning to take once registered to Step 1 a beta blocker, ARB, or ACE inhibitor, in order to be randomized (Arms 1 and 2). Patients enrolling in the observational cohort (Arm 3) must be currently taking a beta blocker, ARB, or ACE inhibitor at the time of Step 1 Registration. * Patients must have a Zubrod Performance status of 0-2 * Patients must have a complete physical examination and medical history within 28 days prior to registration * Patients must have LVEF \>= 50% echocardiogram (2D or 3D) within 28 days prior to registration. The echocardiogram must be obtained from a S1501 validated ECHO laboratory (lab) and submitted for central review by the S1501 ECHO core lab. If a 3D echocardiogram is performed at baseline, sites must ensure that standard 2D images, including 40chamber and 2-chamber views, are also obtained and submitted at subsequent timepoints. All follow-up echocardiograms (every 12 weeks) must be performed using 2D imaging to allow for standardized assessments. Follow-up scans must be completed at a site that can provide 2D images per protocol requirements. The echocardiograms cannot be submitted for central read until after Step 1 registration is complete. * Patients must have adequate hepatic function as evidenced by all of the following within 28 days prior to registration: * Serum bilirubin \< 3.0 x institutional upper limit of normal (IULN) * Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) and serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) \< 5.0 x IULN * Patients must not be dialysis dependent * No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, prostate cancer on active surveillance, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years * Patients must not be pregnant or nursing due to potential fetal or nursing infant harm; women/men of reproductive potential must have agreed to use an effective contraceptive method, a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures * Patients must be willing to submit blood specimens * Sites must seek additional patient consent for the future use of specimens * Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines * For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and CIRB regulations. * As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system * STEP 2 REGISTRATION (Randomization) * Patients must not be registered to step 2 until confirming via RAVE EDC that the patient's LVEF by echocardiogram was \>= 50% by central review. Patients must be registered within 21 calendar days of submission of the ECHO study/ * Site must verify that there is no known change in the step 1 eligibility since initial registration
DRUG: Carvedilol, OTHER: Laboratory Biomarker Analysis, OTHER: Patient Observation
Cardiotoxicity, HER2/Neu Positive, Metastatic Malignant Neoplasm in the Brain, Recurrent Breast Carcinoma, Stage IV Breast Cancer AJCC v6 and v7, Breast - Female
UT Southwestern
Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy (ALLELE)
The purpose of this study is to determine the clinical benefit and characterize the safety profile of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of (1) solid organ transplant (SOT) after failure of rituximab (SOT-R) and rituximab plus chemotherapy (SOT-R+C) or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
ALL
Not specified
PHASE3
NCT03394365
STU-2018-0349
Inclusion Criteria:
• Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these (C-SOT); or prior allogeneic HCT (C-HCT).
• A diagnosis of locally assessed, biopsy-proven EBV+ PTLD.
• Availability of appropriate partially HLA-matched and restricted tabelecleucel has been confirmed by the sponsor.
• Measurable, 18F-deoxyglucose (FDG)-avid (Deauville score ≥ 3) systemic disease using Lugano Classification response criteria by positron emission tomography (PET)-diagnostic computed tomography (CT), except when contraindicated or mandated by local practice, then magnetic resonance imaging (MRI) may be used. For participants with treated central nervous system (CNS) disease, a head CT and/or brain/spinal MRI as clinically appropriate will be required to follow CNS disease response per Lugano Classification response criteria.
• Treatment failure of rituximab or interchangeable commercially available biosimilar monotherapy (C-SOT-R or C-HCT) or rituximab plus any concurrent or sequentially administered chemotherapy regimen (C-SOT-R+C) for treatment of PTLD.
• Males and females of any age.
• Eastern Cooperative Oncology Group performance status ≤ 3 for participants aged ≥ 16 years; Lansky score ≥ 20 for participants \< 16 years.
• For C-HCT only: If allogeneic HCT was performed as treatment for an acute lymphoid or myeloid malignancy, the underlying primary disease for which the participant underwent transplant must be in morphologic remission.
• Adequate organ function.
• Absolute neutrophil count ≥ 1000/μL, (C-SOT) or ≥ 500/μL (C-HCT), with or without cytokine support.
• Platelet count ≥ 50,000/μL, with or without transfusion or cytokine support. For C-HCT, platelet count \< 50,000/μL but ≥ 20,000/μL, with or without transfusion support, is permissible if the participant has not had grade ≥ 2 bleeding in the prior 4 weeks (where grading of the bleeding is determined per the National Cancer Institute's Common Terminology Criteria for Adverse Events \[CTCAE\], version 5.0).
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin each \< 5 × the upper limit of normal; however, ALT, AST, and total bilirubin each ≤ 10 × upper limit of normal is acceptable if the elevation is considered by the investigator to be due to EBV and/or PTLD involvement of the liver as long as there is no known evidence of significant liver dysfunction.
• Participant or participant's representative is willing and able to provide written informed consent.
Exclusion Criteria:
• Currently active Burkitt, T-cell, NK/T-cell lymphoma/LPD, Hodgkin, plasmablastic, transformed lymphoma, active hemophagocytic lymphohistiocytosis, or other malignancies requiring systemic therapy.
• Daily steroids of \> 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing methotrexate, or extracorporeal photopheresis.
• Untreated CNS PTLD or CNS PTLD for which the participant is actively receiving CNS-directed chemotherapy (systemic or intrathecal) or radiotherapy at enrollment. NOTE: Participants with previously treated CNS PTLD may enroll if CNS-directed therapy is complete.
• Suspected or confirmed grade ≥ 2 graft-versus-host disease (GvHD) per the Center for International Blood and Marrow Transplant Research consensus grading system at enrollment.
• Ongoing or recent use of a checkpoint inhibitor agent (eg, ipilimumab, pembrolizumab, nivolumab) within 3 drug half-lives from the most recent dose to enrollment.
• For C-HCT: active adenovirus viremia.
• Need for vasopressor or ventilatory support.
• Antithymocyte globulin or similar anti-T cell antibody therapy ≤ 4 weeks prior to enrollment.
• Treatment with Epstein-Barr virus cytotoxic T lymphocytes or chimeric antigen receptor T cells directed against B cells within 8 weeks of enrollment (C-SOT or C-HCT), or unselected donor lymphocyte infusion within 8 weeks of enrollment (C-HCT only).
• Female who is breastfeeding or pregnant or female of childbearing potential or male with a female partner of childbearing potential unwilling to use a highly effective method of contraception.
• Inability to comply with study-related procedures.
• Any medical condition or organ system dysfunction that in the investigator';s opinion, could compromise the participant's safety or ability to complete the study.
BIOLOGICAL: tabelecleucel
Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Solid Organ Transplant Complications, Lymphoproliferative Disorders, Allogeneic Hematopoietic Cell Transplant, Stem Cell Transplant Complications, Other
Epstein-Barr Virus (EBV)-associated Lymphoproliferative Disease (LPD), Epstein-Barr Virus (EBV), Cytotoxic T lymphocyte (CTL), Cancer After Transplant, Kidney transplant, Renal transplant, Liver transplant, Heart transplant, Lung transplant, Intestinal transplant, Pancreas transplant, Post-transplant Lymphoma, Solid Organ Transplant (SOT), Bone Marrow Transplant Complications, Epstein-Barr Virus-specific Cytotoxic T Lymphocytes (EBV-CTL), Hematopoietic Cell Transplant (HCT), Hematopoietic Stem Cell Transplantation (HSCT), Allogeneic Hematopoietic Cell Transplant, Allogeneic, Off-The-Shelf T-cell Immunotherapy
Children’s Health
Study Evaluating Safety and Efficacy of JCAR017 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
This is a Phase 1/2, open-label, multicenter study to determine the efficacy and safety of JCAR017 in adult subjects with relapsed or refractory CLL or SLL. The study will include a Phase 1 part to determine the recommended dose of JCAR017 monotherapy in subjects with relapsed or refractory CLL or SLL, followed by a Phase 2 part to further assess the efficacy and safety of JCAR017 monotherapy treatment at the recommended dose. A separate Phase 1 cohort will assess the combination of JCAR017 and concurrent ibrutinib. Another separate Phase 1 cohort will assess the combination of JCAR017 and concurrent venetoclax. In all subjects, the safety, efficacy, and pharmacokinetics (PK) of JCAR017 will be evaluated.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Farrukh Awan
ALL
18 Years and over
PHASE1
NCT03331198
STU-2019-0562
Inclusion Criteria:
* Diagnosis of:
• CLL with an indication for treatment based on the Investigator's opinion and measurable disease, or
• SLL (lymphadenopathy and/or splenomegaly and \< 5×10\^9 CD19+ CD5+ clonal B lymphocytes/L \[\< 5000/µL\] in the peripheral blood at diagnosis with measurable disease that is biopsy-proven SLL) * Subjects (other than those in the ibrutinib + JCAR017 combination therapy and DEME cohort) must have received and failed Bruton tyrosine kinase inhibitor (BTKi) treatment or have been deemed ineligible for BTKi therapy. * Subjects in the JCAR017 monotherapy cohorts must have received previous treatment as follows:
• Monotherapy cohorts EXCEPT DEME cohort: Subjects with CLL or SLL and high-risk features must have failed at least 2 lines of prior therapy.
• Monotherapy cohorts EXCEPT DEME cohort: Subjects with CLL or SLL and standard-risk features must have failed at least 3 lines of prior therapy.
• DEME cohort ONLY: Subjects with relapsed or refractory CLL or SLL, irrespective of cytogenetic risk features, must have received at least 2 lines of prior therapy including a BTKi and a BCL2i. * Subjects in the ibrutinib + JCAR017 combination therapy cohort must either:
• be receiving ibrutinib and progressing at the time of study enrollment
• be receiving ibrutinib for at least 6 months with a response less than complete response/remission (CR) and have high-risk features as defined in inclusion criterion 5a
• have BTK or PLCgamma2 mutations per local laboratory assessment, with or without progression on ibrutinib
• have previously received ibrutinib and have no contraindications to restarting ibrutinib * Eastern Cooperative Oncology Group performance status of ≤ 1 * Assessed by the Investigator to have adequate bone marrow function to receive lymphodepleting chemotherapy * Adequate organ function, defined as:
• Serum creatinine ≤ 1.5 × age-adjusted upper limit of normal (ULN) OR calculated creatinine clearance \> 30 mL/min
• Alanine aminotransferase ≤ 5 × ULN and total bilirubin \< 2.0 mg/dL (or \< 3.0 mg/dL for subjects with Gilbert's syndrome or leukemic infiltration of the liver)
• Adequate pulmonary function, defined as ≤ Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 dyspnea and saturated oxygen (SaO2) ≥ 92% on room air
• Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40% as assessed by echocardiogram or multiple uptake gated acquisition scan performed within 30 days prior to determination of eligibility * Subject either currently has central vascular access or is a candidate to receive central vascular access or peripheral vascular access for leukapheresis procedure. * If prior CD19-targeted therapy has been administered, subject must have CD19-positive disease confirmed by immunohistochemistry or flow cytometry since completing the prior CD19-targeted therapy. * Subjects in ibrutinib + JCAR017 combination cohort must have progressed on a BTKi and have received prior therapy with venetoclax * Subjects in venetoclax + JCAR017 combination cohort must:
• have failed at least 1 prior line of therapy, including failed BTKi therapy or have been deemed ineligible to receive BTKi
• be venetoclax naive (required for dose expansion) or
• if prior venetoclax (only for dose escalation)
• have no contraindictions to re-initiation of venetoclax based on prior intolerance and have had at least 6 months elapsed since the last dose of venetoclax, if either, best response was stable disease, or subject experienced disease progression on venetoclax, or within 6 months of venetoclax discontinuation * subjects in the venetoclax + JCAR017 combination must have hemoglobin \>=9 g/dL, absolute neutrophil count \>=500mm3 and platelets\>= 75,000/mm3, unless cytopenias are judged by investigator to be due to CLL infiltration of the bone marrow * must have diagnosis of CLL or SLL with an indication for treatment based on the investigator's opinion and measurable disease (any of the following measurable lymph nodes ≥1.5 cm in the greatest transverse diameter and/or hepatomegaly or splenomegaly) and demonstration of CLL cells in the peripheral blood by flow cytometry
Exclusion Criteria:
* Subjects with known active central nervous system (CNS) involvement by malignancy. Those with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment with no evidence of symptomatic disease and stable abnormalities on repeat imaging.
* History of another primary malignancy that has not been in remission for at least 2 years. (The following are exempt from the 2-year limit: nonmelanoma skin cancer, completely resected stage 1 solid tumor with low risk for recurrence, curatively treated localized prostate cancer, cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear, and in situ breast cancer that has been completely resected.)
* Subjects with Richter's transformation
* Prior treatment with any gene therapy product
* Active hepatitis B, active hepatitis C, or active human immunodeficiency virus (HIV) infection
* Systemic fungal, bacterial, viral, or other infection that is not controlled
* Presence of acute or extensive chronic graft versus host disease (GVHD)
* History of any one of the following cardiovascular conditions within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease
* History or presence of clinically relevant CNS pathology such as epilepsy, generalized seizure disorder, aphasia, stroke with current neurologic sequelae, severe brain injuries, dementia, Parkinson's disease, cerebellar disease,cerebral edema, or psychosis
* Pregnant or nursing (lactating) women
* Use of any of the following medications or treatments within the noted time prior to leukapheresis:
• Alemtuzumab within 6 months prior to leukapheresis
• Allogeneic hematopoietic stem cell transplant within 100 days prior to leukapheresis
• Cladribine within 3 months prior to leukapheresis
• Donor lymphocyte infusions (DLI) within 2 months prior to leukapheresis
• Radiation including large bone marrow fields such as sternum or pelvis within 6 weeks prior to leukapheresis
• Fludarabine within 4 weeks prior to leukapheresis
• GVHD therapies such as calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolate mofetil, rapamycin, or immunosuppressive antibodies (such as anti-tumor necrosis factor-α \[TNFα\], anti-interleukin-6 \[IL-6\], or anti-interleukin-6 receptor \[IL 6R\]) within 4 weeks prior to leukapheresis
• Cyclophosphamide, ifosfamide, bendamustine, chlorambucil, or melphalan within 2 weeks prior to leukapheresis
• Therapeutic doses of corticosteroids (defined as \> 20 mg/day prednisone or equivalent) within 7 days prior to leukapheresis
• Anti-CD20 monoclonal antibodies within 7 days prior to leukapheresis
• Venetoclax within 4 days prior to leukapheresis
• Idelalisib or duvelisib within 2 days prior to leukapheresis
• Lenalidomide or covalent and non-covalent BTKi within 1 day prior to leukapheresis
• Experimental agents, including off-label use of approved drugs (with the exception of acalabrutinib which may be continued up to the day before leukapheresis), within 4 weeks prior to leukapheresis unless progression is documented on the experimental therapy and at least 3 half-lives have elapsed prior to leukapheresis * Uncontrolled medical, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol, as judged by the Investigator; or subject unwillingness or inability to follow the procedures required in the protocol * Progressive vascular tumor invasion, thrombosis, or embolism * Deep vein thrombosis or embolism not managed on a stable regimen of anticoagulation * Use of any of the following medications or treatments within the noted time prior to leukapheresis lenalidomide or acalabrutinib within 1 day prior to leukapheresis experimental agents, including off-label use of approved drugs, within 4 weeks prior to leukapheresis. * Venous thrombosis or embolism requiring treatment but not managed on a stable regimen of anticoagulation * For subjects in the venetoclax + JCAR017 combination cohorts only, concomitant treatment with CYP3A moderate/strong inducers or moderate/strong inhibitors which cannot be discontinued
BIOLOGICAL: JCAR017 (lisocabtagene maraleucel), BIOLOGICAL: JCAR017 (lisocabtagene maraleucel) + ibrutinib, BIOLOGICAL: JCAR017 (lisocabtagene maraleucel) + venetoclax
Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Small Lymphocytic
TRANSCEND_CLL_004
UT Southwestern
CA-4948-101: Open-Label, Dose Escalation and Expansion Trial of Emavusertib (CA-4948) in Relapsed or Refractory Primary Central Nervous System Lymphoma (R/R PCNSL)
This is a multi-center, open-label study to evaluate the safety, pharmacokinetics (PK), and anti-cancer activity of oral administration of emavusertib alone or in combination with ibrutinib in adult participants with relapsed or refractory (R/R) hematologic malignancies. This trial will be completed in four parts. In Part A1, emavusertib will be evaluated first in a dose escalating monotherapy setting to establish the safety and tolerability (complete). In Part A2, emavusertib will be evaluated in combination with ibrutinib at 560 milligrams (mg) once daily (QD) or 420 mg QD as indicated by disease (Part A2 complete). Part B will comprise 2 cohorts to assess safety and efficacy of emavusertib in combination with ibrutinib in participants with R/R primary central nervous system lymphoma (PCNSL) who have directly progressed on a bruton tyrosine kinase inhibitor (BTKi). In this part of the study, emavusertib will be dosed at 100 mg or 200 mg twice daily (BID) in combination with ibrutinib in 28-day treatment cycles. Part C will comprise 3 treatment arms in the second-line setting to assess the efficacy and safety of emavusertib monotherapy, ibrutinib monotherapy, and emavusertib in combination with ibrutinib in participants with R/R PCNSL who are naïve to BTKi treatment. In this part of the study, eligible second-line participants with R/R PCNSL who are naïve to BTKi treatment will be randomized 1:1:1 to 1 of 3 treatment arms: (1) emavusertib 200 mg BID, (2) ibrutinib 560 mg QD, or (3) emavusertib 200 mg BID in combination with ibrutinib 560 mg QD.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Praveen Ramakrishnan Geethakumari
ALL
18 Years and over
PHASE1
NCT03328078
STU-2021-0281
Inclusion Criteria:
• Males and females greater than or equal to 18 years of age
• Life expectancy of at least 3 months
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
• Histopathologically confirmed diagnosis of PCNSL (medical record is acceptable). Cerebral biopsies are not required if imaging reveals typical images of PCNSL.
• Participants with parenchymal lesions must have unequivocal evidence of disease progression (e.g., presence of at least 1 measurable target lesion \[≥ 10 millimeters (mm) and ≤ 40 mm in the longest diameter on brain magnetic resonance imaging \[MRI\] or head computed tomography \[CT\] on imaging within 28 days prior to Cycle 1 Day 1\]). In cases where the tumor size is smaller but still measurable and located at a critical central nervous system (CNS) location, disabling the participant and/or causing symptoms, this participant may be eligible following a discussion with the Sponsor Medical Monitor.
• For participants limited to leptomeningeal involvement, cerebrospinal fluid (CSF) analysis (cytology and/or flow cytometry) with or without additional imaging (MRI) of the spine as clinically indicated is required to document abnormal cells within 28 days prior to Cycle 1 Day 1. Exclusion Criteria for Part B and Part C
• Participants with only intraocular PCNSL without brain lesion or CSF involvement, T-cell lymphoma, systemic presence of lymphoma, or non-CNS lymphoma metastatic to the CNS
• Evidence of systemic lymphoma. This must be demonstrated by a positron emission tomography (PET) scan (or CT scan with contrast if applicable) of the chest, abdomen, and pelvis at Screening (testicular ultrasound may be considered to exclude a testicular lymphoma disseminated to the brain).
• Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) or prior history of systemic lymphoma, unless the participant has been free of the disease for ≥ 3 years.
• Active malignancy other than PCNSL requiring systemic therapy
• Previous BTKi treatment (Part C only).
• History of Grade ≥ 3 rhabdomyolysis without complete recovery
• Requirement for urgent therapy due to uncontrolled tumor mass/edema effects.
• Received external beam radiation therapy to the CNS within 28 days prior to Cycle 1 Day 1.
• Received prior investigational drugs (including treatment in clinical research, unapproved combination products, and new dosage forms) within 28 days or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1; allogeneic hematopoietic stem cell transplant (HSCT) within 60 days prior to Cycle 1 Day 1; or had clinically significant graft-versus-host disease (GVHD) requiring ongoing up-titration of immunosuppressive medications prior to Screening (with the exception of a BTKi for Part B only). Note: The use of a stable or tapering dose of immunosuppressive therapy post-HSCT and/or topical steroids for ongoing skin GVHD is permitted with Sponsor Medical Monitor approval
• Any prior systemic anti-cancer treatment such as chemotherapy, immunomodulatory drug therapy, etc., received within 14 days or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1 (with the exception of ibrutinib or other BTKi for Part B only, which may be continued until the day before Cycle 1 Day 1)
• Prior history of hypersensitivity or anaphylaxis to emavusertib, ibrutinib or any of their excipients.
DRUG: Emavusertib, DRUG: Ibrutinib
Relapsed Hematologic Malignancy, Refractory Hematologic Malignancy, Relapsed Primary Central Nervous System Lymphoma, Refractory Primary Central Nervous System Lymphoma, Non-Hodgkins Lymphoma
MYD88, IRAK4, NHL, PCNSL, Lymphoma, Neoplasms, Lymphoproliferative Disorders, Lymphatic Diseases, Immunoproliferative Disorders, Immune System Diseases, Lymphoma, Non-Hodgkin, Relapsed/refractory Central Nervous System (CNS) Lymphoma, Systemic Lymphoma with Concurrent CNS Lymphoma, Systemic Lymphoma with a History of Treated CNS Lymphoma, Ibrutinib, Bruton tyrosine kinase inhibitor (BTKi), Primary CNS Lymphoma
UT Southwestern
Intra-arterial Gemcitabine vs. IV Gemcitabine and Nab-Paclitaxel Following Radiotherapy for LAPC (TIGeR-PaC)
The study is a multi-center, open-label, randomized active controlled study of subjects with locally advanced pancreatic adenocarcinoma which is unresectable.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Salwan Al Mutar
ALL
18 Years and over
PHASE3
NCT03257033
STU-2022-0726
Inclusion Criteria:
• Histologically or Cytopathology confirmed pancreatic adenocarcinoma with initial diagnosis within 8 weeks of consent for patients who enroll at cycle 1, and from the start of cycle 1 of gemcitabine + nab-paclitaxel chemotherapy for patients who enroll at cycle 2
• Locally advanced, unresectable disease at screening and prior to randomization, as defined by NCCN criteria determined by an on-site, experienced, multidisciplinary team (as confirmed by CT or MRI within 30 days of the start of cycle 1)
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
• Age ≥ 18 years
• Adequate laboratory values prior to receiving the first dose of nab-paclitaxel and gemcitabine: (criterion must be met prior to cycle 2.) For a subject with elevated bilirubin, AST or ALT, who has had a biliary stent placed, if the subject's lab values have returned to within the required range for eligibility noted below in sub-criteria e and f \[(AST) ALT ≤ 3.0 X the upper normal limit, and total bilirubin ≤ 1.5 X the upper normal limit\] after placement of stent and prior to cycle 2, he/she is eligible for the study. Additional details regarding eligibility for subjects who have had biliary stents recently placed are outlined in sub-criteria f and h below.
• Absolute neutrophil count (ANC) ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Hemoglobin ≥ 9.0 g/dL
• Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 50 mL/min/1.73 m2 for subjects with creatinine \>1.5 mg/dL
• \*Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 X the upper normal limit of institution's normal range
• \*Total bilirubin ≤ 1.5 X the upper normal limit of institution's normal range -OR- If biliary stent is placed or planned to be placed within 6 weeks of Cycle 1 Day 1 (C1D1), total bilirubin ≤ 2.0 X the upper normal limit of institution's normal range (see section 9.1.4 for dose modification due to elevated bilirubin)
• Prothrombin time (PT) and partial thromboplastin time (PTT) must be ≤ 1.5 X upper normal limit of institution's normal range. Subjects who are currently taking anti-coagulant therapy are eligible if not meeting this criterion
• International normalized ration (INR) ≤ 1.5 X upper normal limit of institution's normal range. Subjects who are currently taking anti-coagulant therapy are eligible if not meeting this criterion \*For elevated AST, ALT, and total bilirubin at screening, subject must have a normalized result prior to initiation of Cycle 2 if abnormal labs are considered related to bile duct obstruction and a biliary stent has been placed
• Life expectancy \> 12 weeks
• Negative pregnancy test for women of childbearing potential (either serum or urine) within one day prior to administration of the first dose of chemotherapy. Women of childbearing potential should use highly effective methods of contraception during treatment and for up to 6 months following treatment cessation
• Provide written informed consent
• Subjects willing to participate in the study for at least 8 months if randomized to IA gemcitabine OR IV gemcitabine + nab-paclitaxel
Exclusion Criteria:
• Any prior treatment for pancreatic cancer OR more than one cycle of gemcitabine and nab-paclitaxel treatment. For subjects who have started on their first cycle of gemcitabine and nab-paclitaxel treatment prior to consent, Inclusion Criterion #1 only applies to the first gemcitabine and nab-paclitaxel dose and must be within 6 weeks of confirmed diagnosis
• Any evidence of metastatic disease or another active malignancy within the past one year except for cervical cancer in situ, in situ carcinoma of the bladder or non-melanoma carcinoma of the skin.
• Subjects unable or unwilling to have their first randomized treatment within 3 weeks of the post induction imaging and within 5 weeks of their last induction treatment
• Subjects without baseline tumor imaging
• As determined by the Sponsor: Arterial anatomy unsuitable for IA delivery of gemcitabine to the intended tumor site, determined by CT or MRI, as determined and approved by the Sponsor Imaging Advisor, which includes the following:
• Stenosis or occlusion in the intended artery for treatment
• Inability to exclude major side branches in the area of the intended RenovoCath® catheter occlusion
• No suitable artery with a diameter greater than 3 mm in proximity of at least one side of the tumor
• Superior mesenteric vein (SMV) occlusion or stenosis that cannot be resolved with medication or intervention prior to randomization, if the superior mesenteric artery (SMA) is the only viable treatment artery Note: Arterial Anatomy will be reviewed by the Sponsor, RenovoRx Imaging Advisor, and RenovoRx Medical Monitor for approval
• Contraindications for SBRT planning which includes the following:
• Gastrointestinal mucosal infiltration evident at the time of diagnostic endoscopy
• Prior abdominal radiotherapy judged to have clinically significant degree of overlap with planned SBRT dose distribution Note: Primary tumors with a diameter greater than 7 cm must be assessed on a case-by-case basis with the RenovoRx Imaging Advisor prior to excluding the subject from the trial.
• Subjects with known HIV infection or active viral hepatitis
• Severe infections requiring hospitalization within 4 weeks prior to the first study treatment, including but not limited to complications of infection, bacteremia or severe pneumonia
• Signs or symptoms of infection within 2 weeks prior to the first study treatment, as assessed by the Investigator
• Received antibiotics for treatment of an infection within 48 hours prior to initiation of study treatment. Subjects receiving prophylactic antibiotics are eligible
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to gemcitabine or nab-paclitaxel
• Any anti-cancer therapy including chemotherapy, hormonal therapy for prostate cancer, or radiotherapy within 2 weeks prior to initiation of study treatment; or herbal therapy intended as anti-cancer therapy within 1 week prior to initiation of study treatment
• Subjects with uncontrolled seizures
• Cardiovascular disease including unstable angina or life-threatening cardiac arrhythmia, myocardial infarction, stroke; or New York Heart Association (NYHA) Class III or IV congestive heart failure (CHF) within the last 3 months prior to the first study treatment. Subjects with prior history of Myocardial Infarction (MI), congestive heart failure (CHF), coronary artery bypass grafting, or prior valve surgery need to have assessment of ejection fraction (EF) to ensure EF is not ≤ 40% (as determined by MRI, ECHO, or Nuclear Scan), within the last 3 months prior to the initiation of study treatment
• Other severe concurrent disease or comorbidities which make it difficult to participate in this study, as assessed by Investigator
• Any of the following procedures prior to initiation of study treatment:
• Catheterization, endoscopy, stent or drain placement within 48 hours. (Diagnostic laparoscopy without surgical intervention and/or port placement do not require any wait time prior to study treatment)
• Minor surgery requiring light sedation (such as surgical laparoscopy) within 2 weeks
• Major surgery within 4 weeks
• Women who are breastfeeding
• Male or female subjects of reproductive potential who do not agree to either remain abstinent or employ highly effective and acceptable forms of contraception throughout their participation in the study and for 6 months after the last study treatment
• Subjects receiving any other investigational agents within 2 weeks prior to the initiation of treatment
• Any social situations or psychiatric illness that would limit compliance with study requirements
• Subjects unable or unwilling to have standard catheterization procedure
DRUG: Gemcitabine, DRUG: nab-paclitaxel, DEVICE: RenovoCath
Locally Advanced Pancreatic Cancer, Pancreas
UT Southwestern
Observation or Radiation Therapy in Treating Patients With Newly Diagnosed Grade II Meningioma That Has Been Completely Removed by Surgery
This randomized phase III trial studies how well radiation therapy works compared with observation in treating patients with newly diagnosed grade II meningioma that has been completely removed by surgery. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors.
Call 1-888-980-6050
canceranswerline@utsouthwestern.edu
Zabihullah Wardak
ALL
18 Years and over
PHASE3
NCT03180268
STU 122017-011
Inclusion Criteria:
* PRIOR TO STEP 1 REGISTRATION:
* The patient must have a newly diagnosed unifocal intracranial meningioma, gross totally resected, and histologically confirmed as WHO grade II based upon pathology findings at the enrolling institution. WHO grade will be assigned according to WHO 2016 criteria
* Gross total resection (GTR) will be interpreted as modified Simpson grade 1-3 without gross residual dural-based or extradural tumor. GTR must be confirmed both by modified Simpson grade and by post-operative magnetic resonance imaging (MRI) findings. The modified Simpson grade can be inferred from the operative report (surgeon does not need to explicitly describe the Simpson grade for the purposes of eligibility)
* Step 1 registration must occur within 180 days of the initial surgery; this will provide sufficient time for post-operative imaging confirmation of resection extent after resolution of operative changes. Moreover, it will permit additional surgery if needed to achieve a GTR. Within this 180 day interval, a second surgery is permitted in order to achieve GTR, but even with a second surgery, Step 1 registration must occur within 180 days of the initial resection
* GTR must be confirmed on post-operative imaging following the most recent surgery. For protocol enrollment, the assessment of GTR will be made at each site. However, submission of both pre-operative and post-operative MRIs is required for patients. If a second surgery is performed, submission of post-operative MRI is required and pre-operative MRI is required only if obtained. All sequences obtained in the pre- and post-operative MR imaging are to be submitted to National Radiology Group (NRG) Oncology for study registration. The post-operative MRI must be completed within sufficient time to permit step 1 registration within 180 days of the initial resection. These same conditions apply in the setting of a second surgical procedure, although if a second surgery is completed, step 1 registration must still occur with 180 days of initial surgery. Computed tomography (CT) imaging is not required, but may be obtained if desired clinically, for instance to assess calcifications or hyperostosis
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
* NOTE: Central pathology review must occur between steps 1 and 2 of registration. Once appropriate pathology specimens are received, central pathology review will occur within 10 business days, and must confirm WHO grade II meningioma before the patient can proceed to step 2 registration and randomization
* PRIOR TO STEP 2 REGISTRATION:
* Histologically confirmed diagnosis of WHO grade II meningioma confirmed by central pathology review prior to step 2 registration
* Age \>= 18
* History/physical examination, including neurologic examination within 60 days prior to step 2 registration
* Post-operative Zubrod performance status 0-1 within 60 days prior to step 2 registration
* If the patient is a woman is of childbearing potential, a serum pregnancy test, obtained within 14 days prior to step 2 registration, must be negative, and, if randomized to receive radiation therapy, the woman must agree to use contraception
Exclusion Criteria:
* Optic nerve sheath meningioma, spinal or other extracranial meningioma, multiple meningiomas, hemangiopericytoma
* Definitive evidence of metastatic meningioma (metastasis, although rare, can occur and is exclusionary)
* Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (carcinoma in situ of the breast, oral cavity, cervix, melanoma in situ, or other non-invasive malignancies are permissible)
* Previous radiotherapy to the scalp, cranium, brain, or skull base and radiation-induced meningiomas
* Major medical illnesses or psychiatric impairments, which in the investigators opinion, will prevent administration or completion of the protocol therapy and/or preclude informed consent; these include, but are not restricted to:
* Unstable angina and/or congestive heart failure requiring hospitalization at the time of step 2 registration
* Transmural myocardial infarction within the last 6 months prior to step 2 registration
* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of step 2 registration
* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 2 registration
* Type II neurofibromatosis (NF2)
* Ailments entailing substantial increases in sensitivity and side effect risk from radiation therapy (ataxia telangiectasia, Nijmegen breakage syndrome, and human immunodeficiency virus (HIV) with CD4 count \< 200 cells/microliter); HIV testing is not required for eligibility for this protocol, and known HIV positive patients are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count \>= 200 cells/microliter within 30 days prior to step 2 registration
* Inability to undergo MRI with and without contrast (e.g. claustrophobia, non-MRI compatible implant or foreign body, gadolinium allergy or renal dysfunction preventing the patient from receiving gadolinium- institutional guidelines should be used to determine if patients are at risk for renal dysfunction). Note that patients with severe claustrophobia are permitted on this study if they are willing and able to undergo MRI with adequate sedation or anesthesia PROCEDURE: Biospecimen Collection, OTHER: Clinical Observation, RADIATION: Intensity-Modulated Radiation Therapy, OTHER: Laboratory Biomarker Analysis, PROCEDURE: Magnetic Resonance Imaging, RADIATION: Proton Beam Radiation Therapy, OTHER: Quality-of-Life Assessment
Grade 2 Meningioma, Intracranial Meningioma
Testing the Addition of 131I-MIBG or Lorlatinib to Intensive Therapy in People With High-Risk Neuroblastoma (NBL)
This phase III trial studies iobenguane I-131 or lorlatinib and standard therapy in treating younger patients with newly-diagnosed high-risk neuroblastoma or ganglioneuroblastoma. Radioactive drugs, such as iobenguane I-131, may carry radiation directly to tumor cells and not harm normal cells. Lorlatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving iobenguane I-131 or lorlatinib and standard therapy may work better compared to lorlatinib and standard therapy alone in treating younger patients with neuroblastoma or ganglioneuroblastoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
ALL
365 Days to 30 Years old
PHASE3
NCT03126916
STU 052018-099
Inclusion Criteria:
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patients must be enrolled on ANBL00B1 (NCT00904241) or APEC14B1 (NCT02402244) prior to enrollment on ANBL1531 (NCT03126916)
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patient must be \>= 365 days and =\< 30 years of age at diagnosis
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; the following disease groups are eligible:
* Patients with International Neuroblastoma Risk Group (INRG) stage M disease are eligible if found to have either of the following features:
* MYCN amplification (\> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR
* Age \> 547 days regardless of biologic features
* Patients with INRG stage MS disease with MYCN amplification
* Patients with INRG stage L2 disease with MYCN amplification
* Patients \> 547 days of age initially diagnosed with INRG stage L1, L2 or MS disease who progressed to stage M without prior chemotherapy may enroll within 4 weeks of progression to stage M
* Patients \>= 365 days of age initially diagnosed with MYCN amplified INRG stage L1 disease who progress to stage M without systemic therapy may enroll within 4 weeks of progression to stage M
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patients initially recognized to have high-risk disease must have had no prior systemic therapy (other than topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing); patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high risk disease but subsequently found to meet the criteria will also be eligible; patients who receive localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis will be eligible
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a serum creatinine based on age/sex as follows:
* 1 to \< 2 years: male = 0.6; female = 0.6
* 2 to \< 6 years: male = 0.8; female = 0.8
* 6 to \< 10 years: male = 1; female = 1
* 10 to \< 13 years: male = 1.2; female = 1.2
* 13 to \< 16 years: male = 1.5; female = 1.4
* \>= 16 years: male = 1.7; female = 1.4
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age, and
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 10 x ULN; for the purposes of this study, ULN for SGPT (ALT) is 45
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \> 50% by echocardiogram or radionuclide angiogram
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: No known contraindication to peripheral blood stem cell (PBSC) collection; examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): See ANBL2131 (NCT06172296) protocol for eligible high-risk neuroblastoma diagnoses
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): In addition, all patients transferring from ANBL2131 (NCT06172296) to ANBL1531 (NCT03126916) Arm E must have tumors with an ALK aberration
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Given the lack of data with lorlatinib in infant populations, patients transferring from ANBL2131 (NCT06172296) to ANBL1531 (NCT03126916) must be \> 1 year of age at time of transfer to ANBL1531 (NCT03126916). Patients \< 1 year of age found to have a qualifying ALK alteration as part of ANBL2131 (NCT06172296) may continue to participate in ANBL2131 (NCT06172296)
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients initially recognized to have high-risk disease must have received no more than one cycle of topotecan/cyclophosphamide either after enrollment to ANBL2131 (NCT06172296) or started emergently prior to enrollment to ANBL2131 (NCT06172296)
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients may have received up to one cycle of intermediate risk chemotherapy prior to initial enrollment to ANBL2131 (NCT06172296)
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients may have received localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): In order to facilitate patient transfer and ensure timely distribution of lorlatinib, there are no blood count requirements to meet at time of transfer from ANBL2131 (NCT06172296) to ANBL1531 ((NCT03126916) Arm E. Note the blood count criteria that must be met prior to start of Induction cycle 2 on Arm E. Lorlatinib therapy should start no sooner than day 1 of Induction cycle 2
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): No known irreversible grade 2 or greater atrioventricular (AV) block
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Due the potential psychiatric risks from lorlatinib, patients should not have a personal history of a serious psychiatric disorder requiring pharmacologic intervention or severe enough to be considered life-threatening
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): No known contraindication to PBSC collection. Examples of contraindications might be a weight or size less than the collecting institution deems feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure
Exclusion Criteria:
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patients with INRG stage L2 tumors without amplification of MYCN regardless of tumor histology (may meet criteria for high risk classification but are not eligible for this trial)
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patients with bone marrow failure syndromes
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patients for whom targeted radiopharmaceutical therapy would be contraindicated due to underlying medical disorders
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Lactating females who plan to breastfeed their infants
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients who have previously received treatment with lorlatinib or other ALK inhibitor
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients who have undergone treatment arm randomization callback or started induction cycle 2 on ANBL2131 (NCT06172296)
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients who have an INRG Stage L2 tumor without amplification of MYCN regardless of tumor histology (may meet criteria for high risk classification but are not eligible for this trial)
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients with bone marrow failure syndromes
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Lactating females who plan to breastfeed their infants
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation PROCEDURE: Autologous Hematopoietic Stem Cell Transplantation, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration and Biopsy, DRUG: Busulfan, DRUG: Carboplatin, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, DRUG: Dexrazoxane Hydrochloride, BIOLOGICAL: Dinutuximab, DRUG: Doxorubicin Hydrochloride, PROCEDURE: Echocardiography Test, DRUG: Etoposide Phosphate, RADIATION: External Beam Radiation Therapy, RADIATION: Iobenguane I-123, RADIATION: Iobenguane I-131, DRUG: Isotretinoin, DRUG: Lorlatinib, PROCEDURE: Magnetic Resonance Imaging, DRUG: Melphalan Hydrochloride, PROCEDURE: Multigated Acquisition Scan, PROCEDURE: Positron Emission Tomography, BIOLOGICAL: Sargramostim, PROCEDURE: Therapeutic Conventional Surgery, DRUG: Thiotepa, DRUG: Topotecan Hydrochloride, DRUG: Vincristine Sulfate
Ganglioneuroblastoma, Ganglioneuroblastoma, Nodular, Neuroblastoma, Brain and Nervous System
Children’s Health
A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements (TRIDENT-1)
Phase 1 dose escalation will determine the first cycle dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD), the biologically effective dose and recommended Phase 2 dose (RP2D) of repotrectinib given to adult subjects with advanced solid malignancies harboring an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement. Midazolam DDI substudy will examine effect of of repotrectinib on CYP3A induction. Phase 2 will determine the confirmed Overall Response Rate (ORR) as assessed by Blinded Independent Central Review (BICR) of repotrectinib in each subject population expansion cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement. The secondary objective will include the duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and clinical benefit rate (CBR) of repotrectinib in each expansion cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
ALL
12 Years and over
PHASE1
NCT03093116
STU-2019-1323
PHASE 1
Key
• Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary CNS tumors) (Stage IV, American Joint Committee on Cancer v.7) that harbors an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement by protocol specified tests.
• ECOG PS 0-1.
• Age ≥18 (or age ≥ 20 of age as required by local regulation).
• Capability to swallow capsules intact (without chewing, crushing, or opening).
• At least 1 measurable target lesion according to RECIST version 1.1. CNS-only measurable disease as defined by RECIST version 1.1 is allowed.
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• Patients with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
• Baseline laboratory values fulfilling the following requirements:Absolute neutrophils count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine clearance Within normal limits or \> 40 mL/min; Total serum bilirubin \< 1.5 × ULN; Liver transaminases (ASTs/ALTs) \< 2.5 × ULN; \< 5 × ULN if liver metastases are present Alkaline phosphatase (ALP); \< 2.5 × ULN; \< 5 × ULN if liver and/or bone metastasis are present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without supplementation
• Life expectancy ≥ 3 months. PHASE 2 Key Inclusion Criteria
• Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary CNS tumors) that harbors a ROS1, or NTRK1-3 gene fusion.
• Subject must have a documented ROS1 or NTRK1-3 gene fusion determined by tissue-based local testing using either:
• a next-generation sequencing (NGS) or quantitative polymerase chain reaction (qPCR) test will be accepted to determine molecular eligibility. • Adequate tumor tissue needs to be sent to the Sponsor designated central diagnostic laboratory for retrospective confirmation by a central diagnostic laboratory test selected by the Sponsor. OR
• a fluorescence in situ hybridization (FISH) test AND prospective confirmation of fusion status by a central diagnostic laboratory test selected by the Sponsor PRIOR to enrollment will be accepted to determine molecular eligibility. * Adequate tumor tissue must be sent to the Sponsor designated central diagnostic laboratory for prospective confirmation by a central diagnostic laboratory test selected by the Sponsor PRIOR to enrollment.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
• Age ≥12 (or age ≥ 20 as required by local regulation).
• Willing and able to provide written institutional review board (IRB)/institutional ethics committee-approved Informed Consent or an Assent signed by a parent or legal guardian for subjects age 12 to 17.
• At least 1 measurable target lesion according to RECIST (v1.1) prospectively confirmed by Blinded Independent Central Radiology Review (BICR), selected by Sponsor, PRIOR to enrollment. Subjects with CNS-only measurable disease ≥10 mm as defined by RECIST (v1.1) are eligible.
• Subjects with advanced solid tumors harboring ROS1, NTRK1, NTRK2, or NTRK3 rearrangement will be assigned into 6 distinct expansion (EXP) cohorts provided all inclusion and exclusion criteria are met. i. EXP-1: ROS1 TKI-naïve ROS1+ NSCLC ii. EXP-2: 1 Prior ROS1 TKI and 1 Platinum based chemo ROS1+ NSCLC iii. EXP-3: 2 Prior ROS1 TKIs ROS1+ NSCLC (No Chemo or IO) iv. EXP-4: 1 Prior ROS1 TKI ROS1+ NSCLC (No Chemo or IO) v. EXP-5: TRK TKI-naïve NTRK+ solid tumors vi. EXP-6: TRK TKI-pretreated NTRK+ solid tumors
• Subjects with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
• Baseline laboratory values fulfilling the following requirements:Absolute neutrophils count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine clearance \> 40 mL/min; Total serum bilirubin \< 1.5 × ULN; Liver transaminases (ASTs/ALTs) \< 2.5 × ULN; \< 5 × ULN if liver metastases are present Alkaline phosphatase (ALP); \< 2.5 × ULN; \< 5 × ULN if liver and/or bone metastasis are present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without supplementation
• Life expectancy ≥ 3 months. Key Exclusion Criteria PHASE 1 and PHASE 2
• Concurrent participation in another therapeutic clinical trial.
• Symptomatic brain metastases or leptomeningeal involvement.
• History of previous cancer, except for squamous cell or basal-cell carcinoma of the skin, or any in situ carcinoma that has been completely resected, requiring therapy within the previous 2 years.
• Major surgery within 4 weeks of start of repotrectinib treatment. Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry. Palliative radiation (≤10 fractions) must have been completed at least 48 hours prior to study entry
• Clinically significant cardiovascular disease (either active or within 6 months prior to enrollment): myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association Classification Class ≥ II), cerebrovascular accident or transient ischemic attack, symptomatic bradycardia, requirement for anti-arrhythmic medication. Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2
• Any of the following cardiac criteria: Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTcF) \> 470 msec obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \> 250 msec) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval.
• Known active infections (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• Peripheral neuropathy of CTCAE ≥grade 2.
• History of extensive, disseminated, bilateral, or presence of CTCAE grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis. Subjects with history of prior radiation pneumonitis are not excluded.
Inclusion Criteria:
• Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary CNS tumors) (Stage IV, American Joint Committee on Cancer v.7) that harbors an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement by protocol specified tests.
• ECOG PS 0-1.
• Age ≥18 (or age ≥ 20 of age as required by local regulation).
• Capability to swallow capsules intact (without chewing, crushing, or opening).
• At least 1 measurable target lesion according to RECIST version 1.1. CNS-only measurable disease as defined by RECIST version 1.1 is allowed.
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• Patients with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
• Baseline laboratory values fulfilling the following requirements:Absolute neutrophils count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine clearance Within normal limits or \> 40 mL/min; Total serum bilirubin \< 1.5 × ULN; Liver transaminases (ASTs/ALTs) \< 2.5 × ULN; \< 5 × ULN if liver metastases are present Alkaline phosphatase (ALP); \< 2.5 × ULN; \< 5 × ULN if liver and/or bone metastasis are present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without supplementation
• Life expectancy ≥ 3 months. PHASE 2 Key Inclusion Criteria
• Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary CNS tumors) that harbors a ROS1, or NTRK1-3 gene fusion.
• Subject must have a documented ROS1 or NTRK1-3 gene fusion determined by tissue-based local testing using either:
• a next-generation sequencing (NGS) or quantitative polymerase chain reaction (qPCR) test will be accepted to determine molecular eligibility. • Adequate tumor tissue needs to be sent to the Sponsor designated central diagnostic laboratory for retrospective confirmation by a central diagnostic laboratory test selected by the Sponsor. OR
• a fluorescence in situ hybridization (FISH) test AND prospective confirmation of fusion status by a central diagnostic laboratory test selected by the Sponsor PRIOR to enrollment will be accepted to determine molecular eligibility. * Adequate tumor tissue must be sent to the Sponsor designated central diagnostic laboratory for prospective confirmation by a central diagnostic laboratory test selected by the Sponsor PRIOR to enrollment.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
• Age ≥12 (or age ≥ 20 as required by local regulation).
• Willing and able to provide written institutional review board (IRB)/institutional ethics committee-approved Informed Consent or an Assent signed by a parent or legal guardian for subjects age 12 to 17.
• At least 1 measurable target lesion according to RECIST (v1.1) prospectively confirmed by Blinded Independent Central Radiology Review (BICR), selected by Sponsor, PRIOR to enrollment. Subjects with CNS-only measurable disease ≥10 mm as defined by RECIST (v1.1) are eligible.
• Subjects with advanced solid tumors harboring ROS1, NTRK1, NTRK2, or NTRK3 rearrangement will be assigned into 6 distinct expansion (EXP) cohorts provided all inclusion and exclusion criteria are met. i. EXP-1: ROS1 TKI-naïve ROS1+ NSCLC ii. EXP-2: 1 Prior ROS1 TKI and 1 Platinum based chemo ROS1+ NSCLC iii. EXP-3: 2 Prior ROS1 TKIs ROS1+ NSCLC (No Chemo or IO) iv. EXP-4: 1 Prior ROS1 TKI ROS1+ NSCLC (No Chemo or IO) v. EXP-5: TRK TKI-naïve NTRK+ solid tumors vi. EXP-6: TRK TKI-pretreated NTRK+ solid tumors
• Subjects with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
• Baseline laboratory values fulfilling the following requirements:Absolute neutrophils count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine clearance \> 40 mL/min; Total serum bilirubin \< 1.5 × ULN; Liver transaminases (ASTs/ALTs) \< 2.5 × ULN; \< 5 × ULN if liver metastases are present Alkaline phosphatase (ALP); \< 2.5 × ULN; \< 5 × ULN if liver and/or bone metastasis are present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without supplementation
• Life expectancy ≥ 3 months. Key Exclusion Criteria PHASE 1 and PHASE 2
• Concurrent participation in another therapeutic clinical trial.
• Symptomatic brain metastases or leptomeningeal involvement.
• History of previous cancer, except for squamous cell or basal-cell carcinoma of the skin, or any in situ carcinoma that has been completely resected, requiring therapy within the previous 2 years.
• Major surgery within 4 weeks of start of repotrectinib treatment. Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry. Palliative radiation (≤10 fractions) must have been completed at least 48 hours prior to study entry
• Clinically significant cardiovascular disease (either active or within 6 months prior to enrollment): myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association Classification Class ≥ II), cerebrovascular accident or transient ischemic attack, symptomatic bradycardia, requirement for anti-arrhythmic medication. Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2
• Any of the following cardiac criteria: Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTcF) \> 470 msec obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \> 250 msec) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval.
• Known active infections (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• Peripheral neuropathy of CTCAE ≥grade 2.
• History of extensive, disseminated, bilateral, or presence of CTCAE grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis. Subjects with history of prior radiation pneumonitis are not excluded.
DRUG: Oral repotrectinib (TPX-0005)
Locally Advanced Solid Tumors, Metastatic Solid Tumors, Colon, Liver, Lung/Thoracic, Pancreas, Rectum, Stomach
ALK, ROS1, NTRK, Sarcoma, Lung Neoplasms, Carcinoma, NSCL, NSCLC, Non Small Cell Lung, Thyroid Disease, Colonic Neoplasms, Thyroid Neoplasms, Carcinoma, Neuroendocrine, Respiratory Tract Neoplasms, Thoracic Neoplasms, Neoplasms by Site, Neoplasms, Lung Disease, Respiratory Tract Disease, Carcinoma, Bronchogenic, Bronchial Neoplasms, Endocrine System Disease, Colorectol Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Gastrointestinal Disease, Colonic Disease, Intestinal Disease, Endocrine Gland Neoplasms, Head and Neck Neoplasms, Neuroendocrine Tumors, Neuroectodermal Tumors, Neoplasms, Germ Cell and Embryonal, Neoplasms by Histologic Type, Adenocarcinoma, Non Small Cell Lung Cancer, Solid Tumors, Rearrangements, TRIDENT-1, TKI, TKI naive, TKI pretreated, Anti-tumor activity, Repotrectinib, Advanced Solid Malignancies
UT Southwestern; Parkland Health & Hospital System
Active Surveillance, Bleomycin, Etoposide, Carboplatin or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors
This phase III trial studies how well active surveillance help doctors to monitor subjects with low risk germ cell tumors for recurrence after their tumor is removed. When the germ cell tumor has spread outside of the organ in which it developed, it is considered metastatic. Chemotherapy drugs, such as bleomycin, carboplatin, etoposide, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. The trial studies whether carboplatin or cisplatin is the preferred chemotherapy to use in treating metastatic standard risk germ cell tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Jonathan Wickiser
ALL
Not specified
PHASE3
NCT03067181
STU 052017-035
Inclusion Criteria:
* There is no age limit for the low risk stratum (stage I ovarian immature teratoma and stage I non-seminoma or seminoma malignant GCT \[all sites\])
* Standard risk 1: Patients must be \< 11 years of age at enrollment
* Standard risk 2: Patients must be \>= 11 and \< 25 years of age at enrollment
* Patients enrolling on one of the low risk arms must be newly diagnosed with a stage I germ cell tumor; for the standard risk arms, patients must be newly diagnosed with malignant germ cell tumor (stage II or higher).
* Histologic confirmation of a primary extracranial germ cell tumor in any of the categories outlined below is required of all patients at enrollment , with the following exceptions:
* Among patients were initially diagnosed with completely resected non-seminoma malignant GCT and later recur during observation post surgery, a diagnostic biopsy is not required for enrollment if elevated tumor markers rise to \> 5 x upper limit of normal (ULN) on at least 2 measurements taken at least 1 week apart. The pathology report of initial surgery should be provided
* Patients may be enrolled without histologic or cytologic confirmation in the rare case where there are exceptionally raised tumor markers (alpha fetoprotein \[AFP- ≥ 500 ng/mL or HCG ≥ 500 IU/L) and radiologic features consistent with GCT. In addition, the treating clinician must deem that the patient's tumor is not suitable for upfront resection and that a biopsy is not in the patient's best interest; or that there is a need to start therapy urgently
* Low risk immature teratoma (IT); site: ovarian; stage: any; grade: any; histology: pure immature teratoma, mixed immature and mature teratoma, (may contain microscopic foci of yolk sac tumor \[\< 3 mm\], but no other pathological evidence of MGCT); tumor markers: alpha-FP =\< 1,000 ng/mL, beta-HCG institutional normal; all ages
* Low risk stage I non-seminoma MGCT; site: ovarian, testicular, or extragonadal; stage: COG stage I, FIGO stage IA and IB, American Joint Committee on Cancer (AJCC) testicular stage IA, IB and IS; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or mixed); all ages
* Low risk stage I seminoma-MGCT; site: testicular; stage: COG stage I; AJCC testicular stage IA IB, and IS; histology: must contain only seminoma; may contain immature/mature teratoma; may NOT contain yolk sac tumor, embryonal carcinoma, or choriocarcinoma; all ages
* Standard risk 1 (SR1); site: ovarian, testicular, or extragonadal; stage: COG stage II-IV, FIGO stage IC-IV, (International Germ Cell Consensus Classification \[IGCCC\] criteria DO NOT apply); histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) \< 11
* Standard risk 2 (SR2)
* Site: ovarian; stage: COG stage II, III, and III-X, FIGO stage IC, II and III; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) \>= 11 and \< 25
* Site: testicular; stage: COG stage II-IV, AJCC stage II, III, IGCCC good risk; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma: must be IGCCC good risk; post op: alpha-FP \< 1,000 ng/mL, beta-HCG \< 5,000 IU/mL and lactate dehydrogenase (LDH) \< 3.0 x normal; age (years) \>= 11 and \< 25
* Notes:
* IGCCC criteria only apply to SR2 patients with a testicular primary tumor
* Use post-op tumor marker levels to determine IGCCC risk group
* Pure seminoma patients are not eligible for the standard risk arms of the study
* For the low risk stage I non-seminoma MGCT and the standard risk arms, components of yolk sac tumor, embryonal carcinoma, or choriocarcinoma can be mixed with other forms of GCT, such as seminoma or mature or immature teratoma; if yolk sac tumor is the only malignant component present, then it must be deemed by the pathologist to be greater than a "microscopic component" of yolk sac tumor
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, 2 or 3; use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Organ function requirements apply ONLY to patients who will receive chemotherapy (SR1 and SR2 patients)
* Adequate renal function defined as:
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 (within 7 days prior to enrollment) OR
* A serum creatinine based on age/sex as follows (within 7 days prior to enrollment): (mg/dL)
* 1 month to \< 6 months male: 0.4 female: 0.4
* 6 months to \< 1 year male: 0.5 female: 0.5
* 1 to \< 2 years male: 0.6 female: 0.6
* 2 to \< 6 years male: 0.8 female: 0.8
* 6 to \< 10 years male: 1 female: 1
* 10 to \< 13 years male: 1.2 female: 1.2
* 13 to \< 16 years: male: 1.5 female: 1.4
* \>= 16 years male: 1.7 female: 1.4
* Total bilirubin =\< 2 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
* Unless due to Gilbert's disease, malignant involvement of liver or vanishing bile duct syndrome
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 x upper limit of normal (ULN) (within 7 days prior to enrollment)
* Unless due to Gilbert's disease, malignant involvement of liver or vanishing bile duct syndrome
* Peripheral absolute neutrophil count (ANC) \>= 750/mm\^3 (within 7 days prior to enrollment) AND
* Platelet count \>= 75,000/mm\^3 (within 7 days prior to enrollment)
* Patients enrolling on the standard risk arms must be medically fit to receive protocol treatment and with no contraindications to protocol treatment
* Eligibility criteria to participate in the pilot study of the AYA-Hears instrument (patient reported outcomes \[PROs\] of ototoxicity) Note: participants in group 1 will not receive AGCT1531 protocol-directed therapy; all other AYA-HEARS patients must be enrolled on the AGCT1531 SR2 arm in order to participate
* \>= 11 and \< 25 years old at enrollment
* Able to fluently speak and read English
* Has received prior cisplatin- or carboplatin-based chemotherapy regimen for malignancy including diagnoses other than germ cell tumor
* Followed for cancer or survivorship care at one of the following institutions:
* Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
* Dana Farber/Harvard Cancer Center
* Hospital for Sick Children
* Children's Hospital of Eastern Ontario
* Oregon Health and Science University
* Seattle Children's Hospital
* Yale University
Exclusion Criteria:
* Patients with any diagnoses not listed including:
* Stage I testicular cancer patients who have undergone primary RPLND (retroperitoneal lymph node dissection)
* Pure ovarian or extragonadal dysgerminoma/seminoma
* Pure mature teratoma
* Pure immature teratoma with alpha-fetoprotein (AFP) \>= 1000 ng/mL
* "Poor risk" GCT (age \>= 11 years old and COG stage IV ovarian, COG stage II- IV extragonadal, or IGCCC intermediate or poor risk testicular), or
* Primary central nervous system (CNS) germ cell tumor
* Germ cell tumor with somatic malignant transformation
* Spermatocytic seminoma
* Patients must have had no prior systemic therapy for the current cancer diagnosis
* Patients must have had no prior radiation therapy with the exception of CNS irradiation of brain metastases; (this exception only applies to SR1 patients; any patients over age 11 with distant metastases to brain \[stage IV disease\] would be considered poor risk and therefore not eligible for this trial)
* Patients with significant, pre-existing co-morbid respiratory disease that contraindicate the use of bleomycin are ineligible for the standard risk arms of the trial
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential; (this criteria applies ONLY to patients who will receive chemotherapy \[SR1 and SR2 patients\])
* Lactating females who plan to breastfeed their infants; (this criteria applies ONLY to patients who will receive chemotherapy \[SR1 and SR2 patients\])
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation; (this criteria applies ONLY to patients who will receive chemotherapy \[SR1 and SR2 patients\]) OTHER: Best Practice, PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, BIOLOGICAL: Bleomycin Sulfate, DRUG: Carboplatin, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Etoposide, PROCEDURE: Magnetic Resonance Imaging, OTHER: Pharmacogenomic Study, PROCEDURE: Pulmonary Function Test, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration
Childhood Extracranial Germ Cell Tumor, Extragonadal Embryonal Carcinoma, Germ Cell Tumor, Malignant Germ Cell Tumor, Malignant Ovarian Teratoma, Stage I Ovarian Choriocarcinoma, Stage I Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage I Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage I Testicular Choriocarcinoma AJCC v6 and v7, Stage I Testicular Embryonal Carcinoma AJCC v6 and v7, Stage I Testicular Seminoma AJCC v6 and v7, Stage I Testicular Yolk Sac Tumor AJCC v6 and v7, Stage II Ovarian Choriocarcinoma, Stage II Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage II Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage II Testicular Choriocarcinoma AJCC v6 and v7, Stage II Testicular Embryonal Carcinoma AJCC v6 and v7, Stage II Testicular Yolk Sac Tumor AJCC v6 and v7, Stage III Ovarian Choriocarcinoma, Stage III Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage III Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage III Testicular Choriocarcinoma AJCC v6 and v7, Stage III Testicular Embryonal Carcinoma AJCC v6 and v7, Stage III Testicular Yolk Sac Tumor AJCC v6 and v7, Stage IV Ovarian Choriocarcinoma, Stage IV Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage IV Ovarian Yolk Sac Tumor AJCC v6 and v7, Testicular Mixed Choriocarcinoma and Embryonal Carcinoma, Testicular Mixed Choriocarcinoma and Teratoma, Testicular Mixed Choriocarcinoma and Yolk Sac Tumor, Other Female Genital, Other Male Genital, Ovary, Unknown Sites
UT Southwestern; Children’s Health; Parkland Health & Hospital System
Inotuzumab Ozogamicin in Treating Younger Patients With B-Lymphoblastic Lymphoma or Relapsed or Refractory CD22 Positive B Acute Lymphoblastic Leukemia
This phase II trial studies how well inotuzumab ozogamicin works in treating younger patients with B-lymphoblastic lymphoma or CD22 positive B acute lymphoblastic leukemia that has come back (relapsed) or does not respond to treatment (refractory). Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers ozogamicin to kill them.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
ALL
1 Year to 21 Years old
PHASE2
NCT02981628
STU 062017-028
Inclusion Criteria:
* Patients must be \>= 1 year and \< 22 years of age at the time of enrollment
* Patients must have B-ALL, or previously diagnosed B lymphoblastic lymphoma (B-LL), with \>= 5% (M2 or M3) bone marrow blasts with or without extramedullary disease
* NOTE: Relapsed patients previously diagnosed with B-lymphoblastic lymphoma (B-LL) are eligible if they have an M2 or M3 marrow at the time of enrollment on this study
* Patients with ALL or B-LL who have M2 morphology must have local confirmatory testing showing \>= 5% blasts by flow cytometry, fluorescence in situ hybridization (FISH) testing or other molecular method
* Leukemic blasts must demonstrate surface expression of CD22 at the time of relapse by local/institutional flow cytometry of a bone marrow aspirate sample; (assessment of CD22 using a bright fluorophore such as phycoerythrin \[PE\] is strongly recommended)
* In the case of an inadequate aspirate sample (dry tap) or if bone marrow aspirate is unable to be performed due to patient clinical status, flow cytometry of peripheral blood specimen may be substituted if the patient has at least 1,000/uL circulating blasts; alternatively, CD22 expression may be documented by immunohistochemistry of a bone marrow biopsy specimen
* Patients with one of the following:
* Second or greater relapse;
* Primary refractory disease with at least 2 prior induction attempts;
* First relapse refractory to at least one prior re-induction attempt
* Any relapse after HSCT (Cohort 1 ONLY)
Patients with Down syndrome are eligible ONLY for Cohort 1 with:
* Any of above disease status, OR
* First relapse with no prior re-induction attempt NOTE: Patients with Down syndrome or prior HSCT are NOT eligible for Cohort 2 combination therapy
* Patients with Philadelphia chromosome (Ph)+ ALL must have had two prior therapy attempts including two different tyrosine kinase inhibitors (TKIs)
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy, defined as resolution of all such toxicities to =\< grade 2 or lower per the inclusion/exclusion criteria prior to entering this study. Apply to Cohort 2:
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment.
* A waiting period prior to enrollment is not required for patients receiving standard cytotoxic maintenance chemotherapy (i.e., corticosteroid, vincristine, 6MP, and/or methotrexate).
* A waiting period is not required for patients receiving a single dose of intrathecal methotrexate, hydrocortisone, and/or cytarabine within 7 days prior to enrollment
* \>= 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy. For patients who previously received calaspargase pegol, \>= 21 days must have elapsed after the last dose. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy.
* Note: Cytoreduction with hydroxyurea must be discontinued \>= 24 hours prior to the start of protocol therapy.
* Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment.
* Anti-cancer agents that are antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1. There is an exception for blinatumomab infusions, for which patients must have been off for at least 3 days and all drug related toxicity must have resolved to grade 2 or lower as outlined in the inclusion/exclusion criteria.
* Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid. A waiting period prior to enrollment is not required for patients receiving corticosteroid for leukemia therapy/cytoreduction.
* Radiotherapy: \>= 2 weeks must have elapsed since local palliative radiation therapy (XRT) (small port); \>= 3 months must have elapsed if prior cranial or craniospinal XRT was received, if \>= 50% of the pelvis was irradiated, or if total body irradiation (TBI) was received; \>= 6 weeks must have elapsed if other substantial bone marrow irradiation was given.
* Stem cell transplant or rescue without TBI: For Cohort 1, at least 90 days must have elapsed since stem cell transplant and at least 30 days from donor lymphocyte infusion. Patient must have had no more than one previous HSCT and currently have no evidence of active graft vs. host disease (GVHD). For Cohort 2, no prior HSCT is allowed.
* Chimeric antigen receptor (CAR) T cell therapy: At least 30 days must have elapsed from the last CAR-T cell infusion
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or
* A serum creatinine based on age/gender as follows:
* 1 to \< 2 years: maximum serum creatinine 0.6 mg/dL (both male and female)
* 2 to \< 6 years: maximum serum creatinine 0.8 mg/dL (both male and female)
* 6 to \< 10 years: maximum serum creatinine 1 mg/dL (both male and female)
* 10 to \< 13 years: maximum serum creatinine 1.2 mg/dL (both male and female)
* 13 to \< 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female)
* \>= 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female)
* Direct bilirubin =\< 1.5 x upper limit of normal (ULN) for age, and
* Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 5 x ULN for age; for the purpose of this study, the ULN for ALT will be 45 U/L
Exclusion Criteria:
* Patients with any prior history of SOS irrespective of severity
* Patients with isolated central nervous system (CNS), testicular, or any other extramedullary site of relapse
* Patients who have been previously treated with inotuzumab ozogamicin
* Patients who have previously received HSCT (Cohort 2 only)
* Patients with Down syndrome (Cohort 2 only)
* History of allergic reaction attributed to compounds of similar or biologic composition to inotuzumab ozogamicin or other agents in the study
* Note: Patients with history of allergy to pegaspargase/calaspargase pegol are eligible for enrollment on Cohort 2 if Erwinia formulation of asparaginase can be obtained
* Patients with active optic nerve and/or retinal involvement are not eligible; patients who are presenting with visual disturbances should have an ophthalmologic exam and, if indicated, a magnetic resonance imaging (MRI) to assess optic nerve or retinal involvement
* Patients who are currently receiving another investigational drug
* Patients who are currently receiving or plan to receive other anti-cancer agents (except hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy, and intrathecal chemotherapy)
* Anti-GVHD or agents to prevent organ rejection post-transplant; patients who are receiving cyclosporine, tacrolimus, or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial; at least 3 half-lives must have elapsed after the last dose of GVHD or anti-rejection medications
* Patients who are currently receiving or plan to receive corticosteroids except as described below
* Systemic corticosteroids may be administered for cytoreduction up to 24 hours prior to the start of protocol therapy, (Cohort 1 only) for all patients, corticosteroids may be administered as a premedication for inotuzumab ozogamicin and as treatment for allergic reactions or for physiologic replacement/stress dosing of hydrocortisone for documented adrenal insufficiency; corticosteroids are not allowed for other indications
* Patients with known human immunodeficiency virus (HIV), hepatitis B or C infections; testing to prove negative status is not required for enrollment unless it is deemed necessary for usual medical care of the patient
* Patients who have an active uncontrolled infection defined as:
* Positive bacterial blood culture within 48 hours of study enrollment;
* Fever above 38.2 degree Celsius (C) within 48 hours of study enrollment with clinical signs of infection; fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability
* A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection
* Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection as long as cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved; for patients with clostridium (C.) difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline
* Active viral or protozoal infection requiring IV treatment
* Patients known to have one of the following concomitant genetic syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Schwachman (Schwachman-Diamond-Blackfan) syndrome or any other known bone marrow failure syndrome
* There have been no human studies of inotuzumab ozogamicin in pregnant women and no reports of exposure in utero; based on nonclinical safety studies, inotuzumab ozogamicin has the potential to impair human male and female fertility and to adversely affect human embryo fetal development; women of childbearing potential should be advised to avoid becoming pregnant while receiving inotuzumab ozogamicin; there is no information regarding the presence of inotuzumab ozogamicin in human milk, the effects on the breast-fed infant, or the effects on milk production; because of the potential for adverse reactions in breast-fed infants, women should not breast-feed during treatment with inotuzumab ozogamicin and for at least 2 months after the final dose
* Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained within 7 days prior to enrollment
* Female patients who are sexually active and of reproductive potential are not eligible unless they agree to use an effective contraceptive method for the duration of their study participation and for 8 months after the last dose of inotuzumab ozogamicin
* Men with female partners of childbearing potential should use effective contraception during treatment with inotuzumab ozogamicin and for at least 5 months after the last dose of inotuzumab ozogamicin
* Lactating females are not eligible unless they agree not to breastfeed their infants DRUG: Asparaginase Erwinia chrysanthemi, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration and Biopsy, DRUG: Calaspargase Pegol, DRUG: Cyclophosphamide, DRUG: Cytarabine, PROCEDURE: Diagnostic Imaging, BIOLOGICAL: Inotuzumab Ozogamicin, DRUG: Leucovorin Calcium, PROCEDURE: Lumbar Puncture, DRUG: Methotrexate, DRUG: Pegaspargase, DRUG: Vincristine
Recurrent B Acute Lymphoblastic Leukemia, Recurrent B Lymphoblastic Lymphoma, Refractory B Acute Lymphoblastic Leukemia, Refractory B Lymphoblastic Lymphoma, Leukemia, Other
Children’s Health
Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III-IVA Squamous Cell Carcinoma of the Head and Neck Who Have Undergone Surgery
This phase II trial studies how well radiation therapy with or without cisplatin works in treating patients with stage III-IVA squamous cell carcinoma of the head and neck who have undergone surgery. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known if radiation therapy is more effective with or without cisplatin in treating patients with squamous cell carcinoma of the head and neck.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Sher
ALL
18 Years and over
PHASE2
NCT02734537
STU 072016-020
Inclusion Criteria:
* PRE-REGISTRATION (STEP 0)
* Pathologically proven diagnosis of squamous cell carcinoma (including variants such as verrucous carcinoma, spindle cell carcinoma, carcinoma not otherwise specified \[NOS\]) of the head/neck (oral cavity, oropharynx, hypopharynx or larynx); pathologic stage III or IVA (American Joint Committee on Cancer \[AJCC\] 8): T3-T4a, N0-3, M0 or T1-T2, N1-3, M0
* Patient has undergone total resection of the primary tumor with curative intent
* NOTE: Patient is to be pre-registered to screening (Step 0) and tissue submitted to Foundation Medicine as soon as possible after surgery in order to meet the 8 week deadline to register the patient to Step 1 after surgery; full assay minimum turn-around time is 17-24 days
* For oropharynx primary tumors, the patient must have negative human papillomavirus (HPV) status of the tumor as determined by p16 protein expression using immunohistochemistry (IHC)
* Patients with, per the operative and/or pathology report, positive margin(s) (tumor present at the cut or inked edge of the tumor) which is not superceded by an additional margin of tumor-negative tissue, nodal extracapsular extension, and/or gross residual disease after surgery are not eligible
* A paraffin-embedded surgical tumor tissue specimen has been located is available for shipment to Foundation Medicine, Inc. following pre-registration
* NOTE: Complete the EA3132-specific FoundationOne requisition form
* Patients with a history of a curatively treated malignancy must be disease-free for at least two years except for carcinoma in situ of cervix and/or non-melanomatous skin cancer; patients must not have received chemotherapy or investigational therapy within two years of surgical resection of the primary tumor
* Patient must not have had previous irradiation to the head and neck that would result in overlap in radiation fields for the current disease
* Patients with recurrent disease or multiple primaries are ineligible
* RANDOMIZATION (STEP 1)
* NOTE: Patient must meet all eligibility criteria outlined in pre-registration; patient may not be randomized until site has been notified that the central determination of p53 mutation status of the surgical tumor tissue has been completed and site has been notified of assay completion
* Per the operative report, the gross total resection of the primary tumor with curative intent was completed within 8 weeks prior to randomization
* The patient must have the following assessments done =\< 8 weeks prior to randomization:
* Examination by a head and neck surgeon
* Chest x-ray (or chest computed tomography \[CT\] scan or CT/positron emission tomography \[PET\] of the chest or magnetic resonance imaging \[MRI\]) to rule out distant metastatic disease
* Patient has Eastern Cooperative Oncology Group (ECOG) performance status 0-1 within 2 weeks prior to randomization
* Women must not be pregnant or breast-feeding; females of childbearing potential must have a blood or urine study within 2 weeks prior to randomization to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study and until 60 days from the last study treatment
* Absolute neutrophil count \>= 1,500/mm\^3 within 4 weeks prior to randomization
* Platelets \>= 100,000/mm\^3 within 4 weeks prior to randomization
* Total bilirubin =\< the upper limit of normal (ULN) within 4 weeks prior to randomization
* Calculated creatinine clearance must be \> 60 ml/min using the Cockcroft-Gault formula within 4 weeks prior to randomization
* Patient must not have an intercurrent illness likely to interfere with protocol therapy DRUG: Cisplatin, RADIATION: Intensity-Modulated Radiation Therapy, OTHER: Laboratory Biomarker Analysis
Head and Neck Squamous Cell Carcinoma, Hypopharyngeal Squamous Cell Carcinoma, Laryngeal Squamous Cell Carcinoma, Laryngeal Squamous Cell Carcinoma, Spindle Cell Variant, Lip and Oral Cavity Squamous Cell Carcinoma, p16INK4a Negative Oropharyngeal Squamous Cell Carcinoma, Stage III Hypopharyngeal Carcinoma AJCC v8, Stage III Laryngeal Cancer AJCC v8, Stage III Lip and Oral Cavity Cancer AJCC v8, Stage III Oral Cavity Verrucous Carcinoma, Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8, Stage IVA Hypopharyngeal Carcinoma AJCC v8, Stage IVA Laryngeal Cancer AJCC v8, Stage IVA Lip and Oral Cavity Cancer AJCC v8, Stage IVA Oral Cavity Verrucous Carcinoma, Stage IVA Oropharyngeal (p16-Negative) Carcinoma AJCC v8
Neuroblastoma Maintenance Therapy Trial (NMTT)
Difluoromethylornithine (DFMO) will be used in an open label, single agent, multicenter, study for patients with neuroblastoma in remission. In this study subjects will receive 730 Days of oral difluoromethylornithine (DFMO) at a dose of 750 mg/m2 ± 250 mg/m2 BID (strata 1, 2, 3, and 4) OR 2500 mg/m2 BID (stratum 1B) on each day of study. This study will focus on the use of DFMO in high risk neuroblastoma patients that are in remission as a strategy to prevent recurrence.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
All
1 Year to 30 Years old
Phase 2
NCT02679144
STU 022016-028
Inclusion Criteria:
• All patients must have a pathologically confirmed diagnosis of neuroblastoma, < 30.99 years of age and classified as high risk at the time of diagnosis. Exception: patients who are initially diagnosed as non-high-risk neuroblastoma, but later converted (and/or relapsed) to high risk neuroblastoma are also eligible.
• All patients must be in complete remission (CR):
• No evidence of residual disease on scan
• No evidence of disease metastatic to bone marrow.
• Specific Criteria by Stratum: Stratum 1/1B: All patients must have completed standard upfront therapy that replicates treatment which patients who were enrolled on ANBL0032 received, including: intensive induction chemotherapy and (if feasible) resection of primary tumor, followed by: consolidation with high-dose chemotherapy with stem cell transplant and radiotherapy, followed by: immunotherapy with Ch14.18/IL-2/GM-CSF (dinutuximab) and retinoic acid;. All subjects on Stratum 1/B must have also met the following criteria: • A pre-transplant disease status evaluation that met International Neuroblastoma Response Criteria (INRC) for CR (complete response), VGPR (very good partial response), or PR (partial response) for primary site, soft tissue metastases and bone metastases. Patients who meet those criteria must also meet the protocol-specified criteria for bone marrow response prior to transplant as outlined below: No more than 10% tumor involvement (based on total nucleated cellular content) seen on any specimen from a bilateral bone marrow aspirate/biopsy. Stratum 2: Neuroblastoma that is in first complete remission following standard upfront therapy different from that described for Stratum 1. Stratum 3: Neuroblastoma that failed to have a response of at least PR following induction chemotherapy and surgical resection of the primary tumor, but that has achieved CR following additional therapy. Stratum 4: Patients who have achieved a second or subsequent CR following relapse(s).
• Pre-enrollment tumor survey: Prior to enrollment on this study, a determination of mandatory disease staging must be performed:
• Tumor imaging studies including
• Bilateral bone marrow aspirates and biopsy
• This disease assessment is required for eligibility and preferably should be done within 2 weeks prior to enrollment, but must be done within a maximum of 4 weeks before enrollment.
• Timing from prior therapy: Stratum 1/1B: Enrollment no later than 60 days after completion of upfront therapy, (last dose of cis-retinoic acid) with a maximum of 6 cycles of cis-retinoic acid maintenance therapy. Stratum 2, 3 and 4: Enrollment no later than 60 days from last dose of the most recent therapy.
• Patients must have a Lansky or Karnofsky Performance Scale score of > 50% and patients must have a life expectancy of ≥ 2 months.
• All clinical and laboratory studies for organ functions to determine eligibility must be performed within 7 days prior to enrollment unless otherwise indicated below.
• Patients must have adequate organ functions at the time of registration:
• Hematological: Total absolute phagocyte count ≥1000/μL
• Liver: Subjects must have adequate liver function
• Renal: Adequate renal function
• Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method. Female patients who are lactating must agree to stop breast-feeding.
• Written informed consent in accordance with institutional and FDA (food and drug administration) guidelines must be obtained from all subjects (or patients' legal representative).
Exclusion Criteria:
• BSA (Body Surface Area) of <0.25 m2.
• Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.
• Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from hematological and bone marrow suppression effects of prior chemotherapy.
• Infection: Subjects who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.
• Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.
Drug: Difluoromethylornithine (DFMO)
Neuroblastoma, Brain and Nervous System
Children’s Health
Safety and Efficacy Study in Recurrent or Progressive Grade III or IV IDH1 Mutated Glioma
This multi-site, Phase 1/2a clinical trial is an open-label study to identify the safety, pharmacokinetics, and efficacy of a repeated dose regimen of NEO100 (perillyl alcohol) for the treatment of patients with radiographically-confirmed progression of Grade IV glioma or recurrent primary or secondary Grade IV glioma. The study will have two phases, Phase 1 and Phase 2a. Phase 1 is a standard cohort dose escalation 3+3 design used to determine the maximum tolerated dose for Phase 2a. There will be up to 24 patients enrolled in Phase 1. There will be 25 patients enrolled in Phase 2a. For both phases of the study, NEO100 will be self-administered four times daily for a 28-day treatment cycles until disease progression, death or patient withdraw from study for any reason, whichever occurs first. Version 10 of the protocol changed the inclusion criteria for Phase 2a to limit inclusion to those patients with progressive or recurrent primary or secondary Grade IV gliomas expressing IDH1 mutations. Prior to the protocol amendment, 4 patients were enrolled who were IDH1 wild-type. Therefore, an additional 28 patients will be recruited for a total of 32 patients enrolled into Phase 2a of this study to have 35 evaluable cases. Version 12 of the protocol expanded the inclusion criteria for Phase 2a to include those patients with progressive or recurrent Grade III Astrocytoma expressing IDH1 mutations. Review of the literature specific to these patients found the same expected time to progression and death. As a result, the number of patients to enroll remains 32 to have 35 evaluable cases.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Michael Youssef
ALL
18 Years to old
PHASE1
NCT02704858
STU-2024-1208
o Inclusion Criteria
• To be eligible to participate in the study, a patient must meet all of the following inclusion criteria:
Patient must:
* Have radiographically-confirmed progression of, or recurrent, primary or
* secondary Grade IV glioma, including infratentorial (brainstem, cerebellar) glioma (confirmed by biopsy) and subcortical glioma.
* Have radiographically-confirmed progression of, recurrent, primary or secondary Grade III astrocytoma.
* All patients must be on a stable or decreasing dose of steroids for at least five days prior to the date of informed consent.
Patient must have failed previous radiation treatment or combined treatment with temozolomide and radiation.
If progression of disease occurs within 90 days of conformal radiation, the progression/recurrence must be outside of the radiation field or proven by biopsy/resection.
Patient must be ≥ 18 years of age. Patient must have an ECOG performance status of 0-2 or KPS ≥ 60 (the latter for Phase 1 only).
Patient must have an expected survival of at least three months. Patient must have a baseline MRI with gadolinium within 14 days of first administration of study drug.
Patient must be willing to provide blood samples for pharmacokinetic study. If patient suffers from seizures, (s)he must be controlled on a stable dose of anti- epileptics for 14 days prior to the date of informed consent.
Patient must have adequate organ and marrow function as defined below:
* Absolute neutrophil count ≥ 1,500/mcL
* Platelets ≥ 100,000/mcL
* Total bilirubin within normal institutional limits
* AST (SGOT)/ALT (SPGT)≤ 2.5 × institutional upper limit of normal
* Creatinine within normal institutional limits Female patients of child-bearing potential and male patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for 30 days prior to the first administration of study drug, for the duration of study participation, and for 90 days following completion of therapy. Should a female patient become pregnant, or suspect she is pregnant, while participating in this study, she should inform her treating physician immediately.
* A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12
* consecutive months).
* A negative serum pregnancy test will be required of all female patients of child-bearing potential within seven days prior to initiating study drug.
* A serum pregnancy test will be repeated immediately if pregnancy is suspected. Patient must have the ability to understand, and the willingness to sign, a written informed consent.
* Phase 2a
* In addition to meeting Inclusion Criteria for the Phase I portion of the study, patients eligible for participation in the Phase 2a portion of the study must additionally meet the following
* criteria: Patients must have a confirmed IDH1 mutation by reverse transcription polymerase chain reaction (rtPCR) or immunohistochemistry (unless continuing into the Phase 2a portion of the study from the Phase I portion of the study).
o Exclusion Criteria
* If the patient meets any of the following criteria, the patient must not be enrolled:
The size of the tumor is \> 30mm (length x width), as assessed at the baseline (pre- study) MRI evaluation.
The tumor is multi-focal, as assessed at the baseline (pre-study) MRI evaluation.
Patient has completed chemo-radiation within the last 90 days prior to first administration of study drug, unless new contrast enhancement is outside of radiation field, or there is tissue proven recurrence or progression.
Patient has had surgery within seven days prior to the date of informed consent.
Patient has had any form of anti-cancer therapy or treatment within 28 days prior to first administration of study drug.
Patient has not recovered from adverse events due to chemotherapy,
• immunotherapy, or radiation therapy administered more than 28 days prior to first administration of study drug.
Patient has had prior treatment with bevacizumab, a chemotherapy wafer implant (Gliadel®), or any other FDA-approved anti-cancer therapy or treatment except temozolomide.
Patient has had more than one recurrence or progression of his/her tumors. Patient has received any other investigational agents within 28 days prior to the first administration of study drug.
Patient has had prior treatment with perillyl alcohol, administered either intravenously or intranasally.
Patient has a history of allergic reactions attributed to perillyl alcohol. Patient has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Patient must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
Patient has a history of new diagnosis or treatment of cancer other than malignant glioma within five years prior to the date of informed consent, except for basal cell carcinoma or squamous cell carcinoma of the skin.
Leptomeningeal involvement of the patient's tumor.
DRUG: Perillyl alcohol
Glioblastoma Multiforme, Brain and Nervous System
recurrent glioblastoma, recurrent GBM
UT Southwestern
Stereotactic Radiosurgery (SRS) Dose-Escalation Study for Brain Metastasis (SRS)
SRS dose escalation for brain metastases in radiation-naïve patients will establish true tolerable doses, which may exceed the current standard doses. This may lead to an improvement in local control, patient survival, and/or quality-of life.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Robert Timmerman
ALL
18 Years and over
NA
NCT02645487
STU 022015-106
Inclusion Criteria
• Biopsy-proven non-hematopoietic malignancy, except for small cell lung cancer, germ cell cancer, or unknown primary tumor.
• Radiographic evidence by MRI (or by CT scan with CT contrast if ineligible or intolerant of MRI) of brain metastasis. (If patient is unable to tolerate MRI contrast, an MRI without contrast is acceptable if lesions are visible)
• All brain metastases must be outside the brain stem (midbrain, pons and medulla).
• Patient must have 10 or less brain metastases.
• The maximum diameter of any lesion must be less than or equal to 3.0 cm.
• Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any targeted agents are allowed provided that: * Radiation was not to the brain. * Surgery to the brain was \> 7 days prior to SRS and there remains at least one additional brain metastasis that can be targeted with SRS
• Age ≥ 18 years.
• ECOG Performance Score of 2 or better/Karnofsky Performance Status score of 50-60 or better.
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria
• Patients had craniotomy and surgery to the brain within 7 days from the date of SRS.
• Patients with leptomeningeal metastasis. NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion.
• Patients with a contraindication to both MRI (with or without contrast) and CT scan (with contrast)
• Patients with life expectancy \< 3 months.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing at the time of SRS treatment due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Biopsy-proven non-hematopoietic malignancy, except for small cell lung cancer, germ cell cancer, or unknown primary tumor.
• Radiographic evidence by MRI (or by CT scan with CT contrast if ineligible or intolerant of MRI) of brain metastasis. (If patient is unable to tolerate MRI contrast, an MRI without contrast is acceptable if lesions are visible)
• All brain metastases must be outside the brain stem (midbrain, pons and medulla).
• Patient must have 10 or less brain metastases.
• The maximum diameter of any lesion must be less than or equal to 3.0 cm.
• Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any targeted agents are allowed provided that: * Radiation was not to the brain. * Surgery to the brain was \> 7 days prior to SRS and there remains at least one additional brain metastasis that can be targeted with SRS
• Age ≥ 18 years.
• ECOG Performance Score of 2 or better/Karnofsky Performance Status score of 50-60 or better.
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria
• Patients had craniotomy and surgery to the brain within 7 days from the date of SRS.
• Patients with leptomeningeal metastasis. NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion.
• Patients with a contraindication to both MRI (with or without contrast) and CT scan (with contrast)
• Patients with life expectancy \< 3 months.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing at the time of SRS treatment due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
RADIATION: Stereotactic Radiosurgery
Brain Neoplasms, Adult, Malignant, Brain and Nervous System, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Female, Breast - Male, Cardiovascular, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Eye and Orbit, Gall Bladder, Head and Neck, Hodgkins Lymphoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Lymphoid Leukemia, Lymphoma, Melanoma, skin, Multiple Myeloma, Nose, Other, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Sarcoma, Small Intestine, Soft Tissue, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva
UT Southwestern; Parkland Health & Hospital System
Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas
This phase II trial studies how well vismodegib, focal adhesion kinase (FAK) inhibitor GSK2256098, and capivasertib work in treating patients with meningioma that is growing, spreading, or getting worse (progressive). Vismodegib, FAK inhibitor GSK2256098, capivasertib, and abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
studyfinder@utsouthwestern.edu
ALL
18 Years and over
PHASE2
NCT02523014
* Documentation of disease:
* Histologic documentation: histologically proven intracranial meningioma as documented by central pathology review
* Molecular documentation: Presence of SMO, PTCH1, NF2, CDKN2A, AKT1, PIK3CA, PTEN mutations, CDKN2A copy number loss, CDK4, CDK6, CCND1, CCND2, CCND3, or CCNE1 copy number gain in tumor sample as documented specifically by the central laboratory, regardless of whether prior genotype testing outside of the central laboratory was performed
* Progressive OR residual disease, as defined by the following:
* Residual measurable disease: residual measurable disease immediately after surgery without requirement for progression; for grade I disease, progression pre-operatively needs to be documented, with an increase in size of the measurable primary lesion on imaging by 25% or more (bidirectional area); the change must occur between scans separated by no more than 25 months; for patients with SMO/PTCH1 mutations enrolling to receive vismodegib, the change can occur between scans separated by up to 25 months; residual measurable disease will be defined by bidimensionally measurable lesions with clearly defined margins by MRI scans, with a minimum diameter of 10 mm in both dimensions
* Progressive measurable disease: progression defined as an increase in size of the measurable primary lesion on imaging by 25% or more (bidirectional area); the change must occur between scans separated by no more than 25 months
* Post radiation patients: patients with measurable and progressive meningioma who have received radiation are potentially eligible, but need to show evidence of progressive disease after completion of radiation; if the progressive meningioma lesion has been radiated, at least 24 weeks must have elapsed from completion of radiation to registration; if the progressive lesion is outside of the radiation field, then an interval of at least 2 weeks must have elapsed from completion of radiation to registration
* Measurable disease: measurable disease is defined by a bidimensionally measurable main lesion on MRI or computed tomography (CT) images (MRI preferred) with clearly defined margins and a minimum diameter of 10 mm in both dimensions; multifocal disease is allowed
* Prior treatment
* Prior medical therapy is allowed but not required
* No limit on number of prior therapies
* No chemotherapy, or other investigational agents within 28 days prior to registration
* No other concurrent investigational agents or other meningioma-directed therapy (chemotherapy, radiation) while on study; additionally, no cases of nitrosourea or mitomycin C within 6 weeks prior to registration
* For patients treated with external beam radiation, interstitial brachytherapy or radiosurgery, an interval \> 4 weeks must have elapsed from completion of radiation therapy to registration; if the progressive lesion is outside of the radiation field, then an interval of at least 2 weeks must have elapsed from completion of radiation to registration
* Steroid dosing stable for at least 4 days
* Recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or less toxicity from other agents with exception of alopecia and fatigue
* No craniotomy 28 days prior to and after registration
* Not pregnant and not nursing:
\* A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
* For patients with NF2/CDKN2A/AKT1/PIK3CA/PTEN mutation, CKDN2A copy number loss, or CDK4/CDK6/CCND1/CCND2/CCND3/CCNE1 copy number gain: Age \>= 18 years
* For patients with SMO/PTCH1 mutation: Age \>= 30 years
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
* Patient history:
* Patients with history of neurofibromatosis (NF) may have other stable central nervous system (CNS) tumors (schwannoma, acoustic neuroma or ependymoma) if lesions have been stable for 6 months
* No metastatic meningiomas (as defined by extracranial meningiomas outside of CNS) allowed; spinal meningiomas are allowed
* No history of allergic reactions attributed to compounds of similar or biologic composition to assigned study drug
* No known active hepatitis B or C
* No current Child Pugh class B or C liver disease
* No uncontrolled gastric ulcer disease (grade 3 gastric ulcer disease within 28 days of registration)
* No uncontrolled hypertension defined as blood pressure (BP) \> 140/90
* No abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 28 days prior to registration
* No major surgery within 28 days prior to registration for any patients with AKT1/PIK3CA/PTEN mutations receiving capivasertib
* For patients going on to receive capivasertib (i.e. enrolled after Update #08)
* Patients should not have any of the following cardiac criteria:
* Any clinically important abnormalities in rhythm, conduction, or morphology of resting electrocardiogram (EKG) (e.g., complete left bundle branch block, third degree heart block)
* Any factors that increase the risk of corrected QT (QTc) prolongation or risk of arrhythmic events such as heart failure, hypokalemia, potential for Torsade de Pointes, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age, or any concomitant medication known to prolong the QT interval
* Experience any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association (NYHA) class \>= II
* Uncontrolled hypertension (systolic blood pressure \[SBP\] \< 90 mmHg and/or diastolic blood pressure \[DBP\] \< 50 mmHg)
* Cardiac ejection fraction outside institutional range of normal or \< 50% (whichever is higher) as measured by echocardiogram (or multigated acquisition \[MUGA\] scan if an echocardiogram can't be performed or is inconclusive); left ventricular ejection fraction (LVEF) below lower limit of normal for site
* Patients should not have any of the following criteria:
* With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of registration
* Hemoglobin \< 9 g/dL (\< 5.59 mmol/L); note: any blood transfusion must be \>= 14 days prior to the determination of a hemoglobin \>= 9 g/dL (\>= 5.59 mmol/L)
* Proteinuria 3+ on dipstick analysis or \> 500 mg/24 hours
* Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of capivasertib
* History of hypersensitivity to active or inactive excipients of capivasertib or drugs with a similar chemical structure or class to capivasertib
* Current disease or condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
* Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
* Previous allogeneic bone marrow transplant
* Known immunodeficiency syndrome
* Concomitant medications (only regarding NF2/CDKN2A/CDK4/CDK6/CCND1/CCND2/CCND3/CCNE1/AKT1/PIK3CA/PTEN genetic alterations):
* Chronic concomitant treatment with strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors must discontinue the drug for 14 days prior to registration on the study for patients with NF2 mutation enrolled to GSK2256098, as well as for patients with AKT1/PIK3CA/PTEN mutations enrolled to capivasertib
* For NF2 patients going on to receive GSK2256098 and for patients with AKT1/PIK3CA/PTEN mutations enrolled to capivasertib: concomitant treatment with strong CYP3A4 inducers or CYP2D6 substrates is not allowed; patients must discontinue the drug 14 days prior to registration
* For NF2 patients going on to receive abemaciclib: avoid concomitant use of CYP3A inducers and strong CYP3A inhibitors; use caution with coadministered moderate or weak CYP3A inhibitors
* Diabetic status:
* For patients with NF2 or SMO/PTCH1 mutations: No uncontrolled diabetes defined as a known diabetic with HBA1C \> 7.5 OR fasting glucose \> 140 mg/dL.
* For patients with AKT1/PIK3CA/PTEN mutations:
* Glycosylated hemoglobin (HbA1C) \< 8.0% (63.9 mmol/mol)
* No type 1 diabetes mellitus
* No requirement for insulin for routine diabetic management and control
* No requirement for more than two oral hypoglycemic medications for routine diabetic management and control
* Patients with a pre-existing diagnosis of type 2 diabetes mellitus must have fasting glucose \< 9.3 mmol/L (167mg/dL); fasting is defined as no caloric intake for at least 8 hours
* Patients without a pre-existing diagnosis of type 2 diabetes mellitus must have fasting glucose =\< 7.0 mmol/L (126 mg/dL); fasting is defined as no caloric intake for at least 8 hours
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Creatinine OR =\< 1.5 mg/dl x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance \> 50 mL/min
* Urine protein:creatinine ratio (UPC) =\< 45 mg/mmol
* Total bilirubin =\< 1.5 x upper limit of normal (ULN); except in case of Gilbert's disease
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x ULN
* Sodium, potassium, total calcium (corrected for serum albumin) \& phosphorus within normal limits per institutional guidelines
* QTcF \< 450 msec (QT calculated using Fridericia formula)
* Mean resting heart rate (determined from EKG) 50-100 beats per minute (BMP) (must be obtained from 12-lead EKG defined by a triplicate EKG for patients assigned to the capivasertib arm; patients assigned to all other arms will require a single EKG
* No uncontrolled medical comorbidities per investigator discretion (e.g. interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or pre-existing Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea)
* ADDITIONAL REGISTRATION ELIGIBILITY CRITERIA FOR ABEMACICLIB ARM: Hemoglobin \>= 8 g/dL
\* Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator; initial treatment must not begin earlier than the day after the erythrocyte transfusion
* ADDITIONAL REGISTRATION ELIGIBILITY CRITERIA FOR ABEMACICLIB ARM: Prior Treatment
* Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events \[CTCAE\] grade =\< 1) from the acute effects of chemotherapy except for residual alopecia or grade 2 peripheral neuropathy prior to registration; a washout period of at least 28 days is required between last chemotherapy dose and registration (provided the patient did not receive radiotherapy)
* Patients who received adjuvant radiotherapy must have completed and fully recovered from the acute effects of radiotherapy; a washout period of at least 28 days is required between end of radiotherapy and registration
* ADDITIONAL REGISTRATION ELIGIBILITY CRITERIA FOR ABEMACICLIB ARM: No active bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]); screening is not required for enrollment in the absence of symptoms
* ADDITIONAL REGISTRATION ELIGIBILITY CRITERIA FOR ABEMACICLIB ARM: No personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest
DRUG: Vismodegib, DRUG: FAK Inhibitor GSK2256098, DRUG: Capivasertib, DRUG: Abemaciclib
Intracranial Meningioma, Recurrent Meningioma, NF2 Gene Mutation
JoLT-Ca Sublobar Resection (SR) Versus Stereotactic Ablative Radiotherapy (SAbR) for Lung Cancer (STABLE-MATES)
To Determine if SAbR improves survival over SR in High Risk Operable Stage I NSCLC
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Robert Timmerman
ALL
18 Years and over
PHASE3
NCT02468024
STU 022015-069
• 0 Inclusion Criteria
• 1 Age \> 18 years.
• 2 ECOG/Zubrod performance status (PS) 0, 1, or 2 (reference Appendix C).
• 3 Radiographic findings consistent with non-small cell lung cancer, including lesions with ground glass opacities with a solid component of 50% or greater.
• 4 The primary tumor in the lung must be biopsy confirmed non-small cell lung cancer within 180 days prior to randomization.
• 5 Tumor ≤ 4 cm maximum diameter, including clinical stage IA and selected IB by PET or PET integrated with a simultaneous CT scan (PET-CT) of the chest and upper abdomen performed within 180 days prior to randomization (reference Appendix A \& B). Repeat imaging within 90 days prior to randomization is recommended for re-staging but is not required based on institutional norms.
• 6 All clinically suspicious mediastinal N1, N2, or N3 lymph nodes (\> 1 cm short-axis dimension on CT scan and/or positive on PET scan) confirmed negative for involvement with NSCLC by one of the following methods: mediastinoscopy, anterior mediastinotomy, EUS/EBUS guided needle aspiration, CT-guided, video-assisted thoracoscopic or open lymph node biopsy within 180 days of randomization.
• 7 Tumor verified by a thoracic surgeon to be in a location that will permit sublobar resection.
• 8 Tumor located peripherally within the lung. NOTE: Peripheral is defined as not touching any surface within 2 cm of the proximal bronchial tree in all directions. See bronchial tree diagram below. Patients with non-peripheral (central) tumors are NOT eligible.
• 9 No evidence of distant metastases.
• 10 Availability of pulmonary function tests (PFTs - spirometry, DLCO, +/- arterial blood gases) within 180 days prior to registration. Patients with tracheotomy, etc, who are physically unable to perform PFTs (and therefore cannot be tested for the Major criteria in 3.1.11 below) are potentially still eligible if a study credentialed thoracic surgeon documents that the patient's health characteristics would otherwise have been acceptable for eligibility as a high risk but nonetheless operable patient (in particular be eligible for sublobar resection).
• 11 To define eligibility of patients being at high risk for surgery, certain criteria must be met. Any one (1) of the following major criteria will define the high risk status for eligibility: Major Criteria * FEV1 ≤ 50% predicted (pre-bronchodilator value) * DLCO ≤ 50% predicted (pre-bronchodilator value) * Study credentialed thoracic surgeon believes the patient is potentially operable but that a lobectomy or pneumonectomy would be poorly tolerated by the patient for tangible or intangible reasons. The belief must be declared and documented in the medical record prior to randomization. If any of the major criteria are met, the patient is eligible based on high risk for surgery and minor criteria do not need to be considered. However, if no major criteria is met, at least two (2) minor criteria being met will also define eligibility for meeting the high risk status. Any two (2) of the following minor criteria will define the high risk status for eligibility: * Minor Criteria * Age ≥75 * FEV1 51-60% predicted (pre-bronchodilator value) * DLCO 51-60% predicted (pre-bronchodilator value) * Pulmonary hypertension (defined as a pulmonary artery systolic pressure greater than 40mm Hg) as estimated by echocardiography or right heart catheterization * Poor left ventricular function (defined as an ejection fraction of 40% or less) * Resting or Exercise Arterial pO2 ≤ 55 mm Hg or SpO2 ≤ 88% * pCO2 \> 45 mm Hg * Modified Medical Research Council (MMRC) Dyspnea Scale ≥ 3.
• 12 No prior intra-thoracic radiation therapy for previously identified intra-thoracic primary tumor (e.g. previous lung cancer) on the ipsilateral side. NOTE: Previous radiotherapy as part of treatment for head and neck, breast, or other non-thoracic cancer is permitted to the ipsilateral side so long as possible radiation fields would not overlap. NOTE: Radiotherapy to the contralateral lung is allowed so long as it was completed more than 3 years prior to randomization and there is no overlap of radiation fields.
• 13 Previous chemotherapy, radiotherapy, or surgical resection specifically for the lung cancer being treated on this protocol is NOT permitted.
• 14 No prior lung resection on the ipsilateral side.
• 15 Non-pregnant and non-lactating. Women of child-bearing potential must have a negative urine or serum pregnancy test prior to registration. Peri-menopausal women must be amenorrheic \> 12 months prior to registration to be considered not of childbearing potential.
• 16 No prior invasive malignancy, unless disease-free for ≥ 3 years prior to registration (exceptions: non-melanoma skin cancer, in-situ cancers).
• 17 Ability to understand and sign a written informed consent.
• 0 Exclusion Criteria
• 1 Age \<18
• 2 ECOG/Zubrod performance status (PS) greater than 3.
• 3 Radiographic findings with ground glass opacities and less than 50% solid component will be excluded.
• 4 The primary tumor in the lung, biopsy confirmed non-small cell lung cancer greater than 180 days prior to randomization.
• 5 Tumor \> 5 cm maximum diameter, including clinical stage IA and selected IB by PET or PET integrated with a simultaneous CT scan (PET-CT) of the chest and upper abdomen and/or performed greater than 180 days prior to randomization.
• 6 Lymph node biopsy greater than 180 days prior to randomization.
• 7 Thoracic surgeon confirms unable to remove tumor with sublobar resection.
• 8 Tumor located non-peripheral (central) region of lung (see bronchial tree diagram in 3.1.8).
• 9 Evidence of distant metastases.
• 10 Pulmonary function test (PFT - spirometry, DLCO, +/- arterial blood gases) greater than 180 days prior to registration. Patients physically unable to perform PFT's, such as patients with tracheotomy, that do not have written documentation from study credentialed thoracic surgeon stating eligibility.
• 11 Patients that do not meet either Major criteria or Minor criteria.
• 12 Prior intra-thoracic radiation therapy on ipsilateral side. Radiotherapy to the contralateral lung completed less than 3 years prior to randomization, with radiation field overlap.
• 13 Prior chemotherapy, radiotherapy, or surgical resection specifically for the lung cancer being treated on this protocol.
• 14 Prior lung resection on the ipsilateral side.
• 15 Pregnant and lactating women.
• 16 Prior invasive malignancy and less than 3 years disease free prior to registration (unless non-melanoma skin cancer, in-situ cancers).
• 17 Unable to understand and/ or sign a written informed consent.
PROCEDURE: Lung Surgery, RADIATION: Radiation therapy
Non-Small Cell Lung Cancer, Lung/Thoracic
UT Southwestern; Parkland Health & Hospital System
CAR-T Long Term Follow Up (LTFU) Study (PAVO)
Per Health Authorities guidelines for gene therapy medicinal products that utilize integrating vectors (e.g. lentiviral vectors), long term safety and efficacy follow up of treated patients is required. The purpose of this study is to monitor all patients exposed to CAR-T therapied for 15 years following their last CAR-T (e.g. CTL019) infusion to assess the risk of delayed adverse events (AEs), monitor for replication competent lentivirus (RCL) and assess long-term efficacy, including vector persistence.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Samuel John
ALL
0 Years to 100 Years old
PHASE3
NCT02445222
STU 032015-068
Inclusion Criteria:
* All patients who have received a CAR-T therapy and completed or discontinued early from a Novartis sponsored treatment protocol that utilized CAR-T cells or from any CAR-T trial sponsored by the University of Pennsylvania with which Novartis has a contractual agreement to co-develop the CAR technology.
* Patients who have provided informed consent for the long term follow up study prior to their study participation .
Exclusion Criteria:
* There are no specific exclusion criteria for this study. GENETIC: Previously treated CAR-T patients
Long Term Safety of Patients Receiving CAR-T in an Eligible Clinical Trial or Managed Access Program, Leukemia, Other
Children’s Health
A Phase II/III Trial of Nivolumab, Ipilimumab, and GM-CSF in Patients With Advanced Melanoma
This phase II/III trial studies the side effects of nivolumab and ipilimumab when given together with or without sargramostim and to see how well they work in treating patients with stage III-IV melanoma that cannot be removed by surgery (unresectable) and that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Colony-stimulating factors, such as sargramostim, may increase the production of white blood cells. It is not yet known whether nivolumab and ipilimumab are more effective with or without sargramostim in treating patients with melanoma.
studyfinder@utsouthwestern.edu
ALL
18 Years and over
PHASE2
NCT02339571
Inclusion Criteria:
* All patients must be \>= 18 years of age
* Eastern Cooperative Oncology Group (ECOG) performance status: 0 or 1
* Patients must have known BRAF mutational status of tumor; wild-type (WT) or mutated, prior to randomization
* Patients must not be pregnant or breast-feeding due to use of cytotoxic immunotherapy and risk of teratogenic side effects; all patients of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy; a patient of childbearing potential is anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patients must not conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of study registration and continuing (for patients of child bearing potential) for at least 5 months after the last dose of protocol treatment; patients of childbearing potential must also not donate eggs during this same time period
* Patients must have unresectable stage III or stage IV melanoma according to American Joint Committee on Cancer (AJCC) version (v)7; patients must have histological or cytological confirmation of melanoma that is metastatic or unresectable and clearly progressive
* Patients must have measurable disease per RECIST 1.1 criteria; all sites of disease must be evaluated within 4 weeks prior to randomization
* Patients may have had prior systemic therapy in the adjuvant setting (e.g. interferon, BRAF, or MEK agents). Patients may have had prior anti-CTLA-4 in the adjuvant setting, if at least one year from last dose of treatment has passed prior to beginning treatment. Patients may have had any prior anti-PD-1 or anti-PD-L1 agent in the adjuvant setting, if at least one year from last dose of treatment has passed prior to beginning treatment
* Patients may not have had any prior ipilimumab and/or anti-PD-1/PD-L1 agent in the metastatic setting
* Patients must have discontinued chemotherapy, immunotherapy or other investigational agents used in the adjuvant setting \>= 4 weeks prior to randomization and recovered from adverse events due to those agents; mitomycin and nitrosoureas must have been discontinued at least 6 weeks prior to entering the study; patients must have discontinued radiation therapy \>= 2 weeks prior to entering the study and recovered from any adverse events associated with treatment; prior surgery must be \>= 4 weeks from randomization and patients must be fully recovered from post-surgical complications
* Patients must not receive any other investigational agents while on study or within four weeks prior to randomization
* Patient must not have received any live vaccine within 30 days prior to randomization, while participating in the study, and for 4 weeks (28 days) after the last dose of protocol treatment; live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine; patients are permitted to receive inactivated vaccines and any non-live vaccines including those for the seasonal influenza and coronavirus disease 19 (COVID-19) (Note: intranasal influenza vaccines, such as Flu-Mist (registered trademark) are live attenuated vaccines and are not allowed); if possible, it is recommended to separate study drug administration from vaccine administration by about a week (primarily, in order to minimize an overlap of adverse events)
* Patients are ineligible if they have any currently active central nervous system (CNS) metastases; patients who have treated brain metastases (with either surgical resection or stereotactic radiosurgery) that have been stable on head magnetic resonance imaging (MRI) or contrast computed tomography (CT) scan for at least 4 weeks following treatment and within 4 weeks prior to randomization are eligible; patients must not have taken any steroids =\< 14 days prior to randomization for the purpose of managing their brain metastases; patients with only whole brain irradiation for treatment of CNS metastases will be ineligible
* Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast; patients with other malignancies are eligible if they have been continuously disease-free for \> 3 years prior to the time of randomization
* White blood count \>= 3,000/uL (obtained within 4 weeks prior to randomization)
* Absolute neutrophil count (ANC) \>= 1,500/uL (obtained within 4 weeks prior to randomization)
* Platelet count \>= 100,000/uL (obtained within 4 weeks prior to randomization)
* Hemoglobin \>= 9 g/dL (obtained within 4 weeks prior to randomization)
* Serum creatinine =\< 1.5 x upper limit of normal (ULN) or serum creatinine clearance (CrCl) \>= 40 ml/min (obtained within 4 weeks prior to randomization)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x ULN (=\< 5 x ULN for patients with documented liver metastases) (obtained within 4 weeks prior to randomization)
* Alkaline phosphatase =\< 2 x ULN (=\< 5 x ULN for patients with known liver involvement and =\< 7 x ULN for patients with known bone involvement) (obtained within 4 weeks prior to randomization)
* Total bilirubin =\< 1.5 x ULN except patients with normal direct bilirubin; those patients with known Gilbert's syndrome must have total bilirubin \< 3 x ULN (obtained within 4 weeks prior to randomization)
* Serum lactate dehydrogenase (LDH) =\< 10 X ULN (obtained within 4 weeks prior to randomization)
* Patients must not have any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), including but not limited to, ongoing or active infection requiring parenteral antibiotics on day 1, history of bleeding diathesis or need for concurrent anticoagulation (international normalized ratio \[INR\] =\< 1.5 and partial thromboplastin time \[PTT\] within 1.1 x ULN), or psychiatric illness/social situations that would limit compliance with study requirements, interfere with patient's safety, or obtaining informed consent
* Patients with human immunodeficiency virus (HIV) infection are ineligible; due to the mechanism of action of ipilimumab and GM-CSF, activity and side effects in an immune compromised patient are unknown
* Patients with evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are not eligible; patients with cleared HBV and HCV (0 viral load) infection will be allowed
* Patients must not have autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (e.g., prednisone, dexamethasone) or continuous use of topical steroid creams or ointments or ophthalmologic steroids; a history of occasional (but not continuous) use of steroid inhalers is allowed; replacement doses of steroids for patients with adrenal insufficiency are allowed; patients who discontinue use of these classes of medication for at least 2 weeks prior to randomization are eligible if, in the judgment of the treating physician investigator, the patient is not likely to require resumption of treatment with these classes of drugs during the study
* Exclusion from this study also includes patients with a history of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, Sjogren's syndrome, autoimmune vasculitis \[e.g., Wegener's granulomatosis\]); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis); other CNS autoimmune disease (e.g., multiple sclerosis)
* Patients with autoimmune hypothyroid disease or type I diabetes on replacement treatment are eligible
* Patients must not have a history of inflammatory bowel disease or diverticulitis (history of diverticulosis is allowed)
* Patients must not have other significant medical, surgical, or psychiatric conditions or require any medication or treatment that in the opinion of the investigator may interfere with compliance, make the administration of the study drugs hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea; patients must not have an active infection requiring current treatment with parenteral antibiotics PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, BIOLOGICAL: Ipilimumab, PROCEDURE: Magnetic Resonance Elastography, PROCEDURE: Multigated Acquisition Scan, BIOLOGICAL: Nivolumab, BIOLOGICAL: Sargramostim
Stage III Cutaneous Melanoma AJCC v7, Stage IV Cutaneous Melanoma AJCC v6 and v7
Adjuvant Curcumin to Assess Recurrence Free Survival in Patients Who Have Had a Radical Prostatectomy
This is a prospective study to determine if the adjuvant use of Curcumin improves recurrence-free survival.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yair Lotan
MALE
30 Years to 80 Years old
PHASE3
NCT02064673
STU 042013-080
Inclusion Criteria:
* Status post radical prostatectomy for histologically confirmed adenocarcinoma of the prostate
* pathologically confirmed T1-T3 disease
* no sign of lymph node or metastatic disease
* pT1-pT3pNxMx patients in whom standard NCCN or AUA guidelines would suggest are at low risk for pelvic lymph node or metastatic disease and who would not require confirmatory imaging for metastatic disease. This includes patients with Gleason 6 or 7(T2 disease) and PSA less than 20.
* Eastern Cooperative Oncology Group(ECOG) status 0-2
* adequate renal and liver function as well as bone marrow reserve (measured serum creatinine \<2mg/dl, bilirubin ≤ 1.5 mg/dl, ANC ≥ 1.5 x 10 (3) uL, platelets ≥ 50 x K/uLL, and hemoglobin ≥ 10 g/dL)
* 30-80 y/o at time of diagnosis with a life expectancy of \>= 3 yrs
* focally positive surgical margins are permitted
* no plan to receive adjuvant hormone or radiation therapy
* PSA at the time of enrollment must be undetectable
* life expectancy of 3 years
Exclusion Criteria:
* must not have exceeded 3 months from time of surgery to enrollment into study
* T3b or T4 or node positive disease
* macroscopic residual disease after surgery
* hormone therapy before surgery
* history of gallbladder problems or gallstones, or biliary obstruction, unless patient had cholecystectomy
* radiation therapy as primary treatment after surgery
* INR value greater than 1.5
* AST/ALT are equal or greater than 2 times the upper limit of normal
* antiplatelet or anticoagulant agents- patients taking 81mg of Aspirin will be allowed with close observation
* history of gastric or duodenal ulcers or untreated hyperacidity syndromes
* patients who are currently taking curcumin and are unwilling to stop or plan to take curcumin during the study DRUG: Curcumin, DRUG: placebo
Prostate Cancer, Prostate
prostate cancer, radical prostatectomy
UT Southwestern; Parkland Health & Hospital System
Metabolic Biomarkers in Thoracic Cancers
The purpose of this research study is to develop a method of using magnetic resonance imaging (MRI) to evaluate lung tumors and other thoracic malignancies. An MRI is a scanning device that uses magnets to make images (pictures) of the body. This study is being done to determine what series of reactions (metabolic pathways) pulmonary nodules use as they burn sugar as fuel for growth. The manner in which the tumor burns (metabolizes) sugar for fuel is being investigated by using a natural, slightly modified, sugar solution (13C-glucose) and studying a small sample of the tumor once it is removed at the time of surgery.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kemp Kernstine
ALL
18 Years and over
NA
NCT02095808
STU 052012-065
Inclusion Criteria:
• Patients must have known or probable malignant lesions requiring surgical biopsy or excision.
• Subjects of all races and ethnic origins over 18 years of age.
Exclusion Criteria:
• Not a surgical candidate.
• Poorly controlled diabetes.
PROCEDURE: Imaging Biomarkers
Lung Cancer, Lung/Thoracic
UT Southwestern
Testing Docetaxel-Cetuximab or the Addition of an Immunotherapy Drug, Atezolizumab, to the Usual Chemotherapy and Radiation Therapy in High-Risk Head and Neck Cancer
This phase II/III trial studies how well radiation therapy works when given together with cisplatin, docetaxel, cetuximab, and/or atezolizumab after surgery in treating patients with high-risk stage III-IV head and neck cancer the begins in the thin, flat cells (squamous cell). Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cetuximab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The purpose of this study is to compare the usual treatment (radiation therapy with cisplatin chemotherapy) to using radiation therapy with docetaxel and cetuximab chemotherapy, and using the usual treatment plus an immunotherapy drug, atezolizumab.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Sher
ALL
18 Years and over
PHASE2
NCT01810913
STU 022013-055
Inclusion Criteria:
* PHASE II INCLUSION CRITERIA (COMPLETE AS OF 20-MAR-2020)
* Pathologically (histologically or cytologically) proven diagnosis of head and neck squamous cell carcinoma (HNSCC) involving the oral cavity (excluding lips), oropharynx (p16 negative), larynx, or hypopharynx
* Patients must have undergone gross total surgical resection of high-risk oral cavity, oropharynx (p16 negative), larynx, or hypopharynx within 63 days prior to registration; Note: patients may have biopsy under general anesthesia in an operating room followed by definitive ablative cancer surgery representing gross total resection; the gross total resection has to be done within 63 days prior to registration; if, however, patients have ablative resection but shortly recur or are determined to have persisting disease requiring re-resection to achieve gross total resection, then the patient is not eligible
* Patients must have at least 1 of the following high-risk pathologic features: extracapsular nodal extension or invasive cancer at the primary tumor resection margin (tumor on ink)
* Pathologic stage III or IV HNSCC, including no distant metastases, based upon the following minimum diagnostic workup:
* General history and physical examination by a radiation oncologist and/or medical oncologist within 84 days prior to registration;
* Examination by an ear nose throat (ENT) or head \& neck surgeon prior to surgery; a laryngopharyngoscopy (mirror and/or fiber optic and/or direct procedure), if appropriate, is recommended but not required; intra-operative examination is acceptable documentation
* Pre-operative (op) Imaging of the head and neck: A neck computed tomography (CT) (with contrast) or CT/positron emission tomography (PET) (with contrast) and/or an magnetic resonance imaging (MRI) of the neck (T1 with gadolinium and T2) within 84 days prior to surgery; Note: this imaging data (diagnostic pre-operative scan showing gross disease) is to be submitted in Digital Imaging and Communications in Medicine (DICOM) format via TRIAD; the report is to be uploaded into Rave
* Chest CT scan (with or without contrast) or CT/PET that includes the chest (with or without contrast) either within 84 days prior to surgery or within 120 days prior to registration; Note: if the CT/PET with or without contrast is done within 84 days prior to surgery, it fulfills the chest imaging requirement
* Zubrod performance status of 0-1 within 14 days prior to registration
* Age \>= 18
* Absolute granulocyte count (AGC) \>= 1,500 cells/mm\^3 (obtained within 14 days prior to registration on study)
* Platelets \>= 100,000 cells/mm\^3 (obtained within 14 days prior to registration on study)
* Hemoglobin \>= 8.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 8.0 g/dl is acceptable)
* Total bilirubin \< 2 x institutional upper limit of normal (ULN) within 14 days prior to registration
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \< 3 x institutional ULN within 14 days prior to registration
* Serum creatinine institutional ULN within 14 days prior to registration or; creatinine clearance (CC) \>= 50 ml/min within 14 days prior to registration determined by 24-hour collection or estimated by Cockcroft-Gault formula
* Negative urine or serum pregnancy test within 14 days prior to registration for women of childbearing potential
* The following assessments are required within 14 days prior to registration: sodium (Na), potassium (K), chloride (Cl), glucose, calcium (Ca), magnesium (Mg), and albumin; Note: patients with an initial magnesium \< 0.5 mmol/L (1.2 mg/dl) may receive corrective magnesium supplementation but should continue to receive either prophylactic weekly infusion of magnesium and/or oral magnesium supplementation (e.g., magnesium oxide) at the investigator's discretion
* Patients with feeding tubes are eligible for the study
* Women of childbearing potential and male participants who are sexually active must agree to use a medically effective means of birth control
* Patient must provide study specific informed consent prior to study entry, including consent for mandatory tissue submission for epidermal growth factor receptor (EGFR) analysis and for oropharyngeal cancer patients, human papilloma virus (HPV) analysis
* PHASE III: Pathologically (histologically or cytologically) proven diagnosis of head and neck squamous cell carcinoma (HNSCC) involving the oral cavity (excluding lips), oropharynx (p16 negative), larynx, or hypopharynx
* PHASE III: Patients with oropharyngeal cancer must have p16-negative based on central review prior to Step 2 registration. All patients with oropharyngeal primary must consent for mandatory tissue submission for central p16 confirmation
* PHASE III: Patients must have undergone gross total surgical resection of high-risk oral cavity, oropharynx (p16 negative), larynx, or hypopharynx within 63 days prior to registration
* Note: Patients may have biopsy under general anesthesia in an operating room followed by definitive ablative cancer surgery representing gross total resection. The gross total resection has to be done within 63 days prior to registration. If, however, patients have ablative resection but shortly recur or are determined to have persisting disease requiring re-resection to achieve gross total resection, then the patient is not eligible
* PHASE III: Patients must have at least 1 of the following high-risk pathologic features: extracapsular nodal extension or invasive cancer at the primary tumor resection margin (tumor on ink or tumor in a final separately submitted margin)
* PHASE III: Pathologic stage III or IV HNSCC (American Joint Committee on Cancer \[AJCC\] 7th edition), including no distant metastases, based upon the following minimum diagnostic workup:
* General history and physical examination by a radiation oncologist or medical oncologist within 84 days prior to registration;
* Examination by an ENT or head \& neck surgeon prior to surgery; a laryngopharyngoscopy (mirror or fiberoptic or direct procedure), if appropriate, is recommended but not required. Intra-operative examination is acceptable documentation.
* Pre-op Imaging of the head and neck: A neck CT (with contrast and of diagnostic quality) or PET/CT (with contrast and of diagnostic quality) and/or an MRI of the neck of diagnostic quality (T1 with gadolinium and T2) within 84 days prior to surgery; Note: this imaging data (diagnostic pre-operative scan showing gross disease) is to be submitted in DICOM format via TRIAD. The report is to be uploaded into Rave.
* Chest CT scan (with or without contrast) or PET/CT that includes the chest (with or without contrast) either within 84 days prior to surgery or within 120 days prior to registration; Note: If the PET/CT with or without contrast is done within 84 days prior to surgery, it fulfills the chest imaging requirement
* PHASE III: Zubrod performance status of 0-1 within 14 days prior to registration
* PHASE III: Age \>= 18
* PHASE III: Leukocytes \>= 2,500 cells/mm\^3 (obtained within 14 days prior to registration on study)
* PHASE III: Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3 (obtained within 14 days prior to registration on study)
* PHASE III: Platelets \>= 100,000 cells/mm\^3 (obtained within 14 days prior to registration on study)
* PHASE III: Hemoglobin \>= 8.0 g/dL (Note: The use of transfusion or other intervention to achieve Hgb \>= 8.0 g/dL is acceptable) (obtained within 14 days prior to registration on study)
* PHASE III: Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level =\< 3 x institutional ULN may be enrolled) (within 14 days prior to registration)
* PHASE III: AST or ALT =\< 3 x institutional ULN (within 14 days prior to registration)
* PHASE III: Alkaline phosphatase =\< 2.5 x institutional ULN (within 14 days prior to registration)
* PHASE III: Creatinine clearance (CrCl) \>= 50 mL/min within 14 days prior to registration determined by 24-hour collection or estimated by Cockcroft-Gault formula
* PHASE III: Patients with feeding tubes are eligible for the study
* PHASE III: Negative urine or serum pregnancy test within 14 days prior to registration for women of childbearing potential
* PHASE III: All patients must provide study specific informed consent prior to study entry
* PHASE III: Patients positive for human immunodeficiency virus (HIV) are allowed on study, but HIV-positive patients must have:
* A stable regimen of highly active anti-retroviral therapy (HAART);
* No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections;
* A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard polymerase chain reaction (PCR)-based tests
Exclusion Criteria:
* PHASE II EXCLUSION CRITERIA (COMPLETE AS OF 20-MAR-2020)
* Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years); noninvasive cancers (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible) are permitted even if diagnosed and treated \< 3 years ago
* Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 resected differentiated thyroid carcinoma, who are eligible
* Prior systemic chemotherapy or anti-epidermal growth factor (EGF) therapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* Severe, active co-morbidity, defined as follows:
* Unstable angina and/or congestive heart failure requiring hospitalization within 6 months prior to registration
* Transmural myocardial infarction within 6 months prior to registration
* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
* Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires oxygen therapy or is thought to require oxygen therapy within 1 year prior to registration
* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol
* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease and Control and Prevention (CDC) definition; note: human immunodeficiency virus (HIV) testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive; protocol-specific requirements may also exclude immuno-compromised patients.
* Grade 3-4 electrolyte abnormalities (Common Terminology Criteria for Adverse Events \[CTCAE\], version \[v.\] 4):
* Serum calcium (ionized or adjusted for albumin) \< 7 mg/dl (1.75 mmol/L) or \> 12.5 mg/dl (\> 3.1 mmol/L) despite intervention to normalize levels
* Glucose \< 40 mg/dl (\< 2.2 mmol/L) or \> 250 mg/dl (\> 14 mmol/L)
* Magnesium \< 0.9 mg/dl (\< 0.4 mmol/L) or \> 3 mg/dl (\> 1.23 mmol/L) despite intervention to normalize levels
* Potassium \< 3.0 mmol/L or \> 6 mmol/L despite intervention to normalize levels
* Sodium \< 130 mmol/L or \> 155 mmol/L despite intervention to normalize levels
* Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
* Prior allergic reaction to cetuximab
* PHASE III: Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) with the following exceptions: T1-2, N0, M0 resected differentiated thyroid carcinoma; Note that noninvasive cancers (For example, carcinoma in situ of the breast, oral cavity, or cervix) are permitted even if diagnosed and treated \< 3 years ago
* PHASE III: Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 resected differentiated thyroid carcinoma, who are eligible
* PHASE III: Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted therapy (such as anti-EGF therapy), or immune therapy for the study cancer; note that prior chemotherapy for a different cancer is allowable, however, a prior anti-PD-1, anti-PD-L1, or anti-PD-L2 agent is not permitted
* PHASE III: Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* PHASE III: Severe, active co-morbidity, defined as follows:
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification; to be eligible for this trial, patients should be class 2B or better within 6 months prior to registration
* Transmural myocardial infarction within 6 months prior to registration;
* Severe infections within 4 weeks prior to registration including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia;
* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; Note: Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible.
* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration;
* History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in a prior radiation field (fibrosis) is permitted, provided that field does not overlap with the planned radiation field for the study cancer;
* Patients with active tuberculosis (TB) are excluded;
* Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease;
* Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen \[HBsAg\] test and a positive anti-HBc \[antibody to hepatitis B core antigen\] antibody test) are eligible.
* Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
* History of allogeneic bone marrow transplantation or solid organ transplantation.
* A diagnosis of immunodeficiency:
* Acquired immune deficiency syndrome (AIDS) based upon current CDC definition; note: HIV testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
* Is receiving treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 2 weeks prior to registration.
* Note: Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled.
* Note: The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
* History or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
* Patients with a history of autoimmune hypothyroidism who are asymptomatic and/or are on a stable dose of thyroid replacement hormone are eligible.
* Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible.
* Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
* Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
* Rash must cover less than 10% of body surface area (BSA)
* Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%)
* No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation \[PUVA\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
* PHASE III: Grade 3-4 electrolyte abnormalities (CTCAE, v. 4) within 14 days prior to registration:
* Serum calcium (ionized or adjusted for albumin) \< 7 mg/dL (1.75 mmol/L) or \> 12.5 mg/dL (\> 3.1 mmol/L) despite intervention to normalize levels;
* Glucose \< 40 mg/dL (\< 2.2 mmol/L) or \> 250 mg/dL (\> 14 mmol/L);
* Magnesium \< 0.9 mg/dL (\< 0.4 mmol/L) or \> 3 mg/dL (\> 1.23 mmol/L) despite intervention to normalize levels;
* Potassium \< 3.0 mmol/L or \> 6 mmol/L despite intervention to normalize levels;
* Sodium \< 130 mmol/L or \> 155 mmol/L despite intervention to normalize levels.
* PHASE III: Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception for up to 5 months from last study treatment; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic. Women who are breastfeeding and unwilling to discontinue are also excluded
* PHASE III: History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
* PHASE III: Patients taking bisphosphonate therapy for symptomatic hypercalcemia. Use of bisphosphonate therapy for other non-oncologic reasons (e.g., osteoporosis) is allowed
* PHASE III: Patients requiring treatment with a RANKL inhibitor (e.g. denosumab) for non-oncologic reasons who cannot discontinue it before registration
* PHASE III: Patients with known distant metastatic disease are excluded
* PHASE III: Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
* PHASE III: Major surgical procedure within 28 days prior to registration or anticipation of need for a major surgical procedure during the course of the study
* PHASE III: Administration of a live, attenuated vaccine within 4 weeks prior to registration or anticipation that such a live, attenuated vaccine will be required during the study and for patients receiving atezolizumab, up to 5 months after the last dose of atezolizumab.
* Influenza vaccination should be given during influenza season only (approximately October to DRUG: Atezolizumab, PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, BIOLOGICAL: Cetuximab, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Docetaxel, RADIATION: Intensity-Modulated Radiation Therapy, PROCEDURE: Magnetic Resonance Imaging, OTHER: Survey Administration
Oropharyngeal p16INK4a-Negative Squamous Cell Carcinoma, Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7, Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7, Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7, Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7, Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7, Stage IV Laryngeal Squamous Cell Carcinoma AJCC v7, Stage IV Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7, Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7
UT Southwestern; Parkland Health & Hospital System