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Search Results Within Category "Digestive Systems & Liver Disease"
71 Study Matches
Study of XL092 in Combination With Immuno-Oncology Agents in Subjects With Solid Tumors (STELLAR-002)
This is a multicenter Phase 1b, open label, dose-escalation and cohort-expansion study, evaluating the safety, tolerability, PK, preliminary antitumor activity, and effect of biomarkers of XL092 administered alone, and in combination with nivolumab (doublet), nivolumab + ipilimumab (triplet) and nivolumab + relatlimab (triplet) in subjects with advanced solid tumors. In the Expansion Stage, the safety and efficacy of XL092 as monotherapy and in combination therapy will be further evaluated in tumor-specific Expansion Cohorts.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Hans Hammers
169573
All
18 Years and over
Phase 1
NCT05176483
STU-2022-0177
Inclusion Criteria:
• Cytologically or histologically confirmed solid tumor that is unresectable, locally advanced or metastatic.
• Dose-Escalation Cohorts: Subjects with a solid tumor that is unresectable or metastatic and for which life-prolonging therapies do not exist or available therapies are intolerable or no longer effective.
• Expansion Cohort 1 (ccRCC): Subjects with unresectable advanced or metastatic RCC with a clear cell component who have not received prior systemic therapy.
• Note: Prior non-VEGF targeted adjuvant or neoadjuvant is allowed if disease recurrence occurred 6 months after the last dose.
• Expansion Cohort 2 (ccRCC): Subjects with unresectable advanced or metastatic RCC with a clear cell component.
• Must have radiographically progressed after a combination therapy consisting of a PD-1/PD-L1 targeting mAb with a VEGFR-TKI or a PD-1 targeting mAb with a CTLA-4 mAb as the preceding line of therapy.
• Must have received no more than one prior systemic anticancer therapy for unresectable advanced or metastatic renal cell carcinoma.
• Expansion Cohort 3 (mCRPC): Men with metastatic adenocarcinoma of the prostate.
• Must have progressed during or after one NHT given for castration-sensitive locally advanced (T3 or T4) or metastatic castration-sensitive prostate cancer (CSPC), M0 CRPC, or mCRPC.
• Expansion Cohort 4 (UC, ICI-naive): Subjects with histologically confirmed unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra).
• Must have progressed during or after prior first-line platinum-based combination therapy, including subjects who received prior neoadjuvant or adjuvant platinum-containing therapy with disease recurrence < 12 months from the end of last therapy.
• Must have received no more than 1 prior line of systemic anticancer therapy for unresectable, locally advanced or metastatic disease.
• Expansion Cohort 5 (UC, ICI-experienced): Subjects with histologically confirmed unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra).
• Must have progressed during or after prior PD-1/PD-L1 targeting ICI therapy given as monotherapy, combination therapy, maintenance therapy or adjuvant therapy.
• Must have received no more than 2 prior lines of systemic anticancer therapy for unresectable advanced or metastatic disease.
• Expansion Cohort 6 (nccRCC): Subjects with unresectable advanced or metastatic nccRCC of the following subtypes: Papillary RCC (any type), unclassified RCC, and translocation-associated. Among the eligible histologic subtypes, sarcomatoid features are allowed.
• No prior systemic anticancer therapy is allowed except adjuvant or neoadjuvant therapy if disease recurrence occurred at least 6 months after the last dose.
• Expansion Cohort 7 (HCC): Subjects with inoperable locally advanced, recurrent, or metastatic HCC that is not amenable to curative treatment or locoregional therapy.
• Expansion Cohort 8 (NSCLC): Subjects with Stage IV non-squamous NSCLC with positive PD-L1 expression (tumor proportion score [TPS] 1-49%) and without prior systemic anticancer therapy for metastatic disease.
• Expansion Cohort 9 (NSCLC): Subjects with Stage IV non-squamous NSCLC who have radiologically progressed following treatment with one prior immune checkpoint inhibitor (anti-PD-1 or anti-PD-L1) for metastatic disease.
• Expansion Cohort 10 (CRC): Subjects with histologically confirmed unresectable, locally advanced, or metastatic adenocarcinoma of the colon or rectum.
• Expansion Cohort 11 (HNSCC): Subject with inoperable, refractory, recurrent or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx. PD-L1 combined positive score (CPS) ≥1.
• For all Expansion Cohorts except Cohort 3: Measurable disease per RECIST 1.1 as determined by the Investigator.
• For expansion cohorts only: Archival tumor tissue material, if available, or fresh tumor tissue if it can be safely obtained.
• Recovery to baseline or ≤ Grade 1 CTCAE v5 from AE(s) related to any prior treatments unless AE(s) are deemed clinically nonsignificant by the Investigator and/or stable on supportive therapy.
• Karnofsky Performance Status (KPS) ≥ 70%.
• Adequate organ and marrow function.
• Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception.
• Female subjects of childbearing potential must not be pregnant at screening.
Exclusion Criteria:
• For all Dose-Escalation cohorts: Prior treatment with XL092. For all Expansion Cohorts: Prior treatment with XL092, nivolumab, ipilimumab or relatlimab with the following exceptions: Prior PD-1/PD-L1, LAG-3 and CTLA-4 targeting therapy for locally advanced or metastatic disease is allowed for Cohort 2 (ccRCC), Cohort 5 (UC), Cohort 9 (NSCLC).
• For all Dose-Escalation Cohorts and Expansion Cohort 2 (ccRCC), 3 (mCRPC), Cohort 5 (UC), Cohort 9 (NSCLC) and Cohort 10 (CRC): Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
• For Cohort 3 (mCRPC): Receipt of abiraterone within 1 week; cyproterone within 10 days; or receipt of flutamide, nilutamide, bicalutamide, enzalutamide, or other androgen receptor inhibitors within 2 weeks before first dose of study treatment.
• For all Dose-Escalation Cohorts and Expansion Cohort 2 (ccRCC), Cohort 3 (mCRPC), Cohort 5 (UC), Cohort 9 (NSCLC) and Cohort 10 (CRC): Receipt of any type of anticancer antibody or systemic chemotherapy within 4 weeks before first dose of study treatment.
• Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first dose of study treatment.
• Prior external radiation therapy for bone metastasis within 2 weeks, for other tumor sites within 4 weeks, and prior radium-223 therapy within 6 weeks before first dose of study treatment, unless otherwise specified.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy (including radiosurgery) or surgically removed and stable for at least 4 weeks before first dose of study treatment.
• Concomitant anticoagulation with oral anticoagulants and platelet inhibitors.
• Administration of a live, attenuated vaccine within 30 days prior to enrollment.
• Uncontrolled, significant intercurrent or recent illness.
• Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per electrocardiogram (ECG) within 14 days before first dose of study treatment.
• Subjects with inadequately treated adrenal insufficiency.
• Pregnant or lactating females.
• Any other active malignancy within two years before first dose of study treatment, except for locally curable cancers that have been apparently cured such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
• For Cohort 2 (ccRCC, 2L): Receipt of a prior triplet therapy including a VEGFR-TKI, a PD1 targeting mAb, and a CTLA-4 mAb.
• For Cohort 3 (mCRPC): Receipt of a taxane-based chemotherapy for mCRPC.
• For Cohort 4 (UC, ICI-naïve): Subjects who have had recurrence within the 6 months of completing adjuvant anti-PD-(L)1 treatment.
• For Cohort 6 (nccRCC, 1L): Subjects with chromophobe, renal medullary carcinoma, or pure collecting duct nccRCC.
• For Cohort 7 (HCC):
• Documented hepatic encephalopathy (HE) within 6 months before randomization (see Section 6.5.2 for a case definition of HE).
• Clinically meaningful ascites (ie, ascites requiring paracentesis or escalation in diuretics) within 6 months before randomization.
• Subjects who have received any local anticancer therapy including surgery, PEI, RFA, MWA, transarterial chemoembolization (TACE), or transarterial radioembolization (TARE) within 28 days prior to randomization.
• Subjects with known fibrolamellar carcinoma, sarcomatoid HCC, or mixed hepatocellular cholangiocarcinoma
• For Cohort 10 (CRC, 2L+): Receipt of prior therapy with regorafenib and/or TAS-102.
• For Cohort 11 (HNSCC): Primary tumor site of the nasopharyngeal area.
• For Cohorts 1 (ccRCC, 1L), 2 (ccRCC, 2L), 4, 5 (UC), 7 (HCC), 8 (NSCLC 1L PD-L1 low), 9 (NSCLC, 2L+), 10 (CRC, MSS, 2L+), and 11 (HNSCC):
• Troponin T (TnT) or I (TnI) > 2 × institutional ULN. Note: Additional Inclusion and Exclusion criteria may apply.
Drug: XL092, Drug: Nivolumab, Drug: Ipilimumab, Drug: Nivolumab, Drug: Nivolumab, Drug: Nivolumab + Relatlimab
Non-Small Cell Lung Cancer, Hepatocellular Carcinoma, Colorectal Cancer, Renal Cell Carcinoma, Head and Neck Squamous Cell Carcinoma, Urothelial Carcinoma, Solid Tumor, Kidney, Prostate, Urinary Bladder, Metastatic Castration-resistant Prostate Cancer
UT Southwestern
Tempus Priority Study: A Pan-tumor Observational Study
Observational study that will be collecting clinical and molecular health information from cancer patients who have received comprehensive genomic profiling and meet the specific eligibility criteria outlined for each cohort with the goal of conducting research to advance cancer care and create a dataset that furthers cancer research.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Solomon Woldu
154531
ALL
Not specified
NCT05179824
STU-2020-0992
Inclusion Criteria:
• Solid or hematologic malignancy.
• Willing and able to provide informed consent where required.
• Has received or will receive genomic profiling.
Exclusion Criteria:
• Individuals without the capacity to consent.
• Prisoners at the time of enrollment.
OTHER: Observation
Lung Cancer, Prostate Cancer, Leukemia, Lymphoma, Breast Cancer, Pancreatic Cancer, Brain Cancer, Bladder Cancer, Ovarian Cancer, Fallopian Tube Cancer, Cancer of Head and Neck, Cancer of Gastrointestinal Tract, Peritoneal Cancer, Cancer of Liver, Cancer of Colon, Cancer of Stomach, Cancer of Rectum, Cancer of Esophagus, Cancer of Skin, Cancer of Cervix, Cancer of Kidney, Cancer of Larynx, Cancer of Endometrium, Cancer of the Bile Duct, Cancer of Vulva, Cancer of Bone and Connective Tissue, Spinal Cord Cancer
Cancer, Oncology, Observational, Genomic Profiling, Precision Medicine
UT Southwestern
Colon Adjuvant Chemotherapy Based on Evaluation of Residual Disease (CIRCULATE-US)
This Phase II/III trial will evaluate the what kind of chemotherapy to recommend to patients based on the presence or absences of circulating tumor DNA (ctDNA) after surgery for colon cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Nilesh Verma
219135
ALL
18 Years and over
PHASE2
NCT05174169
STU-2023-0699
Inclusion Criteria:
The patient must have an ECOG performance status of 0 or 1.
Patients must have histologically/pathologically confirmed colon adenocarcinoma (T1-3, N1/N1c) with R0 resection accordingly to AJCC 8th edition criteria. NOTE: Patients with pathologic stages II or IIIC colon adenocarcinoma with R0 resection who have a commercially obtained Signatera™ ctDNA+ve assay result post-operatively meeting all timelines and eligibility requirements otherwise, are eligible for enrollment and inclusion in Cohort B.
No radiographic evidence of overt metastatic disease within 28 days prior to study entry (CT with IV contrast or MRI imaging is acceptable and must include chest, abdomen, and pelvis).
The distal extent of the tumor must be greater than or equal to 12 cm from the anal verge on colonoscopy or above the peritoneal reflection as documented during surgery or on pathology specimen (i.e., excluding rectal adenocarcinomas warranting treatment with chemoradiation).
The patient must have had an en bloc complete gross resection of tumor (curative resection). Patients who have had a two-stage surgical procedure, to first provide a decompressive colostomy and then in a later procedure to have the definitive surgical resection, are eligible.
The resected tumor specimen and a blood specimen from patients with Stage IIIA or Stage IIIB colon cancer must have central testing for ctDNA using the Signatera™ assay by Natera.
NOTE: Patients with stage IIIA or IIIB colon cancer who otherwise meet eligibility criteria and have had ctDNA status checked with the Signatera™ assay as routine care outside of the study, are allowed to be enrolled, and will be retested and placed in either Cohort A or Cohort B depending on the central ctDNA testing result.
NOTE: Patients with stage II or IIIC colon cancer who otherwise meet eligibility criteria and have had ctDNA status checked with the Signatera™ assay as routine care outside of the study AND have a ctDNA+ve result, are allowed to be enrolled. Patients will have central ctDNA testing, confirmed to be ctDNA+ve, and placed in Cohort B.
Tumor must be documented as microsatellite stable or have intact mismatch repair proteins through CLIA-approved laboratory testing. Patients whose tumors are MSI-H or dMMR are excluded.
The treating investigator must deem the patient a candidate for all potential agents used in this trial (5FU, LV, oxaliplatin and irinotecan).
The interval between surgery (post-operative Day 7) and study entry must be no more than 60 days.
Availability and provision of adequate surgical tumor tissue for molecular diagnostics and confirmatory profiling.
Adequate hematologic function within 28 days before study entry defined as follows:
* Absolute neutrophil count (ANC) must be greater than or equal to 1500/mm3;
* Platelet count must be greater than or equal to 100,000/mm3; and
* Hemoglobin must be greater than or equal to 9 g/dL.
Adequate hepatic function within 28 days before study entry defined as follows:
* total bilirubin must be less than or equal to ULN (upper limit of normal) for the lab and
* alkaline phosphatase must be less than 2.5 x ULN for the lab; and
* AST and ALT must be less than 2.5 x ULN for the lab.
Adequate renal function within 28 days before study entry defined as serum creatinine less than or equal to 1.5 x ULN for the lab or measured or calculated creatinine clearance greater than or equal to 50 mL/min using the Cockroft-Gault formula for patients with creatinine levels greater than 1.5 x ULN for the lab.
For Women Creatinine Clearance (mL/min) = (140 - age) x weight (kg) x 0.85 72 x serum creatinine (mg/dL) For Men Creatinine Clearance (mL/min) = (140 - age) x weight (kg) 72 x serum creatinine (mg/dL)
HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
Pregnancy test (urine or serum according to institutional standard) done within 14 days before study entry must be negative (for women of childbearing potential only).
Patients receiving a coumarin-derivative anticoagulant must agree to weekly monitoring of INR if they are randomized to Arm 1 or Arm 3 and receive capecitabine.
Eligibility Criteria for Cohort A Arm-2 patients on Second Randomization
Patient must have developed a ctDNA +ve assay during serial monitoring.
Patient's willingness to be re-randomized affirmed.
The patient must continue to have an ECOG performance status of 0 or 1.
No radiographic evidence of overt metastatic disease.
Pregnancy test (urine or serum according to institutional standard) done within 14 days before study entry must be negative (for women of childbearing potential only).
Adequate hematologic function within 28 days before randomization defined as follows:
* Absolute neutrophil count (ANC) must be greater than or equal to 1500/mm3;
* Platelet count must be greater than or equal to 100,000/mm3; and
* Hemoglobin must be greater than or equal to 9 g/dL.
Adequate hepatic function within 28 days before randomization defined as follows:
* total bilirubin must be less than or equal to ULN (upper limit of normal) for the lab and
* alkaline phosphatase must be less than 2.5 x ULN for the lab; and
* AST and ALT must be less than 2.5 x ULN for the lab.
Adequate renal function within 28 days before randomization defined as serum creatinine less than or equal to 1.5 x ULN for the lab or measured or calculated creatinine clearance greater than or equal to 50 mL/min using the Cockroft-Gault formula for patients with creatinine levels greater than 1.5 x ULN for the lab.
For Women Creatinine Clearance (mL/min) = (140 - age) x weight (kg) x 0.85 72 x serum creatinine (mg/dL) For Men Creatinine Clearance (mL/min) = (140 - age) x weight (kg) 72 x serum creatinine (mg/dL)
Exclusion Criteria:
Colon cancer histology other than adenocarcinoma (i.e., neuroendocrine carcinoma, sarcoma, lymphoma, squamous cell carcinoma, etc.).
Pathologic, clinical, or radiologic overt evidence of metastatic disease. This includes isolated, distant, or non-contiguous intra-abdominal metastases, even if resected.
Tumor-related bowel perforation.
History of prior invasive colon malignancy, regardless of disease-free interval.
History of bone marrow or solid organ transplantation (regardless of current immunosuppressive therapy needs). Bone grafts, skin grafts, corneal transplants and organ/tissue donation are not exclusionary.
Any prior systemic chemotherapy, targeted therapy, or immunotherapy; or radiation therapy administered as treatment for colorectal cancer (e.g., primary colon adenocarcinomas for which treatment with neoadjuvant chemotherapy and/or radiation is warranted are not permitted).
Other invasive malignancy within 5 years before study entry. Exceptions are colonic polyps, non-melanoma skin cancer or any carcinoma-in-situ.
Synchronous primary rectal and/ or colon cancers.
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.
Sensory or motor neuropathy greater than or equal to grade 2, according to CTCAE v5.0.
Blood transfusion within two weeks before collection of blood for central ctDNA testing.
Active seizure disorder uncontrolled by medication.
Active or chronic infection requiring systemic therapy.
Known homozygous DPD (dihydropyrimidine dehydrogenase) deficiency.
Patients known to have Gilbert's Syndrome or homozygosity for UGT1A1\*28 polymorphism.
Pregnancy or lactation at the time of study entry.
Co-morbid illnesses or other concurrent disease that would make the patient inappropriate for entry into this study (i.e., unable to tolerate 6 months of combination chemotherapy or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens or prevent required follow-up).
Ineligibility Criteria for Cohort A Arm-2 patients on Second Randomization
Pregnancy or lactation at the time of randomization.
No longer a candidate for systemic chemotherapy (FOLFOX, CAPOX, and mFOLFIRINOX) in the opinion of the treating investigator. DEVICE: Signatera test, DRUG: mFOLFOX6 3-6 month, DRUG: CAPOX 3 month, DRUG: mFOLFIRINOX, DRUG: mFOLFOX6 6 month, DRUG: CAPOX 6 month
Stage III Colon Cancer
ctDNA positive, ctDNA negative, Adjuvant Chemotherapy, Natera, Signatera, mFOLFOX6, Stage III, CAPOX, mFOLFIRINOX, Oxaliplatin, 5-Fluorouracil (5-FU), Capecitabine, Leucovorin, Irinotecan, Stage II
UT Southwestern; Parkland Health & Hospital System
Five or Ten Year Colonoscopy for 1-2 Non-Advanced Adenomatous Polyps (FORTE)
This trial examines colorectal cancer incidence in participants with 1 to 2 non-advanced adenomas randomized to surveillance colonoscopy at 10 years compared to participants randomized to surveillance colonoscopy at 5 and 10 years.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Luke Engelking
35166
All
50 Years to 70 Years old
N/A
NCT05080673
STU-2023-0888
Inclusion Criteria:
• • The participant must have signed and dated an IRB-approved consent form that conforms to federal and institutional guidelines.
• Participants with a first-time diagnosis of 1-2 non-advanced tubular adenomas (less than 10 mm without tubulovillous or villous changes or high grade or severe dysplasia) from the qualifying colonoscopy within 4 years prior to randomization.
• Sessile serrated polyps/adenomas, as long as they do not meet the criteria for advanced adenomas, will be considered as non-advanced adenomas.
• Qualifying colonoscopy must be a complete colonoscopy with visualization of the cecum and with adequate cleansing within 4 years prior to randomization.
• Complete excision of all observed polyps in qualifying colonoscopy
• Participants must be able to read or understand English or Spanish.
Exclusion Criteria:
• • Prior history of colorectal cancer or colorectal adenomas including sessile serrated polyps/adenomas excluding those found on the qualifying colonoscopy.
• Prior history of a hyperplastic polyp measuring greater than or equal to 1 cm in size.
• Traditional serrated adenomas found on the qualifying colonoscopy.
• Hyperplastic polyp measuring less than or equal to 1 cm in size found on the qualifying colonoscopy.
• Previous malignancies unless the patient has been disease-free for 5 or more years prior to randomization and is deemed by the physician to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: all in situ cancers and basal cell and squamous cell carcinoma of the skin.
• Colonoscopy performed after the qualifying colonoscopy but prior to randomization.
• Incomplete qualifying colonoscopy (e.g., cecum not visualized).
• Incomplete endoscopic excision of adenomatous polyps based on colonoscopist impression at qualifying colonoscopy. (Excision of all hyperplastic rectosigmoid polyps is not required.)
• Sub-total colectomy or total proctocolectomy. (Segmental resections are allowed.)
• Family history of CRC diagnosed at greater than or equal to 60 years of age in a first degree relative (mother, father, child, sibling) or in two first degree relatives with CRC at any age.
• Participants with a clinical diagnosis of a significant heritable risk for colorectal cancer (Familial Adenomatous Polyposis, Hereditary Nonpolyposis Colorectal Cancer [Lynch Syndrome]).
• Participants tested positive for a Familial Adenomatous Polyposis, Hereditary Nonpolyposis Colorectal Cancer [Lynch Syndrome] genetic mutation that increases risk of colorectal cancer.
• Inflammatory bowel disease (e.g., Crohn's Disease, ulcerative colitis).
• Life expectancy less than 10 years due to comorbid conditions in the opinion of the investigator.
• Other comorbid conditions that would prevent the participant from having colonoscopies or would prevent required follow-up.
Procedure: 5-year and 10 Year Surveillance Colonoscopy after Qualifying Colonoscopy
Adenocarcinoma of the Rectum, Adenocarcinoma of the Colon, Colon, Rectum
UT Southwestern
Durvalumab (MEDI4736) and Tremelimumab for Hepatocellular Carcinoma in Patients Listed for a Liver Transplant
Immunotherapy can safely downstage patients and achieve durable systemic disease control to improve clinical outcomes in HCC patients undergoing liver transplant.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Nicole Rich
126654
All
18 Years and over
Phase 2
NCT05027425
STU-2022-0746
Inclusion Criteria:
• Hepatocellular carcinoma, diagnosed either by biopsy or by combination of cirrhosis and imaging criteria (contrast-enhanced CT or MRI).
• Tumor within UCSF criteria for transplant: either one lesion ≤6.5 cm; or up to 3 lesions, none >4.5 cm, with a total diameter ≤8 cm, with no vascular invasion and no evidence of extrahepatic disease.
• Patient evaluated by institutional Liver Transplant team and listed for transplant.
• At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at baseline. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to randomization.
• No prior therapy for HCC at any time.
• Age ≥18 years at the time of study entry.
• ECOG score of 0 or 1
• Child-Pugh Score of 5, 6, or 7
• Body weight >30 kg
• Patients must have adequate organ and marrow function as defined in protocol
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
Exclusion Criteria:
• Extrahepatic disease.
• Variceal bleeding during 3 months prior to registration.
• Any autoimmune disease deemed a risk in the setting of immunotherapy per treating physician's judgment.
• Any other illness or patient condition deemed a medical or logistical barrier for protocol therapy per treating physician's judgment.
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Participation in another clinical study with an investigational product during the last 12 months Patients who have received other investigational agents previously who are no longer receiving these investigational agents may be eligible at the discretion of the PI.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• History of allogenic organ transplantation.
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician
• Patients with celiac disease controlled by diet alone
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
• History of leptomeningeal carcinomatosis
• History of active primary immunodeficiency
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
• Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine while receiving IP and up to 30 days after the last dose of IP.
• Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of durvalumab + tremelimumab combination therapy.
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
• Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.
• Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.
Drug: Durvalumab, Drug: Tremelimumab, Procedure: Liver Transplant
Hepatocellular Carcinoma, Cirrhosis, Portal Hypertension, Liver
Transplant
UT Southwestern
Safety and Efficacy of Atorvastatin v. Placebo on HCC Risk (TORCH)
Prospective randomized, multi-center, double blind placebo-controlled trial to assess the chemopreventive impact of atorvastatin (20 mg oral) vs placebo in up to 60 adults with advanced fibrosis at high risk of developing HCC.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yujin Hoshida
183525
ALL
18 Years and over
PHASE2
NCT05028829
STU-2022-0471
Inclusion Criteria:
• Willing and able to provide informed consent
• Male or female age \> 18 years at time of consent
• Clinically or histologically diagnosed advanced liver fibrosis or cirrhosis, as defined by one or more of the following: * Liver biopsy demonstrating advanced fibrosis or cirrhosis (METAVIR 3-4) * Fibroscan or MR elastography consistent with advanced fibrosis or cirrhosis * Imaging showing cirrhotic-appearing liver with signs of portal hypertension * Advanced fibrosis or cirrhosis documented clinically by a treating physician
• High-risk for HCC at screening according to the FIB-4 index
• PLSec score ≥ 3 measured in screening blood samples from the FIB-4-high individuals.
• Liver imaging within 6 months of Day 1 is required in cirrhotic subjects only, to exclude HCC
• Female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
• Willing and able to undergo protocol blood sampling
• Subject must be able to comply with dosing instructions for study drug administration and able to complete study schedule of assessments
Exclusion Criteria:
• Diagnosis of any of the following forms of chronic liver disease: * alpha-1-antitrypsin (A1AT) deficiency, Wilson disease, hemochromatosis, iron overload, prior known or suspected drug-induced liver injury (DILI) * Patients with PBC, PSC, AIH, or stable hemochromatosis may be included if their liver disease etiology overlaps with that of steatotic liver disease (SLD)
• Current or prior history of any of the following:
• Clinically significant illness or any other major medical disorder that in the opinion of the investigator, may interfere with subject treatment, assessment or compliance with the protocol
• Known positivity for HIV infection
• Active, untreated HCV infection
• Patients with prior history of HCV who achieved sustained virologic response (SVR) \>12 from Day 1 may be included in the study
• Uncontrolled chronic HBV
• Patients with well controlled disease with \>12 months of stable medication use (or no medication use, in those persons for whom anti-HBV therapy is not indicated)
• Clinical hepatic decompensation, defined as Child's Pugh class \>B7 or C cirrhosis
• Patients with Child's Pugh score of 7, class B, may be included in the study
• History of biliary diversion
• Solid organ transplant
• Malignancy within the 5 years prior to screening, with the exception of specific cancers that have been cured by surgical resection (basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible
• Pregnant or Nursing Females (a negative serum pregnancy test is required at screening for WOCBP)
• Life threatening SAE during the screening period
• Subjects having the following laboratory parameters at screening * ALT \> 10 x ULN * AST \> 10 x ULN * Hemoglobin \< 8.5 g/dl * Serum creatinine \> 2.0 mg/dL * CK \> 3x ULN
• Females who may wish to become pregnant and/or plan to undergo egg harvesting during the study and up to 30 days of the last dose of study drug
• WOCBP must abstain from breastfeeding and be willing to use effective birth control during through the week 4 post treatment follow-up visit
• Clinically relevant alcohol or drug abuse within 12 months of screening
• Use of any prohibited concomitant medications as described in Section 9.1.1
• Use of a statin medication within 90 days of Day 1 visit
• Subjects who are on a current statin at time of consent must be willing to undergo a 90-day washout period prior to randomization
• Known hypersensitivity to atorvastatin
• Current or planned participation in an investigational new drug (IND) trial from 30-days prior to randomization through the week 4 post treatment follow-up visit
DRUG: Atorvastatin 20mg, DRUG: Placebo
Cirrhosis, Liver Fibroses
Liver Disease, Chemoprevention, HCC, Atorvastatin
UT Southwestern
Safety Study of CC-93538 in Adult and Adolescent Participants With Eosinophilic Esophagitis
This study is an open-label, uncontrolled study design to evaluate the long-term safety and tolerability of treatment with CC-93538. The study will enroll participants who participated in the CC-93538-EE-001 or CC-93538-DDI-001 studies.
studyfinder@utsouthwestern.edu
ALL
12 Years to 75 Years old
PHASE3
NCT04991935
Inclusion Criteria:
* Previously participated in prior clinical study CC-93538-EE-001 and either:
• Subject experienced a severe EoE flare requiring endoscopic intervention and/or concomitant rescue therapy during the Induction Phase and has completed Week 24 of the Induction Phase; OR
• Subject completed the Induction Phase and does not qualify for entry to the Maintenance Phase for reasons other than a severe EoE flare; OR
• Subject experienced a severe EoE flare requiring endoscopic intervention and/or concomitant rescue therapy during the Maintenance Phase and completed Week 48 of the Maintenance Phase; OR
• Subject completed Week 48 of the Maintenance Phase * OR Subject must have participated in Study CC-93538-DDI-001 and completed assessments through the end of treatment visit * Demonstrated ≥ 80% and ≤ 120% overall compliance with required investigational product dosing during the prior studies. * Did not permanently discontinue investigational product in the prior studies and/or did not experience any clinically significant adverse events related to Investigational Product that would preclude further dosing in the opinion of the Investigator. * Females of childbearing potential must have a negative pregnancy test prior to the first dose of open-label CC-93538 and agree to practice a highly effective method of contraception (as defined in the prior study) until 5 months after the last dose of open-label CC-93538.
Exclusion Criteria:
* Clinical or endoscopic evidence of other diseases or conditions that may affect or confound the histologic, endoscopic, or clinical symptom evaluation for this study.
* Active Helicobacter pylori infection or esophageal varices.
* Evidence of immunosuppression, or of having received systemic immunosuppressive or immunomodulating drugs within 5 drug half-lives prior to open-label extension study (OLE) Day 1. Use of these agents is prohibited during the study.
* Treatment with oral or sublingual immunotherapy within 6 months of OLE Day 1. Use of these agents is prohibited during the study.
* Received an investigational product, other than that administered in the CC-93538-EE-001 or CC-93538-DDI-001 studies, within 5 half-lives prior to OLE Day 1 (includes investigational product received during an interventional trial for COVID-19). Those vaccinated with an investigational COVID-19 vaccine during the CC-93538-EE-001 or CC-93538-DDI-001 studies are not eligible to participate, unless allowed following a discussion with the Clinical Trial Physician.
* Received a live attenuated vaccine within one month prior to OLE Day 1; or anticipates the need for a live attenuated vaccine at any time throughout the course of this study.
* Any disease that would affect the conduct of the protocol or interpretation of the study results, or would put a patient at risk by participating in the study (e.g. colitis, celiac disease, Mendelian disorder associated with EoE, severe uncontrolled asthma, infection causing eosinophilia, hypereosinophilic syndrome, or cardiovascular condition, or neurologic or psychiatric illness that could compromise the participant's ability to accurately document symptoms of EoE; newly diagnosed malignancy, lymphoproliferative disease, or clinically significant laboratory abnormality).
* Active parasitic/helminthic infection or a suspected parasitic/helminthic infections or chronic infection (viral hepatitis, tuberculosis, or HIV)
* Has had idiopathic anaphylaxis or major immunologic reaction to an immunoglobulin-G containing agent; or any known hypersensitivity to any ingredient in CC-93538.
* Females who are pregnant or lactating. DRUG: CC-93538
Eosinophilic Esophagitis
Eosinophilic Esophagitis, CC-93538, RPC4046, Adult, Adolescent, Gastrointestinal Diseases, Esophagitis, Gastroenteritis, Eosinophils, Eosinophilia, Esophageal Diseases, Allergic Diseases, Antibody, Monoclonal, Hypersensitivity, Immunologic factors, Physiological Effects of Drugs, Cendakimab
Olanzapine Versus Megestrol Acetate for the Treatment of Loss of Appetite Among Advanced Cancer Patients
This phase III trial compares the effects of olanzapine versus megestrol acetate in treating loss of appetite in patients with cancer that has spread to other places in the body (advanced). Olanzapine may stimulate and increase appetite. This study aims to find out if olanzapine is better than the usual approach (megestrol acetate) for stimulating appetite and preventing weight loss.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Namrata Peswani
193600
All
18 Years and over
Phase 3
NCT04939090
STU-2021-1170
Inclusion Criteria:
• Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom)
• Diagnosis of advanced cancer
• Patient-reported 2-month weight loss of at least 5 pounds (2.3 kilograms) and/or physician-estimated caloric intake of less than 20 calories/kilogram of body weight per day
• The patient must perceive loss of appetite and/or weight as a problem; and have an appetite score of 4 or worse on the "Please rate your appetite…." question that requires a patient response on a 0-10 numeric rating scale
• Not receiving ongoing tube feedings or parenteral nutrition at the time of registration
• Not currently using systemic adrenal steroids (with the exception of short-term dexamethasone within 3 days of chemotherapy for control of chemotherapy side effects)
• No use of androgens, progesterone analogs, or other appetite stimulants within the past month
• Patient should not have poorly controlled hypertension or congestive heart failure at registration
• Patient should not have an obstruction of the alimentary canal, malabsorption, or intractable vomiting (defined as vomiting more than 3 times per day over the preceding week)
• Not currently using olanzapine for another medical condition or had previously used olanzapine for chronic nausea or for any pre-existing psychotic disorder
• Patient should not have had a previous blood clot at any time in the past
• No history of poorly controlled diabetes
• No symptomatic leptomeningeal disease or known brain metastases as these patients may have difficulty taking oral medications
• No history of hypersensitivity to olanzapine or megestrol acetate
• No COVID-19 infection in the past that, in the opinion of the treating physician, had left patients with compromised taste, which has not resolved at the time of registration
• Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done =< 14 days prior to registration is required
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
• Estimated life expectancy of 3 months or longer
• Serum creatinine =< 2.0 mg/dL
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN)
• Fasting glucose < 140 mg/dL
• Granulocytes > 1000/hpf
• No treatment with another antipsychotic agent, such as risperidone, quetiapine, clozapine, butyrophenone within 30 days of enrollment
• In order to complete the mandatory patient-completed measures, participants must be able to speak and/or read English or Spanish. Sites seeking to enroll Spanish-speaking patients should have access to Spanish speaking staff on site or through the use of a translation service to be able to conduct the informed consent discussion in Spanish, and to conduct the weekly phone calls
Exclusion Criteria:
• Psychiatric illness which would prevent the patient from giving informed consent
• Medical condition such as uncontrolled infection (including human immunodeficiency virus [HIV]), uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
• Patients who cannot swallow oral formulations of the agents
• Patients with impaired decision-making capacity (such as with a diagnosis of dementia or memory loss) are not eligible for this study
• No presence of a hormone-sensitive tumor, such as breast, endometrial, or prostate cancer (this exclusion criterion is intended to circumvent any confounding antineoplastic effects of megestrol acetate)
Drug: Olanzapine, Drug: Megestrol Acetate, Other: Questionnaire Administration
Lymphoma, Sarcoma, Anorexia, Multiple Myeloma, Mycosis Fungoides, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm, Brain and Nervous System, Other, Eye and Orbit, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Female, Breast - Male, Carcinoid Tumor, Cardiovascular, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, 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, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Leukemia, Other, Hodgkins Lymphoma, Heart, Kaposis sarcoma, Leukemia, Not Otherwise Specified, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Other Hematopoietic, Psychiatric Disorders, Small Intestine, Soft Tissue, Unknown Sites, Ill - Defined Sites
UT Southwestern
Study of XB002 in Subjects With Solid Tumors (JEWEL-101)
This is a Phase 1, open-label, multicenter, dose-escalation and expansion study evaluating the safety, tolerability, PK, pharmacodynamics, and clinical antitumor activity of XB002 administered IV q3w alone and in combination with nivolumab or bevacizumab to subjects with advanced solid tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Waddah Arafat
183526
All
18 Years and over
Phase 1
NCT04925284
STU-2023-0104
Inclusion Criteria:
• Cytologically or histologically and radiologically confirmed solid tumor that is inoperable, locally advanced, metastatic, or recurrent.
• Dose-Escalation Stage Cohorts A, AB and AN and Cohort-Expansion Stage (Cohorts B - M, BN, DB, FN and HN): The subject has received standard life-prolonging therapies unless they do not exist, or available therapies are intolerable or no longer effective.
• Cohort-Expansion Stage Cohort B and BN (Non-small Cell Lung Cancer): Subjects with Stage IV NSCLC who have documented radiographic disease progression during or following their last systemic anticancer therapy.
• Cohort-Expansion Stage Cohorts D and DB (Epithelial Ovarian Cancer): Subjects with high-grade serous ovarian cancer, including primary peritoneal cancer (PPC) and fallopian tube cancer (FTC) who have platinum-resistant disease following treatment with platinum-containing chemotherapy.
• Cohort-Expansion Stage Cohort E (Cervical Cancer): Subjects with persistent, recurrent, or metastatic carcinoma of the uterine cervix who have documented radiographic disease progression during or following their last systemic anticancer therapy.
• Cohorts F and FN (SCCHN): Subjects with head and neck cancer (squamous cell histology) who have documented radiographic disease progression during or following their last systemic anticancer therapy. Allowed primary tumor locations are oral cavity, oropharynx, hypopharynx, glottic larynx. Note: Excluded are subjects with primary tumor site of the nasopharynx.
• Cohort G (Pancreatic Cancer): Subjects with pancreatic cancer (adenocarcinoma histology) who have documented radiographic disease progression during or following their last systemic anticancer therapy.
• Cohorts H and HN (Esophageal SCC): Subjects with esophageal cancer (squamous cell histology) who have documented radiographic disease progression during or following their last systemic anticancer therapy. Note: subjects with esophageal adenocarcinoma and adenocarcinoma of gastroesophageal junction (GEJ) are excluded.
• Cohort I (mCRPC): Subjects with metastatic, castration resistant adenocarcinoma of the prostate. Note: Neuroendocrine differentiation and other histological features are permitted if adenocarcinoma is the primary histology.
• Cohort J (TNBC): Subjects with triple-negative (estrogen receptor negative [ER-]/progesterone receptor negative [PR-]/ human epidermal growth factor receptor 2 negative [HER-2-]) breast cancer who have documented radiographic disease progression during or following their last systemic anticancer therapy for inoperable locally advanced or metastatic disease.
• Cohort K (HR + BC): Subjects with breast cancer that is hormone receptor-positive (ER+ and/or PR+) and HER-2-) and who have documented radiographic disease progression during or following their last systemic anticancer therapy for inoperable locally advanced or metastatic disease.
• Cohort L (Endometrial Cancer): Subjects with advanced, recurrent or metastatic endometrial cancer who have documented radiographic disease progression during or following their last systemic anticancer therapy.
• Cohort M (Tumor-Agnostic Tissue Factor-Expressing Solid Tumors): Subjects with solid tumors other than those designated in Cohorts B-L and those which express tissue factor. Participation in this cohort will be at selected sites and countries based on site feasibility assessment.
• Expansion Cohorts: Subjects must have measurable disease per RECIST 1.1 as determined by the Investigator.
• Tumor tissue material collected approximately 2 years prior to consent. If archival tumor tissue is not available, a fresh tumor biopsy may be collected from subjects enrolled in the Dose-Escalation Stage and must be collected from subjects in the Cohort-Expansion Stage, at least 7 days (and up to 60 days) prior to first dose.
• Recovery to baseline or ≤ Grade 1 severity (Common Terminology Criteria for Adverse Events version 5 [CTCAE v5]) from AEs.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
• Adequate organ and marrow function.
• Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception.
• Female subjects of childbearing potential must not be pregnant at screening.
Exclusion Criteria:
• Receipt of prior therapies as defined in study protocol
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment.
• Uncontrolled, significant intercurrent or recent illness.
• Major surgery within 4 weeks before first dose of study treatment
• Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per electrocardiogram (ECG).
• Pregnant or lactating females
• Previously identified allergy or hypersensitivity to components of study treatment formulations or history of severe infusion-related reactions to monoclonal antibodies.
• Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial non-melanoma cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.
Drug: XB002, Drug: Nivolumab, Drug: Bevacizumab
Endometrial Cancer, Pancreatic Cancer, Cervical Cancer, Non Small Cell Lung Cancer, Triple Negative Breast Cancer, Epithelial Ovarian Cancer, Breast - Female, Breast - Male, Esophagus, Lung/Thoracic, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Urinary, Ovary, Pancreas, Prostate, Metastatic Castration-resistant Prostate Cancer, SCCHN, Esophageal SCC, Hormone Receptor-positive Breast Cancer, Tissue Factor-Expressing Solid Tumors
ADC, Antibody drug conjugate, Tissue Factor, Auristatin, Nivolumab, Bevacizumab
UT Southwestern
PLAN Intervention to Enhance Engagement of Latino Cancer Patients in Advanced Care Planning
This trial tests whether Planning for Your Advance Care Needs (PLAN) intervention works to enhance Latino patients' understanding of and engagement in advanced care planning. The PLAN intervention may be an effective method to help people with cancer plan for and talk about advance care planning (the care they would want if they were unable to communicate) with their loved ones and doctors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Mary Paulk
41481
All
18 Years and over
N/A
NCT04889144
STU-2021-0192
Inclusion Criteria:
• Identifying ethnically as Latino.
• Locally advanced or metastatic cancer and/or have experienced disease progression on at least first-line chemotherapy.
• Ability to provide informed consent.
Exclusion Criteria:
• Not fluent in English or Spanish.
• Severely cognitively impaired (as measured by Short Portable Mental Status Questionnaire scores of >= 6 to be delivered by trained study research staff during screening).
• Too ill or weak to complete the interviews (as judged by interviewer).
• Currently receiving palliative care/hospice at the time of enrollment (to allow prediction of [advanced care planning] ACP).
• Children and young adults under age 18.
• Patients deemed inappropriate for the study by their treating oncologist.
Other: Communication Intervention, Other: Best Practice, Other: Questionnaire Administration
Lymphoma, Sarcoma, Metastatic Malignant Solid Neoplasm, Cervix, Colon, Esophagus, Gall Bladder, Head and Neck, Liver, Lung/Thoracic, Other Female Genital, Other Urinary, Ovary, Pancreas, Stomach, Locally Advanced Malignant Solid Neoplasm
advance care planning, Latinos, communication
UT Southwestern; Parkland Health & Hospital System
TReatment for ImmUne Mediated PathopHysiology (TRIUMPH)
TReatment for ImmUne Mediated PathopHysiology (TRIUMPH) is a multi-center, three arm, randomized, controlled trial of immunosuppressive therapy for children with acute liver failure. The study will determine if suppressing inflammatory responses with either corticosteroids or equine anti-thymocyte globulin therapy improves survival for children with this rare, life-threatening condition.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Mia.Hamilton@UTSouthwestern.edu
Norberto Rodriguez-Baez
50856
ALL
1 Year to 18 Years old
PHASE2
NCT04862221
STU-2022-0154
Inclusion Criteria:
• Patient with liver injury of ≤ 6 weeks duration resulting in an international normalized ratio (INR) of ≥ 1.5 and \< 2.0 (not corrected by vitamin K) with evidence of hepatic encephalopathy (HE) or INR ≥ 2.0 without evidence of HE.
• Age is greater than or equal to 1 year and less than 18 years of age.
• Patient or their legally authorized representative(s) (LAR) must consent (and assent, if applicable) to be in the study and must have signed and dated an approved informed consent form which conforms to federal and institutional guidelines.
• Females of reproductive potential should not plan on conceiving children during the study and must agree to use a medically accepted form of contraception.
Exclusion Criteria:
• Evidence of active infection with Hepatitis A, B, C, E or evidence of acute herpes simplex virus (HSV) or adenovirus infection
• Travel within the past 3 months to an area highly endemic for Hepatitis E
• Diagnosis of hemophagocytic lymphohistiocytosis (HLH) Note: Patients with a history of consanguinity and/or central nervous system (CNS) dysfunction that is exaggerated compared to the degree of liver dysfunction (as judged by the site investigator) will not be enrolled until results of rapid genetic testing are available. Turn-around time for genetic testing results is estimated to be 72-96 hours.
• Aplastic anemia as defined by standardized criteria \[1\] diagnosed prior to enrollment
• Diagnosis of autoimmune Hepatitis (AIH)
• Diagnosis of acute Wilson disease
• Diagnosis of inborn error of metabolism Note: Suspicion of metabolic disease is not an exclusion for entry into the Trial.
• Diagnosis of acute drug or toxin-induced liver injury
• History of recreational drug use within the past 4 weeks
• Therapy with an immunosuppressive agent, including chemotherapy, biological therapies or an experimental drug or device within the past 6 weeks
• Liver injury due to ischemia
• Liver dysfunction diagnosed more than 6 weeks prior to screening
• History of allergy to horse dander
• Sepsis
• Imminent risk of death as judged by the clinical site investigator, including but not limited to; signs of cerebral herniation at the time of enrollment and presence of intractable arterial hypotension
• Solid organ or stem cell transplant recipient
• Pregnant or breast-feeding at the time of proposed study entry
• Clinical AIDS or HIV positive
• History of any form of malignant neoplasm and/or tumors treated within five years prior to study entry (other than non-melanoma skin cancer or in situ cervical cancer) or where there is current evidence of recurrent or metastatic disease
• Received a live-virus vaccine within 4 weeks of study entry
• Positive test result for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
• Psychiatric or addictive disorders that would preclude obtaining informed consent/assent
• Patient is unwilling or unable to adhere with study requirements and procedures
• Currently receiving other experimental therapies
DRUG: High-dose methylprednisolone, DRUG: Equine anti-thymocyte globulin, DRUG: Prednisolone, DRUG: Placebo for prednisolone, DRUG: Placebo for infusions, DRUG: Diphenhydramine, DRUG: Methylprednisolone
Hepatic Encephalopathy, Acute Liver Failure, Fulminant Hepatic Failure, Acute Liver Injury, Immune Dysregulation
hepatic insufficiency, liver diseases, liver failure, anti-thymocyte agents
Children’s Health
Pancreatic Cancer Early Detection Consortium (PRECEDE)
The purpose of the Pancreatic Cancer Early Detection (PRECEDE) Consortium is to conduct research on multiple aspects of early detection and prevention of pancreatic ductal adenocarcinoma (PDAC) by establishing a multisite cohort of individuals with family history of PDAC and/or individuals carrying pathogenic/likely pathogenic germline variants (PGVs) in genes linked to PDAC risk for longitudinal follow up.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Nisa Kubiliun
70567
ALL
18 Years to 90 Years old
NCT04970056
STU-2023-0039
Inclusion Criteria:
Individuals from the following groups who present for clinical evaluation and assessment of PDAC risk at any of the participating sites can be offered participation in the PRECEDE database:
Cohort 1
Individuals without history of PDAC meeting any of the following criteria:
• 2+ relatives with PDAC on same side of family where 2 affected are first degree related to each other and at least 1 affected is first degree related to subject; age 50+ or ≤10 years younger than earliest PDAC in family at time of diagnosis.
• 2 affected first degree relatives with PDAC; age 50+ or 10 years younger than earliest PDAC in family
• BRCA1, BRCA2, PALB2, ATM, MLH1, MSH2, MSH6, PMS2, EPCAM pathogenic or likely pathogenic variant AND 1 first or second degree relative with PDAC; age 50+ or 10 years younger than earliest PDAC in family
• Familial Atypical Moles and Malignant Melanoma (FAMMM) with pathogenic or likely pathogenic CDKN2A variant; age 40+
• Peutz-Jegher syndrome with STK11 pathogenic or likely pathogenic variant; age 35+
• Hereditary pancreatitis with PRSS1 pathogenic or likely pathogenic variant and history of pancreatitis; age 40+ Cohort 2 Individuals without history of PDAC meeting any of the following criteria:
• ATM, BRCA1, BRCA2, or PALB2 pathogenic or likely pathogenic variant regardless of family history, age 50+
• 2+ relatives with PDAC on the same side of family, any degree of relation, not meeting other criteria above; age 50+ or 10 years younger than earliest PDAC in family
• 1 first degree relative with PDAC ≤ age 45; age up to 10 years younger than PDAC diagnosis in family member Cohort 3 Individual meeting criteria for Cohorts 1 or 2 EXCEPT age (i.e. too young to qualify for Cohorts 1 or 2) Cohort 4 Individuals without history of PDAC presenting for evaluation who do not meet any criteria for 1-3, 6, or the Cyst Cohort. Cohort 5 Individuals without history of PDAC who are not otherwise engaged in pancreas surveillance at a participating site may be invited to participate in the PRECEDE database and to donate a biosample (e.g. blood, saliva, and/or buccal swab) for discovery studies. This may include relatives of individuals in Cohorts 1-4,6, and the Cyst Cohort. Cohort 6 Individuals with a personal history of PDAC meeting any of the following criteria:
• Family history includes at least one first degree relative with PDAC, or 2 relatives with PDAC who are first degree related to each other
• Personal or family history of a pathogenic or likely pathogenic germline variant in ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2,PMS2, PRSS1, STK11
• Diagnosed ≤ age 45 Cyst Cohort Individuals with a personal history of a pancreatic cystic neoplasm not meeting any criteria for Cohorts 1-3 or 6 (no known family history of PDAC, no known pathogenic germline variants linked to PDAC risk)
Exclusion Criteria:
* Individuals not meeting the criteria above. Pancreatic Ductal Adenocarcinoma, Pancreas Cancer, Pancreas Cyst, Genetic Predisposition
UT Southwestern
Research Study on Whether Semaglutide Works in People With Non-alcoholic Steatohepatitis (NASH) (ESSENCE)
Semaglutide is a medicine studied in patients with NASH. Semaglutide is a well-known medicine, which is already used by doctors to treat type 2 diabetes in many countries. Participants will either get semaglutide or a dummy medicine - which treatment participants get is decided by chance. Participants will need to inject themselves with medicine under the skin. Participants will need to do this once a week. The study will last for about 5 years. Participants will have up to 21 clinic visits and 9 phone calls with the clinical staff during the study. Some of the clinic visits may be spread over more than one day. Participants with other chronic liver diseases cannot take part in this study. Women cannot take part in the study if they are pregnant, breast-feeding or plan to become pregnant during the study period.
studyfinder@utsouthwestern.edu
ALL
18 Years and over
PHASE3
NCT04822181
Inclusion Criteria:
* Age above or equal to 18 years at the time of signing informed consent.
* Histological evidence of NASH based on a central pathologist evaluation of the baseline liver biopsy. The baseline liver biopsy can be a historical biopsy obtained within 180 days prior to the screening visit (V1).
* Histological evidence of fibrosis stage 2 or stage 3 according to the NASH CRN (Clinical Research Network) classification based on a central pathologist evaluation of the baseline liver biopsy.
* A histological NAS (Non-alcoholic fatty liver disease Activity Score) above or equal to 4 with a score of 1 or more in steatosis, lobular inflammation and hepatocyte ballooning based on a central pathologist evaluation of the baseline liver biopsy.
Exclusion Criteria:
* Documented causes of chronic liver disease other than non-alcoholic fatty liver disease (NAFLD)
* Positive HBsAg, positive anti-HIV, positive HCV RNA at screening (V2A) or any known presence of HCV RNA or HBsAg within 2 years of screening (V2A).
* Presence or history of ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis or liver transplantation at randomisation.
* Known or suspected excessive consumption of alcohol (greater than 20 g/day for women or greater than 30 g/day for men) or alcohol dependence (assessed by the Alcohol Use Disorders Identification Test (AUDIT questionnaire)).
* Treatment with vitamin E (at doses greater than or equal to 800 IU/day) or pioglitazone or medications approved for treatment of NASH which has not been at a stable dose in the period from 90 days prior to the screening visit (V2A). In addition, for subjects with historical liver biopsies taken more than 90 days prior to screening, treatment should be at a stable dose from time of biopsy until screening.
* Treatment with GLP-1 RAs in the period from 90 days prior to the screening visit (V2A). In addition, for subjects with historical liver biopsies taken more than 90 days prior to screening, any treatment with GLP-1 RAs from time of biopsy until screening (V2A).
* Treatment with glucose-lowering agent(s) (other than GLP-1 RAs), lipid-lowering medication or weight loss medication not stable in the opinion of the investigator in the period from 90 days prior to the screening visit (V2A). In addition, for subjects with historical liver biopsies taken more than 90 days prior to screening, treatment should be at a stable dose in the opinion of the investigator from time of biopsy until screening. DRUG: Semaglutide, DRUG: Placebo
Non-alcoholic Steatohepatitis
Testing the Combination of Two Anti-cancer Drugs, DS-8201a and AZD6738, for The Treatment of Patients With Advanced Solid Tumors Expressing the HER2 Protein or Gene, The DASH Trial
The dose escalation phase of this trial identifies the safety, side effects and best dose of ceralasertib (AZD6738) when given in combination with trastuzumab deruxtecan (DS-8201a) in treating patients with solid tumors that have a change (mutation) in the HER2 gene or protein and have spread to other places in the body (advanced). The dose expansion phase (phase Ib) of this trial compares how colorectal and gastroesophageal cancers with HER2 mutation respond to treatment with a combination of ceralasertib and trastuzumab deruxtecan versus trastuzumab deruxtecan alone. Ceralasertib may stop the growth of tumor cells and may kill them by blocking some of the enzymes needed for cell growth. Trastuzumab deruxtecan is a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive cancer cells in a targeted way and delivers deruxtecan to kill them. Ceralasertib and trastuzumab deruxtecan may be safe, tolerable and effective in treating patients with advanced solid tumors expressing the HER2 protein or gene.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
177531
ALL
18 Years and over
PHASE1
NCT04704661
STU-2023-0128
Inclusion Criteria:
* DOSE-ESCALATION PHASE: Must have histologically confirmed advanced solid tumor including but not restricted to breast cancer, gastric or gastroesophageal cancer, colon cancer, endometrial cancer, salivary gland tumors, and hepatobiliary tumors
* DOSE-EXPANSION PHASE: Must have histologically confirmed advanced/metastatic gastroesophageal cancer (cohort A) or colorectal cancer (cohort B)
* DOSE-EXPANSION PHASE: Patients must have a biopsiable lesion and provide consent for on treatment biopsy
* Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of AZD6738 in combination with DS-8201a in patients \< 18 years of age, children are excluded from this study
* Patients must have HER2-positive or HER2-expressing tumors determined by a Clinical Laboratory Improvement Act (CLIA)-certified laboratory. As a rule, for HER2 immunohistochemistry (IHC) scoring system trastuzumab for gastric cancer (TOGA) criteria used for gastric/gastroesophageal junction (GEJ) cancers will be employed (Note: in escalation phase, for breast cancer patients that are included, breast cancer criteria can be used). Specific requirement of HER2 status is outlined below:
* HER2 expression (1-3+) by IHC locally and confirmed centrally OR
* HER2 expression (1-3+) by IHC tested centrally OR
* HER2 amplification based on fluorescence in situ hybridization (FISH) or next generation sequencing
* Must have received at least one line of systemic chemotherapy for either locally advanced or metastatic disease and should have either progressed on this therapy or been intolerant to this therapy
* For tumors where anti-HER2 therapy is standard of care, patients must have progressed on at least 1 line of anti-HER2 therapy if eligible. For patients where DS8201a is approved as standard of care, prior treatment with DS8201a is not allowed
* Must have unresectable, advanced/metastatic disease
* Must have at least 1 measurable lesion on CT scan per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Patient without measurable but evaluable disease are allowed for dose-escalation phase
* Must be willing and able to provide an adequate archival tumor sample available to confirm HER2 status by Central Laboratory (if local testing is used for enrollment), else must be willing and able to provide an adequate archival tumor sample for HER2 testing centrally
* Must have Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
* Must have life expectancy of at least 3 months
* Must have left ventricular ejection fraction (LVEF) \>= 50% within 28 days before enrollment (study drug treatment) by either an echocardiogram (ECHO) or multigated acquisition (MUGA) scan
* Must have a negative pregnancy test (if female)
* Platelets \>= 100,000/mcL (within 14 days before enrollment)
* No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment
* Hemoglobin \>= 9.0 g/dL (within 14 days before enrollment)
* Absolute neutrophil count \>= 1,500/mcL (within 14 days before enrollment)
* No administration of granulocyte colony-stimulating factor (G-CSF) is allowed within 1 week prior to screening assessment
* Creatinine clearance \> 45/mL/min (using the Cockcroft-Gault equation) (within 14 days before enrollment)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 x institutional upper limit of normal (ULN) (within 14 days before enrollment)
* Total bilirubin =\< 1.5 x ULN if no liver metastases or \< 3 x ULN with Gilbert's Syndrome or liver metastases at baseline (within 14 days before enrollment)
* Leukocytes \>= 3,000/mcL (within 14 days before enrollment)
* Albumin \> 2.5 g/dL (GEJ patients only) (within 14 days before enrollment)
* International normalized ratio (INR) and either partial thromboplastin time (PTT) or activated (a)PTT =\< 1.5 x ULN (within 14 days before enrollment)
* Must have adequate treatment washout period before study treatment, defined as: Major surgery (\>= 4 weeks), radiation therapy (\>= 3 weeks; in case of palliative radiation \>= 2 weeks), systemic therapy (\>= 3 weeks; in case of investigational drug use \>= 2 weeks or 5 half-lives, whichever is longer)
* Patients who are human immunodeficiency virus (HIV) positive may participate IF they meet the following eligibility requirements:
* They must be stable on their anti-retroviral regimen, and they must be healthy from an HIV perspective
* They must have a CD4 count of greater than 250 cells/mcL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count \< 200 cells/mcl over the past 2 years, unless it was deemed related to THE CANCER AND/OR CHEMOTHERAPY-induced bone marrow suppression
* For patients who have received chemotherapy in the past 6 months, a CD4 count \< 250 cells/mcl during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy
* They must have an undetectable viral load and a CD4 count \>= 250 cells/mcL within 7 days of enrollment
* They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months. HIV-infected patients should be monitored every 12 weeks for viral load and CD4 counts
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Subjects with clinically inactive brain metastases may be included. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole-brain radiation therapy and study treatment
* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate central nervous system (CNS) specific treatment is not required and is unlikely to be required for at least 4 weeks (or scheduled assessment after the first cycle of treatment), and a risk-benefit analysis (discussion) by the patient and the investigator favors participation in the clinical trial
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* HER2 antibody conjugated to a topoisomerase 1 inhibitor agents as well as AZD6738 are known to be teratogenic; thus, women of child-bearing potential 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 at least 7 months (women of childbearing potential \[WOCBP\] only) after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of study drug administration
* Women of non-child-bearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle-stimulating hormone \[FSH\] \> 40 mIU/mL and estradiol \< 40 pg/mL \[\< 147 pmol/L\] is confirmatory) are eligible. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods outlined for women of child-bearing potential if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method
* Male subjects must not freeze or donate sperm starting at screening and throughout the study period, and at least 6 months after the final study drug administration. Preservation of sperm should be considered prior to enrolment in this study
* Female subjects must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the final study drug administration
* Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible
Exclusion Criteria:
* Patients with a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. Patient using e-cigarettes/vaping are also excluded
* Patients with a medical history of myocardial infarction within 6 months before enrollment (study treatment), symptomatic congestive heart failure (New York Heart Association Class II to IV, corrected QT interval (QTcF) prolongation to \> 470 ms (females) or \> 450 ms (males) as corrected by Framingham's formula
* Patients with spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms
* Patients with multiple primary malignancies within 2 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other curatively treated solid tumors
* Patients with a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product
* Patients with an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
* Patients with substance abuse or any other medical conditions that would increase the safety risk to the subject or interfere with participation of the subject or evaluation of the clinical study in the opinion of the investigator
* Patients with a concomitant medical condition that would increase the risk of toxicity in the opinion of the investigator
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities grade \>1) with the exception of alopecia. Subjects with chronic grade 2 toxicities may be eligible per discretion of the investigator after discussion with study principal investigator (PI) (e.g., grade 2 chemo-induced neuropathy).
* Any previous treatment with an ATR inhibitor
* Patients with any clinically apparent pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within three months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease \[COPD\], restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement (i.e., Rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy
* Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
* Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
* Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir). The required washout period prior to starting study treatment is 2 weeks. Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents
* Patients with a pleural effusion, ascites, or pericardial effusion that requires drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy (CART). (Drainage and CART are not allowed within 2 weeks prior to screening assessment)
* Patients with previous allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
* Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable within the last 28 days as long as they are not within 1 week prior to screening assessment)
* Patients at risk of brain perfusion problems, e.g., medical history of carotid stenosis or pre-syncopal or syncopal episodes, history of transient ischemic attacks (TIAs)
* Uncontrolled hypertension (grade 2 or above) requiring clinical intervention
* Patients with relative hypotension (\< 90/60 mm Hg) or clinically relevant orthostatic hypotension, including a fall in blood pressure of \> 20 mm Hg
* Patients who have received corticosteroids (at a dose \> 10 mg prednisone/day or equivalent) for any reason within 2 weeks prior to first dose
* Patients with uncontrolled intercurrent illness
* Patients with psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are excluded from this study because DS-8201a is a HER2 antibody conjugated to a topoisomerase 1 inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with DS-8201a, breastfeeding should be discontinued if the mother is treated with DS-8201a. These potential risks may also apply to AZD6738
* Patients cannot be receiving chloroquine or hydroxychloroquine. Patients receiving these drugs must have a washout period of \> 14 days before enrollment/randomization PROCEDURE: Biopsy, PROCEDURE: Biospecimen Collection, DRUG: Ceralasertib, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography, PROCEDURE: Multigated Acquisition Scan, PROCEDURE: Positron Emission Tomography, BIOLOGICAL: Trastuzumab Deruxtecan
Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, Metastatic Breast Carcinoma, Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8, Stage III Colon Cancer AJCC v8, Stage IV Colon Cancer AJCC v8, Advanced Endometrial Carcinoma, Clinical Stage IV Gastric Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Unresectable Malignant Solid Neoplasm, Stage III Uterine Corpus Cancer AJCC v8, Stage IV Uterine Corpus Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8, Metastatic Gastroesophageal Junction Adenocarcinoma, Stage III Colorectal Cancer AJCC v8, Advanced Breast Carcinoma, Advanced Colon Carcinoma, Advanced Colorectal Carcinoma, Advanced Gastric Carcinoma, Advanced Gastroesophageal Junction Adenocarcinoma, Advanced Salivary Gland Carcinoma, Clinical Stage III Gastric Cancer AJCC v8, HER2-Positive Breast Carcinoma, Malignant Hepatobiliary Neoplasm, Stage III Major Salivary Gland Cancer AJCC v8, Stage IV Colorectal Cancer AJCC v8, Stage IV Major Salivary Gland Cancer AJCC v8, Unresectable Colorectal Carcinoma, Unresectable Gastroesophageal Junction Adenocarcinoma
UT Southwestern
Ultra-fractionated Radiotherapy for Rectal Cancer
The rationale of this clinical trial is to assess the feasibility of selective non-operative management for locally advanced rectal cancer using dose-escalated ultra-fractionated short course radiation therapy interdigitated with chemotherapy. We believe delivering short course radiotherapy over a prolonged interval, at escalated doses and with concurrent chemotherapy may be feasible and allow for improved clinical response.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Nina Sanford
181796
All
18 Years and over
Phase 1
NCT04677413
STU-2020-1394
Inclusion Criteria:
• At least 18 years of age. Both men and women and members of all races and ethnic groups will be included.
• Willing and able to provide written informed consent
• Pathologic diagnosis of rectal adenocarcinoma
• T3-4 and/or N+ disease per AJCC 8th edition
• No prior treatment for rectal adenocarcinoma
• Eastern Cooperative Group (ECOG) performance status of 0-2.
• Laboratory values supporting acceptable organ and marrow function within 30 days of eligibility confirmation. Defined as follows:
• WBC ≥ 3,000/mL;
• ANC WBC ≥ 1,000/mL;
• PLT ≥ 75,000/mL;
• T Bili ≤ 1.5 x upper limit of normal (ULN);
• AST/ALT ≤ 2.5 x ULN;
• Creatinine not above ULN, or creatinine clearance >50 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal.
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) starting with the first dose of study therapy through 90 days after the last dose of study drugs. 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).
Exclusion Criteria:
• Distant nodal disease (retroperitoneal nodes) including inguinal nodes, or any metastatic disease by CT.
• Prior RT to the pelvis.
• Uncontrolled comorbid illness or condition including congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric illness that would limit compliance with the study requirements.
• Psychiatric illness/social situations that would limit consenting and compliance with study requirements.
• Participants who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants
Radiation: Ultrafractionated radiotherapy for rectal cancer
Rectal Cancer, Rectum
Rectal Cancer,T3-4 or N+
UT Southwestern; Parkland Health & Hospital System
Comparison of Chemotherapy Before and After Surgery Versus After Surgery Alone for the Treatment of Gallbladder Cancer
This phase II/III trial compares the effect of adding chemotherapy before and after surgery versus after surgery alone (usual treatment) in treating patients with stage II-III gallbladder cancer. Chemotherapy drugs, such as gemcitabine 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. Giving chemotherapy before surgery may make the tumor smaller; therefore, may reduce the extent of surgery. Additionally, it may make it easier for the surgeon to distinguish between normal and cancerous tissue. Giving chemotherapy after surgery may kill any remaining tumor cells. This study will determine whether giving chemotherapy before surgery increases the length of time before the cancer may return and whether it will increase a patient's life span compared to the usual approach.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Matthew Porembka
155238
ALL
18 Years and over
PHASE2
NCT04559139
STU-2021-0113
Inclusion Criteria:
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Patient must have histologically-confirmed T2 or T3 gallbladder cancer discovered incidentally at the time of or following routine cholecystectomy for presumed benign disease
* NOTE: Patients with histologically-confirmed Tis, T1a, T1b, or T4 tumors are not eligible
* Patient must have undergone initial cholecystectomy within 12 weeks prior to randomization
* Patient must have the ability to understand and the willingness to sign a written informed consent document
* Leukocytes \>= 3,000/mcL (obtained =\< 28 days prior to randomization)
* Absolute neutrophil count \>= 1,500/mcL (obtained =\< 28 days prior to randomization)
* Platelets \>= 100,000/mcL (obtained =\< 28 days prior to randomization)
* Total bilirubin =\< institutional upper limit of normal (ULN) except in patients with Gilbert's syndrome. Patients with Gilbert's syndrome are eligible if direct bilirubin \< 1.5 x ULN of the direct bilirubin (obtained =\< 28 days prior to randomization)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (obtained =\< 28 days prior to randomization)
* Serum creatinine =\< institutional ULN OR creatinine clearance \>= 50 mL/min/1.73 m\^2 (Based on Cockcroft Gault estimation) (obtained =\< 28 days prior to randomization)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* 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
Exclusion Criteria:
* Patient must not have any evidence of metastatic disease or inoperable loco-regional disease based on high-quality, preoperative, cross-sectional imaging (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) of the chest, abdomen, and pelvis (C/A/P) obtained within 6 weeks prior to randomization, defined as
* No radiographic evidence of distant disease (M1 disease)
* No radiographic evidence of tumor invasion into multiple extrahepatic organs (T4 disease)
* No radiographic evidence of distant lymph node involvement (celiac, para-aortic, para-caval lymph nodes)
* No evidence of new-onset ascites
* Soft tissue thickening within or in direct communication with the gallbladder fossa, peri-portal lymph node involvement, involvement of one extrahepatic organ, and other disease within the confines of what constitutes 'localized resectable' disease are allowable
* Women must not be pregnant or breast feeding due to the potential harm to unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All females of child bearing potential must have a serum or urine pregnancy test to rule out pregnancy within 14 days prior to randomization. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) 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 not expect to conceive or father children by being strongly advised to use accepted and effective method(s) of contraception or to abstain from sexual intercourse for the duration of their participation in the study DRUG: Cisplatin, DRUG: Gemcitabine Hydrochloride, PROCEDURE: Lymphadenectomy, PROCEDURE: Partial Hepatectomy
Stage III Gallbladder Cancer AJCC v8, Stage IIIA Gallbladder Cancer AJCC v8, Stage IIIB Gallbladder Cancer AJCC v8, Stage II Gallbladder Cancer AJCC v8, Stage IIA Gallbladder Cancer AJCC v8, Stage IIB Gallbladder Cancer AJCC v8
UT Southwestern; Parkland Health & Hospital System
Comparing the Outcome of Immunotherapy-Based Drug Combination Therapy With or Without Surgery to Remove the Kidney in Metastatic Kidney Cancer, the PROBE Trial (PROBE)
This phase III trial compares the effect of adding surgery to a standard of care immunotherapy-based drug combination versus a standard of care immunotherapy-based drug combination alone in treating patients with kidney cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, pembrolizumab, and avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Surgery to remove the kidney, called a nephrectomy, is also considered standard of care; however, doctors who treat kidney cancer do not agree on its benefits. It is not yet known if the addition of surgery to an immunotherapy-based drug combination works better than an immunotherapy-based drug combination alone in treating patients with kidney cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
42296
All
18 Years and over
Phase 3
NCT04510597
STU-2021-0266
Inclusion Criteria:
• STEP 1 REGISTRATION: Participants must have a histologically proven diagnosis of clear cell or non-clear cell renal cell carcinoma. Participants with collecting duct carcinoma histology are not eligible. Participants with multifocal or bilateral tumors are eligible
• STEP 1 REGISTRATION: Participants must have primary tumor in place
• STEP 1 REGISTRATION: Participants must have the following scans performed, showing clinical evidence of measurable or non-measurable metastatic disease:
• Computed tomography (CT) scan of the chest (can be performed without contrast if CT contrast cannot be given)
• CT of abdomen and pelvis with contrast OR magnetic resonance imaging (MRI) of the abdomen and pelvis with or without contrast Scans must be performed within the following timeframes:
• Treatment naive participants must have scans documenting metastatic disease completed within 90 days prior to study registration
• Previously treated participants must have scans documenting metastatic disease completed within 90 days prior to first dose of systemic treatment
• STEP 1 REGISTRATION: Participants with symptomatic metastases may have received palliative radiotherapy or receive palliative radiotherapy after registration
• STEP 1 REGISTRATION: Participants must have no clear contraindications to nephrectomy
• STEP 1 REGISTRATION: Participants must be offered the opportunity to participate in specimen bank. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
• STEP 1 REGISTRATION: Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
• STEP 1 REGISTRATION: As part of the Oncology Patient Enrollment Network (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: Participants must have at least one of the following scans performed 12 weeks (+/- 2 weeks) after starting pre-randomization treatment
• CT scan of the chest (can be performed without contrast if CT contrast cannot be given)
• CT of abdomen and pelvis with contrast OR MRI of the abdomen and pelvis with or without contrast Scans must be performed within 28 days prior to randomization. Response should be assessed by comparing with a CT or MRI of the chest, abdomen and pelvis obtained prior to starting pre-randomization treatment. Participants with complete response in all metastatic sites are not eligible to randomize to Step 2 • STEP 2 REGISTRATION: Participants must have one of the following objective statuses after 12 weeks of pre-randomization treatment
• Stable disease
• Partial response
• The treating investigator believes the patient is deriving clinical benefit from systemic therapy AND have Zubrod performance status 0-1
• STEP 2 REGISTRATION: Participants must plan to continue the immune-based therapy received during pre-randomization treatment
• STEP 2 REGISTRATION: Participants must be randomized on or between the 11th and 14th week of protocol-directed pre-randomization treatment therapy
• STEP 2 REGISTRATION: Participants must have received at least one of the minimum amounts of immunotherapy:
• 2 infusions of nivolumab + 1 infusion of ipilimumab
• 2 infusions of pembrolizumab
• 2 infusions of avelumab
• STEP 2 REGISTRATION: Participants must have a planned surgery date within 42 days of randomization
• STEP 2 REGISTRATION: Participants must be a surgical candidate as determined by study urologist. The urology consult should be done within 42 days prior to randomization
• STEP 2 REGISTRATION: Participants must have a complete physical examination and medical history within 28 days prior to randomization
• STEP 2 REGISTRATION: Participants must have a Zubrod performance status of 0-1 within 28 days prior to randomization
• STEP 2 REGISTRATION: Total bilirubin =< institutional upper limit of normal (ULN) (within 28 days prior to randomization)
• STEP 2 REGISTRATION: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutional upper limit of normal (ULN) (within 28 days prior to randomization)
• STEP 2 REGISTRATION: Serum creatinine =< 1.5 x the institutional upper limit of normal (IULN) OR measured OR calculated creatinine clearance >= 50 mL/min using the Cockcroft-Gault Formula) (must have been drawn and processed within 28 days prior to randomization)
Exclusion Criteria:
• STEP 1 REGISTRATION: Participants must not have known active brain metastases. Participants with previously treated brain metastases are eligible if participant has no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies are not required. If brain imaging studies are performed, they must be negative for disease
• STEP 1 REGISTRATION: Participants must not have received the following prior treatment of metastatic renal cell carcinoma:
• Treatment naive participants must not have received any prior lines of systemic therapy for metastatic renal cell carcinoma beyond the line intended as part of protocol therapy
• Previously treated participants must not have received any systemic therapy for metastatic renal cell carcinoma beyond the one regimen received off protocol as specified in Step 1 pre-randomization treatment
• STEP 1 REGISTRATION: Participants must not have received more than the following amounts protocol-directed pre-randomization treatment:
• Treatment naive participants must not have received any pre-randomization treatment.
• Previously treated participants must not be planning to receive any additional treatment prior to Step 2 randomization, and must not have received more than the following amounts of pre-randomization treatment:
• 4 infusions of nivolumab
• 4 infusions of ipilimumab
• 4 infusions of pembrolizumab
• 7 infusions of avelumab
• STEP 1 REGISTRATION: Participants must not have received immunotherapy for any cancer within the following timeframes:
• Treatment naive participants must not have received any immunotherapy within a year of registration
• Previously treated participants must not have received any other immunotherapy within a year of the start of off protocol specified pre-randomization treatment
• STEP 1 REGISTRATION: Participants must not have a solitary kidney and not have a transplanted kidney
• STEP 1 REGISTRATION: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, any in situ or T1 cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for at least two years
• STEP 1 REGISTRATION: Participants must not have been previously diagnosed with a medical condition that makes them ineligible for immune based combination therapy or nephrectomy
• STEP 2 REGISTRATION: Participants must not show progression in the primary tumor. Participants who are considered to have pseudo progression are allowed
• STEP 2 REGISTRATION: Participants must not have known active brain metastases. Participants with previously treated brain metastases are eligible if participant has no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies are not required. If brain imaging studies are performed, they must be negative for disease
• STEP 2 REGISTRATION: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for two years
Procedure: Cytoreductive Nephrectomy, Drug: Active Comparator
Metastatic Renal Cell Carcinoma, Metastatic Clear Cell Renal Cell Carcinoma, Stage IV Renal Cell Cancer AJCC v8, Kidney
UT Southwestern
EA2176: Phase 3 Clinical Trial of Carboplatin and Paclitaxel +/- Nivolumab in Metastatic Anal Cancer Patients
This phase 3 trial compares the addition of nivolumab to chemotherapy (carboplatin and paclitaxel) versus usual treatment (chemotherapy alone) for the treatment of anal cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as carboplatin and paclitaxel, 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. Giving nivolumab together with carboplatin and paclitaxel may help doctors find out if the treatment is better or the same as the usual approach.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
177531
ALL
18 Years and over
PHASE3
NCT04444921
STU-2021-0016
Inclusion Criteria:
* Patient must have inoperable, recurrent, or metastatic disease not amenable to curative therapy
* Patient must have histological or cytological confirmation of anal squamous cell carcinoma (includes basaloid and cloacogenic lesions) from the primary tumor or a newly diagnosed recurrent/metastatic lesion
* Patient must be \>= 18 years of age
* Patient must have Eastern Cooperative Oncology Group (ECOG) performance status =\< 0-1
* Patients must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 and based on radiologic assessment performed \< 4 weeks prior to randomization
* Patient receiving palliative (limited-field) radiation therapy is allowed, as long as the lesion treated for palliation is not a target lesion and is \> 7 days from completion from palliative radiation
* Patients with brain metastasis are eligible if patient is asymptomatic and if treatment ended \> 3 months prior to randomization. Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression within 4 weeks prior to randomization
* Absolute neutrophil count \>= 1,500/mcL (obtained \< 14 days prior to randomization)
* Platelets \>= 100,000/mcL (obtained \< 14 days prior to randomization)
* Hemoglobin (Hb) \>= 9 g/dL for males and \>= 9 g/dL for females (obtained \< 14 days prior to randomization)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (obtained \< 14 days prior to randomization)
* Aspartate transaminase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\]) /alanine transferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 x institutional ULN (obtained \< 14 days prior to randomization)
* Creatinine =\< 1.5 x institutional ULN OR creatinine clearance (CrCl) \>= 50 mL/min (if using the Cockcroft-Gault formula) (obtained \< 14 days prior to randomization)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy (ART) with CD4 count \>= 200 or have a CD4 count \< 200 but an undetectable viral load are eligible
* All HIV+ patients should be under the care of an infectious diseases specialist. If a relationship with an infectious diseases specialist is not established, an infectious disease specialist should be consulted. Records of all viral counts and peripheral T-cell counts should be documented in order to follow these values over the course of treatment
* All patients must be willing to undergo testing for HIV testing if not tested within the past 12 months
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable or on suppressive therapy (if indicated)
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with known history or current symptoms of cardiac disease, 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. Patients with a history of congestive heart failure (CHF) or who are at risk because of underlying cardiovascular disease or exposure to cardiotoxic drugs must be willing to undergo evaluation of cardiac function including electrocardiogram (EKG) and echocardiogram (ECHO) as clinically indicated
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
* Patients must agree to not receive live vaccines while on this study
Exclusion Criteria:
* Women must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All females of childbearing potential must have a blood test or urine study with a minimum sensitivity of 25 IU/L or equivalent units of Bacille Calmette-Guerin (BCG), within 14 days prior to randomization to rule out pregnancy. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) 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 not expect to conceive or father children by using accepted and effective method(s) of contraception or to abstain from sexual intercourse for at least one week prior to the start of treatment, and continue for 5 months after the last dose of protocol treatment for women of childbearing potential and 7 months after the last dose of protocol treatment for males who are sexually active with women of childbearing potential (WOCBP)
* Patient must not have had previous use of systemic chemotherapy or other investigational drugs for the treatment of inoperable recurrent or metastatic anal cancer (previous use of radiotherapy or chemoradiotherapy in this setting is not an exclusion criterion if: 1) non-irradiated target tumor lesions are present at randomization for the purpose of tumor response assessment or 2) in the absence of non-irradiated target tumor lesions, progression of the irradiated tumor lesions according to the RECIST criteria version 1.1 is documented)
* Patient must not have current or recent (within 30 days prior to randomization) treatment with another investigational drug or participation in another investigational study
* Patient must not have had prior immunotherapy
* Patient must not have a history of known hypersensitivity reaction to any platinum or taxane-based chemotherapy or monoclonal antibody
* Patient must not have active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including chronic prolonged systemic corticosteroids (defined as corticosteroid use of duration one month or greater). These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or anti-phospholipid syndrome. Patients with any of these are ineligible because of the risk of recurrence or exacerbation of autoimmune disease
* Patient must not have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids and adrenal replacement doses \< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \< 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted
* Patient must not have had major surgery performed =\< 28 days prior to randomization
* Patient must not have a history of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computed tomography (CT) scan
* Patient must not have a serious active infection requiring IV antibiotics at time of randomization
* Patient must not have other primary malignancy within the last 3 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer, or any other cancer from which the patient has been disease-free for at least 3 years
* Patient must not have known peripheral neuropathy \> grade 1 at the time of randomization (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible) DRUG: Carboplatin, BIOLOGICAL: Nivolumab, DRUG: Paclitaxel
Anal Canal Cloacogenic Carcinoma, Stage III Anal Cancer AJCC v8, Metastatic Anal Squamous Cell Carcinoma, Recurrent Anal Squamous Cell Carcinoma, Stage IV Anal Cancer AJCC v8, Unresectable Anal Squamous Cell Carcinoma, Anal Basaloid Squamous Cell Carcinoma
UT Southwestern; Parkland Health & Hospital System
Study of CHS-388 (Formerly Known as SRF388) in Patients With Advanced Solid Tumors
This is a Phase 1/1b, open-label, first-in-human, dose-escalation and expansion study of CHS-388, a monoclonal antibody that targets IL-27, as a monotherapy and in combination in patients with solid tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Hans Hammers
169573
ALL
18 Years and over
PHASE1
NCT04374877
STU-2020-0969
Part A and Part B Abbreviated
Inclusion Criteria:
* ≥ 18 years of age
* Locally advanced or metastatic (Stage IV) solid tumor that has progressed during or after standard therapy, and for whom no available therapies are appropriate (based on investigator judgment)
* Patients in Part B with advanced or metastatic ccRCC, HCC, or NSCLC must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* Patients with HCC in Part B must have at least 1 measurable target lesion according to modified RECIST (mRECIST)
* Patients with HCC must have unresectable disease, Barcelona Clinic Liver Cancer (BCLC1) Stage B (not eligible for transcatheter arterial chemoembolization \[TACE\]) or Stage C
* For patients in Part B with ccRCC, demonstrated progressive disease (PD) during or after the most recent treatment regimen. Prior treatment history must include progression during or after treatment with regimen(s) that have included a vascular endothelial growth factor (VEGF)-targeted agent and an immune checkpoint inhibitor. Patients who did not progress on but discontinued the VEGF-targeted agent for toxicity or intolerability are permitted.
* For patients in Part B with HCC, demonstrated PD during or after the most recent treatment regimen. Prior treatment history must include progression during or after treatment with a VEGF-targeted agent. Patients who did not progress on but discontinued the VEGF-targeted agent for toxicity or intolerability are permitted.
* For Part B patients in the tumor biopsy subsets only, must have tumor tissue that is accessible for pretreatment and on-treatment tumor biopsy in the opinion of the Investigator and be willing to undergo pretreatment and on-treatment biopsies per protocol
* Serum creatinine clearance ≥ 30 mL/min per Cockcroft-Gault formula or serum creatinine ≤ 2.0 x the upper limit of normal (ULN)
* Total bilirubin ≤ 1.5 x ULN (≤ 3 x ULN if elevated because of Gilbert's syndrome and ≤ 2 x ULN for patients with HCC or patients with known liver metastases)
* Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) \< 2.5 x ULN (\< 5 x ULN if liver metastasis or for patients with HCC)
* For patients with HCC, Child-Pugh class A or B7 with a serum albumin ≥ 2.8 g/dL (≥ 28 g/L)
* Adequate hematologic function, defined as absolute neutrophil count (ANC) ≥ 1.0 x 109/L, hemoglobin ≥ 9.0 g/dL, and platelet count ≥ 100 x 109/L. For patients with HCC, platelet count ≥ 75 x 109/L without transfusion
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Patients with NSCLC must have histologically confirmed locally advanced and/or metastatic Stage IV NSCLC
* Patients with NSCLC must have demonstrated progressive disease during or after the most recent treatment regimen
Part C Abbreviated Inclusion Criteria:
* ≥ 18 years of age
* Advanced RCC of any histology or advanced HCC previously treated with at least one systemic anticancer therapy OR histologically or cytologically confirmed metastatic or unresectable adenocarcinoma or squamous cell NSCLC
* Patients with HCC must have unresectable disease, Barcelona Clinic Liver Cancer (BCLC) Stage B (not eligible for transcatheter arterial chemoembolization) or Stage C
* At least 1 measurable lesion per RECIST 1.1
* Patients with HCC must have at least 1 measurable target lesion according to modified RECIST (mRECIST)
* ECOG performance status of 0-1
* ANC ≥1500/µL (1.5 x 109/L)
* Platelets ≥100 000/µL (≥ 100 x 109/L)
* Hemoglobin for participants with RCC: ≥9.0 g/dL; for participants with HCC: ≥8.5 g/dL
* Creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN
* Total bilirubin ≤1.5 × ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN
* AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
* International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
* For patients with HCC, Child-Pugh Class A or B7 with a serum albumin ≥ 2.8 g/dL (≥ 28 g/L)
* Willingness of male and female patients who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control for the duration of the study drug period (or beginning 14 days before the initiation of pembrolizumab for oral contraception), including 75 days after the last dose of CHS-388 or 120 days after the last dose of pembrolizumab; male patients must refrain from donating sperm during this period. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception with spermicide. Azoospermic male patients and WCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, female patients must still undergo pregnancy testing as described in this section.
Part C Abbreviated Inclusion Criteria Specific to Patients with RCC or HCC from Part A or Part B:
* Progressed on CHS-388 by RECIST 1.1
* Did not experience prior Grade ≥ 3 toxicity related to CHS-388
* Willingness to undergo pretreatment core or excisional biopsy if deemed safe and tumor is accessible, in the opinion of the Investigator
* Has received no systemic anticancer therapies between CHS-388 doses
Part C Abbreviated Inclusion Criteria specific to NSCLC Patients:
* No more than 3 prior lines of systemic therapy for unresectable or metastatic disease with prior radiologic progression on or following platinum-based chemotherapy and prior anti-PD-(L)1 therapy whether given alone or in combination
Part A and Part B Abbreviated Exclusion Criteria:
* Previously received an anti-IL-27 antibody or anti-IL-27 targeted therapy
* For patients in Part B with renal cell carcinoma (RCC), non-clear cell RCC histology
* For patients with HCC, known fibrolamellar or mixed hepatocellular cholangiocarcinoma
* History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs
* Major surgery within 4 weeks prior to Screening
* Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition including pneumonitis and/or interstitial lung disease, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study
Part C Abbreviated Exclusion Criteria:
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug
* Previously received an anti-IL 27 antibody or anti-IL 27 targeted therapy (exception to patients who received CHS-388 in Part A or Part B)
* No prior systemic therapy for unresectable or metastatic disease
* Received \> 4 prior systemic regimens for unresectable or metastatic disease (prior PD-(L)1 inhibitors are allowed if the patient did not discontinue therapy due to ≥ Grade 3 drug-related toxicity)
* For patients with HCC, fibrolamellar histology or mixed hepatocellular cholangiocarcinoma
* For patients with HCC, moderate or severe ascites
* For patients with HCC, inability to undergo disease evaluation with triphasic computed tomography or magnetic resonance imaging because of contrast allergy or other contraindication
* For patients with HCC, imaging findings consistent with ≥ 50% liver occupation by HCC tumors
* History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs
* Surgeries that required general anesthesia must be completed at least 2 weeks before first study drug administration
* Prior autologous stem cell transplant ≤ 3 months before the first dose
* Prior allogeneic hematopoietic cell transplant within 6 months of the first dose or with a history of or current clinical Graft-Versus-Host Disease
* Has had an allogenic tissue/solid organ transplant
* Other unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study
Part D Abbreviated Inclusion Criteria
* ≥ 18 years of age
* Histologically or cytologically confirmed metastatic or unresectable adenocarcinoma or squamous cell NSCLC
* No more than 3 prior lines of systemic therapy for unresectable or metastatic disease with prior radiologic progression on or following platinum-based chemotherapy and prior anti-PD-(L)1 therapy whether given alone or in combination
* At least 1 measurable lesion per RECIST 1.1
* ECOG performance status of 0-1
* ANC ≥1500/µL (1.5 x 109/L)
* Platelets ≥100 000/µL (≥ 100 x 109/L)
* Hemoglobin for participants with RCC: ≥9.0 g/dL
* Creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN
* Total bilirubin ≤1.5 × ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN
* AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
* International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
* Willingness of male and female patients who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control for the duration of the study drug period (or beginning 14 days before the initiation of pembrolizumab for oral contraception), including 75 days after the last dose of CHS-388 or 180 days after the last dose of toripalimab; male patients must refrain from donating sperm during this period. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception with spermicide. Azoospermic male patients and WCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, female patients must still undergo pregnancy testing as described in this section.
Part D Abbreviated Exclusion Criteria:
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug
* Previously received an anti-IL 27 antibody or anti-IL 27 targeted therapy (exception to patients who received CHS-388 in Part A or Part B)
* No prior systemic therapy for unresectable or metastatic disease
* Received \> 4 prior systemic regimens for unresectable or metastatic disease (prior PD-(L)1 inhibitors are allowed if the patient did not discontinue therapy due to ≥ Grade 3 drug-related toxicity)
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137), and was discontinued from that treatment due to a ≥ Grade 3 irAE.
because of contrast allergy or other contraindication
* History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs
* Surgeries that required general anesthesia must be completed at least 2 weeks before first study drug administration
* Prior autologous stem cell transplant ≤ 3 months before the first dose
* Prior allogeneic hematopoietic cell transplant within 6 months of the first dose or with a history of or current clinical Graft-Versus-Host Disease
* Has had an allogenic tissue/solid organ transplant
* Other unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study DRUG: CHS-388, DRUG: Pembrolizumab, DRUG: Toripalimab
Non-Small Cell Lung Cancer, Hepatocellular Carcinoma, Clear Cell Renal Cell Carcinoma, Advanced Solid Tumor
metastatic solid tumors, advanced solid tumors, Phase 1, CHS-388, IL-27, safety, efficacy, immunotherapy, cancer, immuno-oncology, kidney cancer, renal cell carcinoma, liver cancer, hepatocellular carcinoma, non-small cell lung cancer, pembrolizumab, PD-1, toripalimab, SRF388
UT Southwestern
Testing the Use of the Usual Chemotherapy Before and After Surgery for Removable Pancreatic Cancer
This phase III trial compares perioperative chemotherapy (given before and after surgery) versus adjuvant chemotherapy (given after surgery) for the treatment of pancreatic cancer that can be removed by surgery (removable/resectable). Chemotherapy drugs, such as fluorouracil, irinotecan, leucovorin, and oxaliplatin, 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. Giving chemotherapy before and after surgery (perioperatively) may work better in treating patients with pancreatic cancer compared to giving chemotherapy after surgery (adjuvantly).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Patricio Polanco
155689
All
18 Years and over
Phase 3
NCT04340141
STU-2020-0951
Inclusion Criteria:
PRE-REGISTRATION:
• Pathology: Histologic or cytologic proof of pancreatic adenocarcinoma or adenosquamous carcinoma
• TNM Stage: Tx-4, N0-1, M0 (M0 disease does not include spread to distant lymph nodes and organs)
• Resectable Primary Tumor: Local radiographic reading must be consistent with resectable disease defined as the following on 1) arterial and venous phase contrast-enhanced abdominal/pelvic CT scan or abdominal/pelvic magnetic resonance imaging (MRI) scan and 2) chest CT:
• No involvement or abutment of the celiac artery, common hepatic artery, superior mesenteric artery, or replaced right hepatic artery (if applicable)
• Less than 180 degree interface between tumor and vessel wall of the portal vein or superior mesenteric vein, and patent portal vein/splenic vein confluence
• No evidence of metastatic disease
• Measurable disease or non-measurable disease o Non-measurable disease is defined as cytologic or histologic confirmation of adenocarcinoma of adenosquamous carcinoma by fine needle aspiration or core-biopsy of the pancreas without measurable disease by radiographic imaging REGISTRATION:
• Confirmation of resectable disease by real-time central imaging review by the Alliance Imaging Core Lab at Imaging and Radiation Oncology Core (IROC) Ohio
• Determined to be appropriate candidate for curative-intent pancreatectomy by surgeon intending to perform the resection
• No prior radiation therapy, chemotherapy, targeted therapy, investigational therapy, or surgery for pancreatic cancer
• Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects.
• Therefore, 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
• Total Neuropathy Score < 2
• Absolute neutrophil count (ANC) >= 1,500/uL
• Platelet count >= 100,000/uL
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (If obstructive jaundice is present, then biliary drainage must be initiated and total bilirubin =< 3.0)
• Creatinine =< 1.5 x ULN OR calculated (Calc.) creatinine clearance >= 30 mL/min (Calculated using the Cockcroft-Gault equation)
• No known Gilbert's Syndrome or known homozygosity for UGAT1A1*28 polymorphism
• No comorbid conditions that would prohibit curative-intent pancreatectomy
• Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug prior to registration
• Chronic concomitant treatment with strong inducers of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inducers must discontinue the drug prior to registration
Drug: Oxaliplatin, Drug: Irinotecan Hydrochloride, Drug: Leucovorin Calcium, Drug: Fluorouracil, Procedure: Resection, Other: Questionnaire Administration
Pancreatic Cancer, Pancreas, Pancreatic Adenosquamous Carcinoma, Resectable Pancreatic Adenocarcinoma
UT Southwestern
Lower-Dose Chemoradiation in Treating Patients With Early-Stage Anal Cancer, the DECREASE Study
This phase II trial studies how well lower-dose chemotherapy plus radiation (chemoradiation) therapy works in comparison to standard-dose chemoradiation in treating patients with early-stage anal cancer. Drugs used in chemotherapy, such as mitomycin, fluorouracil, and capecitabine, 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 with radiation therapy may kill more tumor cells. This study may help doctors find out if lower-dose chemoradiation is as effective and has fewer side effects than standard-dose chemoradiation, which is the usual approach for treatment of this cancer type.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Nina Sanford
181796
ALL
18 Years and over
PHASE2
NCT04166318
STU-2020-0166
Inclusion Criteria:
* Patient must have histologically proven T1-2N0M0 invasive anal canal or anal margin squamous cell carcinoma with tumors measuring =\< 4 cm within 4 weeks prior to randomization. This may include tumors of non-keratinizing histology such as basaloid, transitional cell or cloacogenic histology. Patients with T1N0M0 anal margin squamous cell carcinoma who underwent surgical excision with negative margins are not eligible
* Patients who are human immunodeficiency virus (HIV)-negative must not have lymph nodes that are radiographically-concerning for cancer involvement using computed tomography (CT) and positron emission tomography (PET)/CT-based criteria. Measurable disease is not required
* Patients who are HIV-negative and do not have lymph nodes classified as lymph node positive, but are felt to be borderline for cancer involvement must undergo central imaging review
* NOTE: Patients requiring central imaging review will be pre-registered to Arm S. Upon central confirmation of no lymph node involvement, eligible patients may proceed to randomization on Step 1
* Patients will be considered to be lymph node (LN) positive and thereby not eligible in this study if the lymph nodes meet any of the following criteria:
* Mesorectal, presacral, internal iliac or obturator LN with:
* Short axis measuring \> 5 mm based on CT / magnetic resonance imaging (MRI) OR
* Morphologic features of irregular border or central necrosis if assessed on MRI and LN measures \> 3 mm OR
* Fludeoxyglucose F-18 (FDG) uptake \> blood pool (Deauville 3-5) based on PET/CT
* External Iliac and common Iliac:
* Short-axis measuring \> 1 cm based on CT / MRI OR
* Morphologic features of irregular border or central necrosis based on CT / MRI OR
* FDG uptake \> blood pool (Deauville 3-5) based on PET/CT
* Inguinal LN (superficial and deep) meeting any of the following criteria will be ineligible unless an FNA is performed and resulting cytology is negative.
* Morphologic features of irregular border or central necrosis based on CT / MRI
* FDG uptake \> liver (Deauville 4) based on PET/CT.
* Patients who are HIV-negative and have inguinal lymph nodes that do not meet the above criteria must undergo fine needle aspiration and have negative histology to be eligible.
* Patients who are HIV-positive must have
* A CD4 count \>= 300
* Confirmation of no lymph node involvement by central real-time review of imaging
* NOTE: Patients will be pre-registered to Arm S. Upon central confirmation of no lymph node involvement, eligible patients may proceed to randomization on Step 1
* Patient must have Eastern Cooperative Oncology Group (ECOG) - American College of Radiology Imaging Network (ACRIN) performance status of 0-2
* Patient must have no history of prior radiation or chemotherapy for this malignancy
* Patient must not have had prior potentially curative surgery (i.e. abdominal-perineal resection) for carcinoma of the anus
* Patients with excisional biopsy procedure are eligible provided there was tumor involvement of the anal canal and/or anal verge prior to resection
* Patient must not be receiving any other standard anti-cancer therapy or experimental agent concurrently with the study drugs
* Patient must not have intercurrent illness including, but not limited to, ongoing or active infection or psychiatric/social situations that, in the judgement of the investigator, would limit compliance with study requirements
* Patient must not have had significant cardiovascular disease including myocardial infarction, unstable angina, stroke, transient ischemic attack, symptomatic coronary artery disease, symptomatic congestive heart failure, or uncontrolled cardiac arrhythmia within 6 months of randomization
* Patient must not have a history of a different malignancy unless they have been disease-free for at least 2 years and are deemed by the investigator to be at low risk of recurrence
* Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ and basal cell or squamous cell carcinoma of the skin
* Patient must not have active autoimmune or connective disease
* Patients who are on anti-coagulation with warfarin within 2 weeks prior to registration and are considering the use of capecitabine, must use an alternative anti-coagulant
* NOTE: Low molecular weight heparin is permitted provided the patient's prothrombin time (PT)/international normalized ratio (INR) is \< 1.5
* Patients who will receive capecitabine and are on Dilantin for a seizure disorder must have Dilantin levels checked weekly
* Hemoglobin \> 10 g/dL (within 2 weeks prior to registration)
* Platelets \>= 100,000/mm\^3 (within 2 weeks prior to registration)
* Absolute neutrophil count \>= 1500/mm\^3 (within 2 weeks prior to registration)
* Serum creatinine must be \< 1.5 X upper limit of normal (ULN), or calculated creatinine clearance must be \> 60 ml/min (within 2 weeks prior to registration)
* Total bilirubin must be \< 2 X ULN (within 2 weeks prior to registration)
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 X institutional ULN (within 2 weeks prior to registration)
* Albumin \>= 3.0 g/dL (within 2 weeks prior to registration)
* Women must not be pregnant or breast-feeding because the study treatment administered may cause harm to an unborn fetus or breastfeeding child. 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 achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) 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 accepted and effective method(s) of contraception or to abstain from sexual intercourse for the duration of their participation in the study and for at least 6 months after the completion of treatment DRUG: Capecitabine, DRUG: Fluorouracil, RADIATION: Intensity-Modulated Radiation Therapy, DRUG: Mitomycin, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration
Anal Basaloid Carcinoma, Anal Canal Cloacogenic Carcinoma, Anal Margin Squamous Cell Carcinoma, Anal Canal Squamous Cell Carcinoma, Stage I Anal Cancer AJCC v8, Stage IIA Anal Cancer AJCC v8
UT Southwestern; Parkland Health & Hospital System
National Translational Science Network of Precision-based Immunotherapy for Primary Liver Cancer
Background: Primary Liver Cancer is the second most common cause of cancer-related death worldwide. It is the cancer with the fastest rising incidence and mortality in the United States. Researchers want to learn more about liver cancer to help them design better treatments. Objective: To better understand liver cancer. Eligibility: People ages 18 and older who have liver cancer and had or are planning to have immune therapy Design: Participants will be screened with a review of their medical records. They will be asked about their medical history and test results. Participants will come to the NIH Clinical Center. During this visit, their medical records, test results, imaging studies, and tissue samples (if available) will be gathered. Participants will learn the results of a test to see if they have any mutations known to be connected to cancer. They will learn if there are treatment options for them. Participants will give blood, urine, and stool samples or rectal swabs. Participants will not have follow-up visits just for this study. If they join another NIH research study and have visits for this other study, their medical records; test results; and blood, urine, and stool samples may be collected. This will occur about every 3 months. If they have a biopsy or surgery on another study or as part of treatment and there is leftover tissue, researchers would like to collect some of that tissue. Participants will be contacted every 6 months by phone or e-mail. They will be asked about their health. They will provide any medical records, test results, and imaging studies. Participants will be followed on this study for life.
Yujin Hoshida yujin.hoshida@utsouthwestern.edu
ALL
18 Years and over
NCT04145141
* INCLUSION CRITERIA:
* Patients with histologically/ultrasound/imaging confirmed or suspicious lesions of HCC or CCA.
* Patients with planned or a history of at least 1 dose of immunotherapy for HCC or CCA.
* Ability of subject to understand and the willingness to sign a written informed consent document.
* Age greater than or equal to 18 years old at date of study consent.
EXCLUSION CRITERIA:
• Patients with known HIV infection (as these patients may have abnormal test results which may confound the endpoints of this study)
• Patients with known HIV infection (as these patients may have abnormal test results which may confound the endpoints of this study)
Liver Cancer, Hepatocellular Carcinoma, Cholangiocarcinoma
Molecular Markers, Predictors for Response or Resistance to Immunotherapy, Sample Collection, Genetic Analysis, Natural History
Nivolumab in Treating Patients With Autoimmune Disorders and Advanced, Metastatic, or Unresectable Cancer
This phase Ib trial studies the side effects of nivolumab and to see how well it works in treating patients with autoimmune disorders and cancer that has spread to other places in the body or cannot removed by surgery. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Hans Hammers
169573
ALL
18 Years and over
PHASE1
NCT03816345
STU-2021-0100
Inclusion Criteria:
* Patients can have either histologically confirmed malignancy that is radiologically evaluable and metastatic or unresectable, or have a malignancy for which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting. Eligible tumor types include solid tumors and malignancies in which there is known evidence of clinical activity for single agent PD-1 or PD-L1 antibodies. Nivolumab is Food and Drug Administration (FDA)-approved for the treatment of melanoma, non-small cell lung cancer (NSCLC), Merkel cell cancer, bladder cancer, renal cell carcinoma (RCC), gastric cancer, hepatocellular carcinoma (HCC), cervical cancer, head and neck cancer, Hodgkin lymphoma (HL), metastatic small cell lung cancer (SCLC), and any solid tumor with microsatellite instability (MSI)-high status confirmed. Patients with HL are eligible but must follow standard response criteria. Additional tumor types may be eligible on a case by case basis upon discussion with principal investigator (PI). Patients enrolling on the trial for adjuvant use will be restricted to those with histology for which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting including but not limited to NSCLC, melanoma, RCC, cervical cancer, and bladder cancer
* Patients who have previously received other forms of immunotherapy (high-dose \[HD\] IL-2, IFN, CTLA-4) are allowed. Patients must not have received cytokine immunotherapy for at least 4 weeks before nivolumab administration. Patients who have received prior anti-CTLA4 will be allowed and the washout period is 6 weeks
* Age \>= 18 years; children are excluded from this study but may be eligible for future pediatric phase 1 combination trials
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Karnofsky \>= 60)
* Life expectancy of greater than 12 weeks
* Leukocytes \>= 1,000/mcL
* Absolute neutrophil count \>= 500/mcL
* Platelets \>= 50,000/mcL
* Total bilirubin =\< 2 x institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 x institutional ULN or =\< 8 x institutional ULN for patients with liver metastases or an autoimmune disease that is contributing to the elevation of these values
* Creatinine ULN OR glomerular filtration rate (GFR) \>= 30 mL/min (if using the Cockcroft-Gault formula)
* Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial
* If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated
* If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load
* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate central nervous system (CNS) specific treatment is not required and is unlikely to be required for at least 4 weeks (or scheduled assessment after the first cycle of treatment), and a risk-benefit analysis (discussion) by the patient and the investigator favors participation in the clinical trial
* The effects of nivolumab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men 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. WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 5 months after the last dose of investigational product. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 24 hours prior to the start of nivolumab. Women must not be breastfeeding. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL. These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days, and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) should inform the treating physician immediately
* Ability to understand and the willingness to sign a written informed consent document
* Patients with more than one autoimmune disease are eligible. The treating physician would determine which autoimmune disease is dominant and the patient would be treated under that specific cohort
Exclusion Criteria:
* Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier have not resolved or stabilized. Palliative (limited-field) radiation therapy (RT) is permitted (2 week washout from start of treatment), if all of the following criteria are met:
* Repeat imaging demonstrates no new sites of bone metastases
* The lesion being considered for palliative radiation is not a target lesion
* Patients with prior therapy with an anti-PD-1 or anti-PD-L1
* Patients with prior allogeneic hematologic transplant
* Patients who are receiving any other anticancer investigational agents
* 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 PROCEDURE: Biospecimen Collection, BIOLOGICAL: Nivolumab
Systemic Lupus Erythematosus, Multiple Sclerosis, Rheumatoid Arthritis, Ulcerative Colitis, Dermatomyositis, Psoriasis, Crohn Disease, Psoriatic Arthritis, Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm, Inflammatory Bowel Disease, Autoimmune Disease, Sjogren Syndrome, Systemic Scleroderma
UT Southwestern
Transanastomotic Tube for Proximal Esophageal Atresia With Distal Tracheoesophageal Fistula Repair (TEF)
This trial will compare the effectiveness of two common surgical practices for Type C esophageal atresia repair: esophageal atresia (EA) with distal tracheoesophageal fistula (TEF). Infants with EA/TEF requiring surgical intervention will be recruited. Subjects will be randomized to either repair with or without transanstomotic tube (TT) during esophageal anastomosis creation. Primary outcome is symptomatic anastomotic stricture development requiring dilation within 12 months.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Maria.ValenciaBradd@UTSouthwestern.edu
Samir Pandya
177098
All
up to 6 Months old
N/A
NCT03730454
STU-2020-1118
Inclusion Criteria:
• Infants diagnosed with type C esophageal atresia: proximal esophageal atresia and distal tracheoesophageal fistula
• Primary repair of the esophageal atresia within the first six months of life
• Minimum follow up of 1 year (12 months)
Exclusion Criteria:
• Other types of esophageal atresia without esophageal anastomosis creation
• Major anomaly that influences likelihood of developing primary outcome or affects surgical treatment considerations
Device: Transanastomotic Tube (5FR), Other: No Transanastomotic Tube
Esophageal Atresia, Esophagus, Tracheoesophageal Fistula
Children’s Health
Seladelpar in Subjects With Primary Biliary Cholangitis (PBC)
An Open Label Long-Term Study to Evaluate the Safety and Tolerability of Seladelpar in Subjects with Primary Biliary Cholangitis (PBC)
Call 214-648-5005
studyfinder@utsouthwestern.edu, lakeisha.johnson@utsouthwestern.edu
Marlyn Mayo
14698
All
18 Years to 75 Years old
Phase 3
NCT03301506
STU-2021-0601
Inclusion Criteria:
• Must have given written informed consent (signed and dated)
• Participated in a PBC study with seladelpar
• Females of reproductive potential must use at least one barrier contraceptive and a second effective birth control method during the study and for at least 90 days after the last dose. Male subjects who are sexually active with female partners of reproductive potential must use barrier contraception and their female partners must use a second effective birth control method during the study and for at least 90 days after the last dose
Exclusion Criteria:
Exclusion criteria are only applicable for subjects with a seladelpar interruption greater
than 4 weeks prior to Day 1 of this study and for subjects who participated in CB8025-21838
irrespective of seladelpar interruption.
• Treatment-related adverse event (AE) leading to seladelpar discontinuation in a previous PBC study with seladelpar (MBX-8025)
• A medical condition, other than PBC, that in the investigator's opinion would preclude full participation in the study or confound its results (e.g., cancer)
• AST or ALT above 3 × the upper limit of normal (ULN)
• Total bilirubin above 2 × ULN
• MELD score ≥ 12. For subjects on anticoagulation medication, evaluation of the baseline INR, in concert with any current dose adjustments in anti-coagulant medications, will be taken into account when calculating this score. This will be done in consultation with the medical monitor.
• Evidence of advanced PBC as defined by the Rotterdam criteria: albumin below 1× the lower limit of normal (LLN) AND total bilirubin above 1 × ULN)
• eGFR ≤45 mL/min/1.73 m2 (calculated by MDRD formula)
• Auto-immune hepatitis
• Primary sclerosing cholangitis
• Known history of alpha-1-antitrypsin deficiency
• Known history of chronic viral hepatitis
• For females, pregnancy or breast-feeding
• Use of colchicine, methotrexate, azathioprine, or long-term use of systemic steroids (e.g. prednisone, prednisolone, budesonide) (>2 weeks) within 2 months prior to Screening
• Current use of fibrates or use of fibrates within 3 months prior to Screening
• Current use of obeticholic acid or use of obeticholic acid within 3 months prior to Screening
• Use of an experimental or unapproved treatment for PBC within 3 months prior to Screening
• History of malignancy diagnosed or treated, actively or within 2 years, or active evaluation for malignancy; localized treatment of squamous or non-invasive basal cell skin cancers and cervical carcinoma in-situ is allowed if appropriately treated prior to Screening
• Treatment with any other investigational therapy or medical device within 30 days or within 5 half-lives, whatever is longer, prior to Screening
• Any other condition(s) that would compromise the safety of the subject or compromise the quality of the clinical study, as judged by the Investigator
• Immunosuppressant therapies (e.g., cyclosporine, tacrolimus, anti-TNF or other immunosuppressive biologics)
• Other medications that effect liver or GI functions such as absorption of medications or the roux-en-y gastric bypass procedure may be prohibited and should be discussed with the medical monitor on a case-by-case basis
• Positive for:
• Hepatitis B, defined as the presence of hepatitis B surface antigen
• Hepatitis C, defined as the presence of hepatitis C virus ribonucleic acid (RNA)
• Human immunodeficiency virus (HIV) antibody
• Active COVID-19 infection during screening
Drug: Seladelpar 5 mg Capsule, Drug: Seladelpar 10 mg Capsule
Primary Biliary Cirrhosis, Liver
PBC, Primary Biliary Cholangitis (PBC)
UT Southwestern; Parkland Health & Hospital System
A 5-year Longitudinal Observational Study of Patients Undergoing Therapy for Inflammatory Bowel Disease (TARGET-IBD)
TARGET-IBD is a 5-year, longitudinal, observational study of adult and pediatric patients (age 2 and above) being managed for Inflammatory Bowel Disease (IBD) in usual clinical practice. TARGET-IBD will create a research registry of patients with IBD within academic and community real-world practices in order to assess the safety and effectiveness of current and future therapies.
studyfinder@utsouthwestern.edu
ALL
2 Years and over
NCT03251118
Inclusion Criteria:
• Adults and children (age 2 or older) with a diagnosis of Crohn's disease (CD), Ulcerative colitis (UC), or Indeterminate colitis (IBDU) having been prescribed any IBD treatment (initial or subsequent) outside of a clinical trial.
• Have plans for future visits at the site for continued management of IBD.
Exclusion Criteria:
• Inability to provide written informed consent/assent.
• Being enrolled in any interventional study or trial for IBD treatment. Note: Patient may be enrolled in other registries or studies where IBD treatment outcomes are observed and/or reported (such as center-based registries).
• Prior total abdominal colectomy for UC or IBDU.
Ulcerative Colitis, Crohn's Disease, Indeterminate Colitis, Inflammatory Bowel Diseases
Crohn's Disease, Ulcerative colitis, Indeterminate colitis, Digestive System Diseases
Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
This phase II Pediatric MATCH trial studies how well ensartinib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with ALK or ROS1 genomic alterations that have come back (recurrent) or does not respond to treatment (refractory) and may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Ensartinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Call 214-648-5005
studyfinder@utsouthwestern.edu
ALL
12 Months to 21 Years old
PHASE2
NCT03213652
Inclusion Criteria:
* Patient must have enrolled onto APEC1621SC//NCI-2017-01251 and must have been given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621F/NCI-2017-01243 based on the presence of an actionable mutation as defined in APEC1621SC/ NCI-2017-01251
* Patients must be \>= than 12 months and =\< 21 years of age at the time of study enrollment.
* Patients must have a body surface area \>= 0.5 m\^2 at enrollment
* Patients must have radiographically measurable disease at the time of study enrollment. Patients with neuroblastoma who do not have measurable disease but have iobenguane (MIBG) positive (+) evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on a standard MRI or CT
* Note: The following do not qualify as measurable disease:
* Malignant fluid collections (e.g., ascites, pleural effusions)
* Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
* Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography \[PET\] scans) except as noted for neuroblastoma
* Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
* Previously radiated lesions that have not demonstrated clear progression post radiation
* Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age
* Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment; 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
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: \>= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
* Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil counts \[ANC\] counts): \>= 7 days after the last dose of agent
* 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
* Corticosteroids: if used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for growth factors that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
* Stem cell Infusions (with or without total body irradiation \[TBI\]):
* Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: \>= 84 days after infusion and no evidence of graft versus host disease (GVHD)
* Autologous stem cell infusion including boost infusion: \>= 42 days
* Cellular therapy: \>= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer \[NK\] cells, dendritic cells, etc.)
* Radiation therapy (XRT)/external beam irradiation including protons: \>= 14 days after local XRT; \>= 150 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial none marrow (BM) radiation
* Note: Radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
* Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): \>= 42 days after systemically administered radiopharmaceutical therapy
* Patients must not have received prior exposure to ensartinib; prior treatment with other ALK inhibitors is permitted given that at least 5 half-lives or 21 days have elapsed since therapy discontinuation, whichever is greater
* For patients with solid tumors without known bone marrow involvement:
* Peripheral absolute neutrophil count (ANC) \>= 1000/mm\^3 (within 7 days prior to enrollment)
* Platelet count \>= 100,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (within 7 days prior to enrollment)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
* 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/gender as follows (within 7 days prior to enrollment):
* Age 1 to \< 2 years: maximum serum creatinine 0.6 mg/dL for male and 0.6 mg/dL for female
* Age 2 to \< 6 years: maximum serum creatinine 0.8 mg/dL for male and 0.8 mg/dL for female
* Age 6 to \< 10 years: maximum serum creatinine 1 mg/dL for male and 1 mg/dL for female
* Age 10 to \< 13 years: maximum serum creatinine 1.2 mg/dL for male and 1.2 mg/dL for female
* Age 13 to \< 16 years: maximum serum creatinine 1.5 mg/dL for male and 1.4 mg/dL for female
* Age \>= 16 years: maximum serum creatinine 1.7 mg/dL for male and 1.4 mg/dL for female
* Bilirubin (sum of conjugated + unconjugated) =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
* Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (within 7 days prior to enrollment) (for the purpose of this study, the ULN for SGPT is 45 U/L)
* Serum albumin \>= 2 g/dL (within 7 days prior to enrollment)
* Patients must be able to swallow intact capsules
* All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
Exclusion Criteria:
* Pregnant or breast-feeding women will not be entered on this study because there is currently no available information regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study treatment and for one week after the last dose of ensartinib
* Concomitant medications
* Corticosteroids: patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Investigational drugs: patients who are currently receiving another investigational drug are not eligible
* Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible
* Anti-GVHD agents post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
* CYP3A4 agents: patients who are currently receiving drugs that are strong inducers or strong inhibitors of CYP3A4 are not eligible; strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study
* Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed
* Patients who have an uncontrolled infection are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration and Biopsy, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, DRUG: Ensartinib, OTHER: Laboratory Biomarker Analysis, PROCEDURE: Magnetic Resonance Imaging, OTHER: Pharmacological Study, PROCEDURE: Positron Emission Tomography, PROCEDURE: Radionuclide Imaging, PROCEDURE: X-Ray Imaging
Recurrent Neuroblastoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Recurrent Osteosarcoma, Recurrent Malignant Solid Neoplasm, Advanced Malignant Solid Neoplasm, Recurrent Hepatoblastoma, Recurrent Rhabdomyosarcoma, Wilms Tumor, Refractory Malignant Solid Neoplasm, Recurrent Langerhans Cell Histiocytosis, Refractory Langerhans Cell Histiocytosis, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Recurrent Medulloblastoma, Recurrent Non-Hodgkin Lymphoma, Refractory Malignant Germ Cell Tumor, Recurrent Malignant Glioma, Recurrent Rhabdoid Tumor, Recurrent Soft Tissue Sarcoma, Refractory Malignant Glioma, Refractory Medulloblastoma, Refractory Osteosarcoma, Refractory Rhabdoid Tumor, Refractory Soft Tissue Sarcoma, Recurrent Malignant Germ Cell Tumor, Refractory Ependymoma, Refractory Hepatoblastoma, Refractory Rhabdomyosarcoma, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Recurrent Ependymoma, Refractory Primary Central Nervous System Neoplasm, Recurrent Primary Central Nervous System Neoplasm, Malignant Solid Neoplasm
A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001) (LIBRETTO-001)
This is an open-label, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of selpercatinib (also known as LOXO-292) administered orally to participants with advanced solid tumors, including rearranged during transfection (RET)-fusion-positive solid tumors, medullary thyroid cancer (MTC) and other tumors with RET activation.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
206021
All
12 Years and over
Phase 1/Phase 2
NCT03157128
STU 082018-008
Key
• Participants with a locally advanced or metastatic solid tumor that:
• Has progressed on or is intolerant to standard therapy, or
• For which no standard therapy exists, or in the opinion of the Investigator, are not candidates for or would be unlikely to tolerate or derive significant clinical benefit from standard therapy, or
• Decline standard therapy
• Prior multikinase inhibitors (MKIs) with anti-RET activity are allowed
• A RET gene alteration is not required initially. Once adequate PK exposure is achieved, evidence of RET gene alteration in tumor and/or blood is required as identified through molecular assays, as performed for clinical evaluation
• Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as appropriate to tumor type
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 or Lansky Performance Score (LPS) greater than or equal to (≥) 40 percent (%) (age less than [<] 16 years) with no sudden deterioration 2 weeks prior to the first dose of study treatment
• Adequate hematologic, hepatic and renal function
• Life expectancy of at least 3 months For Phase 2: As for phase 1 with the following modifications:
• For Cohort 1: Participants must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy
• Cohorts 1 and 2:
• Enrollment will be restricted to participants with evidence of a RET gene alteration in tumor
• At least one measurable lesion as defined by RECIST 1.1 or RANO, as appropriate to tumor type and not previously irradiated
• Cohorts 3 and 4: Enrollment closed
• Cohort 5:
• Cohorts 1-4 without measurable disease
• MCT not meeting the requirements for Cohorts 3 or 4
• MTC syndrome spectrum cancers (e.g., MTC, pheochromocytoma), cancers with neuroendocrine features/differentiation, or poorly differentiated thyroid cancers with other RET alteration/activation may be allowed with prior Sponsor approval
• cfDNA positive for a RET gene alteration not known to be present in a tumor sample
• Cohort 6: Participants who otherwise are eligible for Cohorts 1, 2 or 5 who discontinued another RET inhibitor may be eligible with prior Sponsor approval
• Cohort 7: Participants with a histologically confirmed stage IB-IIIA NSCLC and a RET fusion; determined to be medically operable and tumor deemed resectable by a thoracic surgical oncologist, without prior systemic treatment for NSCLC Key Exclusion Criteria (Phase 1 and Phase 2):
• Phase 2 Cohorts 1 and 2: an additional known oncogenic driver
• Cohorts 3 and 4: Enrollment closed
• Cohorts 1, 2 and 5: prior treatment with a selective RET inhibitor Notes: Participants otherwise eligible for Cohorts 1, 2, and 5 who discontinued another selective RET inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval
• Investigational agent or anticancer therapy (including chemotherapy, biologic therapy, immunotherapy, anticancer Chinese medicine or other anticancer herbal remedy) within 5 half-lives or 2 weeks (whichever is shorter) prior to planned start of LOXO-292 (selpercatinib). In addition, no concurrent investigational anti-cancer therapy is permitted Note: Potential exception for this exclusion criterion will require a valid scientific justification and approval from the Sponsor
• Major surgery (excluding placement of vascular access) within 2 weeks prior to planned start of LOXO-292 (selpercatinib)
• Radiotherapy with a limited field of radiation for palliation within 1 week of planned start of LOXO-292 (selpercatinib), with the exception of participants receiving radiation to more than 30% of the bone marrow or with a wide field of radiation, which must be completed at least 4 weeks prior to the first dose of study treatment
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy
• Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression. Participants are eligible if neurological symptoms and CNS imaging are stable and steroid dose is stable for 14 days prior to the first dose of LOXO-292 (selpercatinib) and no CNS surgery or radiation has been performed for 28 days, 14 days if stereotactic radiosurgery (SRS)
• Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292 (selpercatinib) or prolongation of the QT interval corrected (QTcF) greater than (>) 470 milliseconds (msec)
• Participants with implanted pacemakers may enter the study without meeting QTc criteria due to nonevaluable measurement if it is possible to monitor for QT changes.
• Participants with bundle branch block may be considered for study entry if QTc is appropriate by a formula other than Fridericia's and if it is possible to monitor for QT changes.
• Required treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and certain prohibited concomitant medications
• Phase 2 Cohort 7 (neoadjuvant treatment): Participant must not have received prior systemic therapy for NSCLC.
Inclusion Criteria:
For Phase 1:
• Participants with a locally advanced or metastatic solid tumor that:
• Has progressed on or is intolerant to standard therapy, or
• For which no standard therapy exists, or in the opinion of the Investigator, are not candidates for or would be unlikely to tolerate or derive significant clinical benefit from standard therapy, or
• Decline standard therapy
• Prior multikinase inhibitors (MKIs) with anti-RET activity are allowed
• A RET gene alteration is not required initially. Once adequate PK exposure is achieved, evidence of RET gene alteration in tumor and/or blood is required as identified through molecular assays, as performed for clinical evaluation
• Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as appropriate to tumor type
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 or Lansky Performance Score (LPS) greater than or equal to (≥) 40 percent (%) (age less than [<] 16 years) with no sudden deterioration 2 weeks prior to the first dose of study treatment
• Adequate hematologic, hepatic and renal function
• Life expectancy of at least 3 months For Phase 2: As for phase 1 with the following modifications:
• For Cohort 1: Participants must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy
• Cohorts 1 and 2:
• Enrollment will be restricted to participants with evidence of a RET gene alteration in tumor
• At least one measurable lesion as defined by RECIST 1.1 or RANO, as appropriate to tumor type and not previously irradiated
• Cohorts 3 and 4: Enrollment closed
• Cohort 5:
• Cohorts 1-4 without measurable disease
• MCT not meeting the requirements for Cohorts 3 or 4
• MTC syndrome spectrum cancers (e.g., MTC, pheochromocytoma), cancers with neuroendocrine features/differentiation, or poorly differentiated thyroid cancers with other RET alteration/activation may be allowed with prior Sponsor approval
• cfDNA positive for a RET gene alteration not known to be present in a tumor sample
• Cohort 6: Participants who otherwise are eligible for Cohorts 1, 2 or 5 who discontinued another RET inhibitor may be eligible with prior Sponsor approval
• Cohort 7: Participants with a histologically confirmed stage IB-IIIA NSCLC and a RET fusion; determined to be medically operable and tumor deemed resectable by a thoracic surgical oncologist, without prior systemic treatment for NSCLC Key Exclusion Criteria (Phase 1 and Phase 2):
• Phase 2 Cohorts 1 and 2: an additional known oncogenic driver
• Cohorts 3 and 4: Enrollment closed
• Cohorts 1, 2 and 5: prior treatment with a selective RET inhibitor Notes: Participants otherwise eligible for Cohorts 1, 2, and 5 who discontinued another selective RET inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval
• Investigational agent or anticancer therapy (including chemotherapy, biologic therapy, immunotherapy, anticancer Chinese medicine or other anticancer herbal remedy) within 5 half-lives or 2 weeks (whichever is shorter) prior to planned start of LOXO-292 (selpercatinib). In addition, no concurrent investigational anti-cancer therapy is permitted Note: Potential exception for this exclusion criterion will require a valid scientific justification and approval from the Sponsor
• Major surgery (excluding placement of vascular access) within 2 weeks prior to planned start of LOXO-292 (selpercatinib)
• Radiotherapy with a limited field of radiation for palliation within 1 week of planned start of LOXO-292 (selpercatinib), with the exception of participants receiving radiation to more than 30% of the bone marrow or with a wide field of radiation, which must be completed at least 4 weeks prior to the first dose of study treatment
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy
• Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression. Participants are eligible if neurological symptoms and CNS imaging are stable and steroid dose is stable for 14 days prior to the first dose of LOXO-292 (selpercatinib) and no CNS surgery or radiation has been performed for 28 days, 14 days if stereotactic radiosurgery (SRS)
• Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292 (selpercatinib) or prolongation of the QT interval corrected (QTcF) greater than (>) 470 milliseconds (msec)
• Participants with implanted pacemakers may enter the study without meeting QTc criteria due to nonevaluable measurement if it is possible to monitor for QT changes.
• Participants with bundle branch block may be considered for study entry if QTc is appropriate by a formula other than Fridericia's and if it is possible to monitor for QT changes.
• Required treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and certain prohibited concomitant medications
• Phase 2 Cohort 7 (neoadjuvant treatment): Participant must not have received prior systemic therapy for NSCLC.
Drug: LOXO-292
Lymphoma, Non-Small Cell Lung Cancer, Colon Cancer, Medullary Thyroid Cancer, Any Solid Tumor, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Stomach, Thyroid, Urinary Bladder, Hodgkins Lymphoma, Small Intestine, Soft Tissue
LOXO-292, KIF5B-RET, M918T, CCDC6-RET, RET-PTC1, NCOA4-RET, RET-PTC, RET-PTC3, RET-PTC4, PRKAR1A-RET, RET-PTC2, GOLGA5-RET, RET-PTC5, ERC1-RET, KTN1-RET, RET-PTC8, HOOK3-RET, PCM1-RET, TRIM24-RET, RET-PTC6, TRIM27-RET, TRIM33-RET, RET-PTC7, AKAP13-RET, FKBP15-RET, SPECC1L-RET, TBL1XR1-RET, BCR-RET, FGRF1OP-RET, RFG8-RET, RET-PTC9, ACBD5-RET, MYH13-RET, CUX1-RET, KIAA1468-RET, FRMD4A-RET, SQSTM1-RET, AFAP1L2-RET, PPFIBP2-RET, EML4-RET, PARD3-RET, G533C, C609F, C609G, C609R, C609S, C609Y, C611F, C611G, C611S, C611Y, C611W, C618F, C618R, C618S, C620F, C620R, C620S, C630R, C630Y, D631Y, C634F, C634G, C634R, C634S, C634W, C634Y, K666E, E768D, L790F, V804L, V804M, A883F, S891A, R912P, CLIP1-RET, Y806C, RET fusion, RET alteration, RET mutation, RET rearrangement, RET translocation, Neoplasms by Site, Neoplasms, Non-Small Cell Lung Cancer, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Cancer of Lung, Cancer of the Lung, Lung Cancer, Neoplasms, Lung, Neoplasms, Pulmonary, Pulmonary Cancer, Pulmonary Neoplasms, Respiratory Tract Neoplasms, Lung Diseases, Respiratory Tract Diseases, Carcinoma, Bronchogenic, Bronchial Neoplasms, Medullary Thyroid Cancer, Papillary Thyroid Cancer, Thyroid Diseases, Thyroid Neoplasms, Cancer of the Thyroid, Cancer of Thyroid, Neoplasms, Thyroid, Thyroid Ademona, Thyroid Cancer, Thyroid Carcinoma, Endocrine System Diseases, Endocrine Gland Neoplasms, Head and Neck Neoplasms, Thoracic Neoplasms, CNS tumor, Primary CNS tumor, Cancer of Colon, Cancer of the Colon, Colon Cancer, Colon Neoplasms, Colonic Cancer, Neoplasms, Colonic, Malignant tumor of Breast, Mammary Cancer, Mammary Carcinoma, Human, Mammary Neoplasm, Human, Neoplasms, Breast, Tumors, Breast, Human Mammary Carcinoma, Malignant Neoplasm of Breast, Breast Carcinoma, Breast Tumors, Cancer of the Breast, Breast Neoplasms, Breast Cancer, RET Inhibitor, MTC, NSCLC, selpercatinib, neo-adjuvant treatment in early stage NSCLC
UT Southwestern
Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
This Pediatric MATCH screening and multi-sub-study phase II trial studies how well treatment that is directed by genetic testing works in pediatric patients with solid tumors, non-Hodgkin lymphomas, or histiocytic disorders that have progressed following at least one line of standard systemic therapy and/or for which no standard treatment exists that has been shown to prolong survival. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic changes or abnormalities (mutations) may benefit more from treatment which targets their tumor's particular genetic mutation, and may help doctors plan better treatment for patients with solid tumors or non-Hodgkin lymphomas.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Avanthi Shah
74989
ALL
12 Months to 21 Years old
PHASE2
NCT03155620
STU 072017-080
Inclusion Criteria:
* ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must be \>= 12 months and =\< 21 years of age at the time of study enrollment
* ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients with recurrent or refractory solid tumors, including non-Hodgkin lymphomas, histiocytoses (e.g. langerhans cell histiocytosis \[LCH\], juvenile xanthogranuloma \[JXG\], histiocytic sarcoma), and central nervous system (CNS) tumors are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG); in cases where patient enrolls prior to histologic confirmation of recurrent disease, patient is ineligible and should be withdrawn from study if histology fails to confirm recurrence; please note: Patients with Hodgkin lymphoma and plexiform neurofibroma are not eligible
* ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor Testing Requirement: Tumor sample availability requirement for stage 1 of Pediatric MATCH (patients enrolled from start of study in July 2017 through 12/31/21); Patients must have an formalin-fixed paraffin-embedded (FFPE) tumor sample available for MATCH study testing from a biopsy or surgery that was performed at any point after initial tumor recurrence/progression, or be planned to have a procedure to obtain such a sample that is considered to be of potential benefit by the treating clinicians; a tumor sample from a clinically performed diagnostic (pre-treatment) biopsy will be acceptable for enrollment onto Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse intrinsic pontine gliomas) or thalamus
* Please note: Samples that have been decalcified using standardly utilized acid-based decalcification methods are not generally suitable for MATCH study testing; the nucleic acids will have been degraded in the decalcification process
* ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor molecular profiling report availability requirement for Stage 2 of Pediatric MATCH (patients enrolled starting 2022): In stage 2 of the study, no tumor samples will be submitted for centralized clinical tumor profiling; instead, a tumor molecular profiling report from a College of American Pathologists (CAP)/ Clinical Laboratory Improvements Amendments (CLIA)-approved testing laboratory must be submitted for review by the Molecular Review Committee (MRC)
* This molecular profiling must have been performed on a tumor sample that was obtained at any point after initial tumor recurrence/progression and must be accompanied by a pathology report for the same tumor specimen; a molecular profiling report for a diagnostic (pre-treatment) tumor sample will be acceptable for enrollment onto Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse intrinsic pontine gliomas) or thalamus. In the event that molecular profiling reports are available from multiple timepoints, the most recent report should be prioritized for study submission
* ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age); note: neurologic deficits in patients with central nervous system (CNS) tumors must have been stable for at least 7 days prior to study enrollment; 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
* ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must have radiographically measurable disease; measurable disease based on imaging obtained less than or equal to 56 days prior to enrollment; patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance imaging (MRI) or computed tomography (CT)
* Note: The following do not qualify as measurable disease:
* Malignant fluid collections (e.g., ascites, pleural effusions)
* Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
* Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography \[PET\] scans) except as noted for neuroblastoma
* Elevated tumor markers in plasma or CSF
* Previously radiated lesions that have not demonstrated clear progression post radiation
* Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: NOTE: patient does not need to meet all subprotocol criteria at time of enrollment onto the APEC1621SC screening protocol, but will need to meet all criteria prior to enrollment on any assigned treatment subprotocol. Patients must be enrolled onto a subprotocol within 2 weeks (14 days) of treatment assignment
* GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age); Note: neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment; 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
* GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of treatment with subprotocol specified therapy, the patients must have radiographically measurable disease; patients with neuroblastoma who do not have measurable disease but have MIBG+ evaluable are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard MRI or CT
* Note: The following do not qualify as measurable disease:
* Malignant fluid collections (e.g., ascites, pleural effusions)
* Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
* Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography \[PET\] scans) except as noted for neuroblastoma
* Elevated tumor markers in plasma or CSF
* Previously radiated lesions that have not demonstrated clear progression post radiation
* Leptomeningeal lesions that do not meet the measurement requirements for RECIST 1.1
* GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of enrollment onto a subprotocol, the following general criteria for initiation of therapy will be required:
* Patients must have fully recovered from the acute toxic effects of all prior anticancer therapy and must meet the following minimum duration from prior anticancer directed therapy prior to enrollment to the subprotocol; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
* Cytotoxic chemotherapy or other anticancer 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 \>= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
* Anticancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil counts \[ANC\]): \>= 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
* 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
* Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
* Stem cell infusions (with or without total-body irradiation \[TBI\]):
* Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: \>= 84 days after infusion and no evidence of graft versus host disease (GVHD)
* Autologous stem cell infusion including boost infusion: \>= 42 days
* Cellular therapy: \>= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer (NK) cells, dendritic cells, etc.)
* X-ray therapy (XRT)/External Beam Irradiation including Protons: \>= 14 days after local XRT; \>= 150 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow (BM) radiation; note: radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
* Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): \>= 42 days after systemically administered radiopharmaceutical therapy
* GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: For patients with solid tumors without known bone marrow involvement:
* Peripheral absolute neutrophil count (ANC) \>= 1000/mm\^3
* Platelet count \>= 100,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
* GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
* GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: 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:
* Age: 1 to \< 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6
* Age: 2 to \< 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8
* Age: 6 to \< 10 years; maximum serum creatinine (mg/dL): male 1; female 1
* Age: 10 to \< 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2
* Age: 13 to \< 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4
* Age: \>= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4
* GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Bilirubin (sum of conjugated + unconjugated) =\< 1.5 x upper limit of normal (ULN) for age
* GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Serum glutamate pyruvate transaminase (SGPT) (alanine transferase \[ALT\]) =\< 135 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)
* GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients must be able to swallow intact capsules/tablets, unless otherwise specified in the subprotocol to which they are assigned
* GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Agent specific limitations on prior therapy will be included with specific treatment subprotocols
Exclusion Criteria:
* GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, or because there is currently no available information regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in females who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
* GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Concomitant medications
* Corticosteroids: at the time of consent and enrollment to regimen specific subprotocols, patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment to the subprotocol will not be eligible; if used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Investigational drugs: patients must meet criteria for prior therapy at the time of consent and enrollment to a subprotocol; other investigational agents may not be administered to patients while they are receiving study drug as part of a subprotocol
* Anticancer agents: patients must meet criteria for prior therapy at the time of consent and enrollment to a subprotocol; other investigational agents may not be administered to patients while they are receiving study drug as part of a subprotocol
* Anti-GVHD agents post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible
* GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have an uncontrolled infection are not eligible
* GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have had a prior solid organ transplant are not eligible
* GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Additional agent specific criteria will be included with specific treatment subprotocols PROCEDURE: Biopsy, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration and Biopsy, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, DRUG: Ensartinib, DRUG: Erdafitinib, OTHER: Laboratory Biomarker Analysis, DRUG: Larotrectinib Sulfate, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Mutation Carrier Screening, DRUG: Olaparib, DRUG: Palbociclib, OTHER: Pharmacological Study, PROCEDURE: Positron Emission Tomography, PROCEDURE: Radionuclide Imaging, DRUG: Samotolisib, DRUG: Selpercatinib, DRUG: Selumetinib Sulfate, DRUG: Tazemetostat, DRUG: Tipifarnib, DRUG: Ulixertinib, DRUG: Vemurafenib, PROCEDURE: X-Ray Imaging
Recurrent Childhood Rhabdomyosarcoma, Recurrent Neuroblastoma, Malignant Glioma, Recurrent Osteosarcoma, Recurrent Malignant Solid Neoplasm, Advanced Malignant Solid Neoplasm, Recurrent Ewing Sarcoma, Recurrent Hepatoblastoma, Wilms Tumor, Recurrent Glioma, Refractory Malignant Solid Neoplasm, Stage III Soft Tissue Sarcoma AJCC v7, Stage IV Soft Tissue Sarcoma AJCC v7, Histiocytic Sarcoma, Juvenile Xanthogranuloma, Recurrent Langerhans Cell Histiocytosis, Recurrent Peripheral Primitive Neuroectodermal Tumor, Refractory Langerhans Cell Histiocytosis, Refractory Neuroblastoma, Rhabdoid Tumor, Stage III Osteosarcoma AJCC v7, Stage IV Osteosarcoma AJCC v7, Stage IVA Osteosarcoma AJCC v7, Stage IVB Osteosarcoma AJCC v7, Refractory Non-Hodgkin Lymphoma, Recurrent Medulloblastoma, Recurrent Non-Hodgkin Lymphoma, Refractory Malignant Germ Cell Tumor, Langerhans Cell Histiocytosis, Recurrent Rhabdoid Tumor, Recurrent Soft Tissue Sarcoma, Refractory Medulloblastoma, Refractory Osteosarcoma, Refractory Peripheral Primitive Neuroectodermal Tumor, Refractory Rhabdoid Tumor, Recurrent Malignant Germ Cell Tumor, Ann Arbor Stage III Non-Hodgkin Lymphoma, Ann Arbor Stage IV Non-Hodgkin Lymphoma, Refractory Ewing Sarcoma, Refractory Glioma, Refractory Hepatoblastoma, Refractory Rhabdomyosarcoma, Recurrent Ependymoma, Refractory Primary Central Nervous System Neoplasm, Recurrent Primary Central Nervous System Neoplasm
Children’s Health
Combination Chemotherapy, Bevacizumab, and/or Atezolizumab in Treating Patients With Deficient DNA Mismatch Repair Metastatic Colorectal Cancer, the COMMIT Study
This phase III trial studies how well combination chemotherapy, bevacizumab, and/or atezolizumab work in treating patients with deficient deoxyribonucleic acid (DNA) mismatch repair colorectal cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Chemotherapy drugs, such as fluorouracil, oxaliplatin, and leucovorin calcium, 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. Bevacizumab may stop or slow colorectal cancer by blocking the growth of new blood vessels necessary for tumor growth. 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. Giving combination chemotherapy, bevacizumab, and atezolizumab may work better in treating patients with colorectal cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
177531
ALL
18 Years and over
PHASE3
NCT02997228
STU 072018-005
Inclusion Criteria:
* The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
* Diagnosis of metastatic adenocarcinoma of colon or rectum without previous chemotherapy or any other systemic therapy for metastatic colorectal cancer except for one cycle of FOLFOX or capecitabine and oxaliplatin (CAPOX), either with or without bevacizumab prior to enrollment. Upon enrollment, the preceding single cycle of FOLFOX or FOLFOX + bevacizumab, if the patient received one, will not count towards patients' assessments per protocol. Cycle 1 day 1 (C1D1) of atezolizumab or C1D1 of mFOLFOX6/bevacizumab + atezolizumab will correspond to the first day the patient received therapy on trial
* Tumor determined to be mismatch-repair deficient (dMMR) by Clinical Laboratory Improvement Act (CLIA)-certified immunohistochemical (IHC) assay with a panel of all four IHC markers, including MLH1, MSH2, PMS2, and MSH6; alternatively, MSI-H diagnosed by polymerase chain reaction (PCR)-based assessment of microsatellite alterations (either Bethesda markers or Pentaplex panel) or by next-generation sequencing (NGS) are eligible
* Documentation by PET/CT scan, CT scan, or MRI that the patient has measurable metastatic disease per RECIST 1.1
* No immediate need for surgical intervention for the primary tumor or palliative diversion/bypass
* Absolute neutrophil count (ANC) must be \>= 1500/mm\^3 (obtained within 28 days prior randomization)
* Platelet count must be \>= 100,000/mm\^3 (obtained within 28 days prior randomization)
* Hemoglobin must be \>= 8 g/dL (obtained within 28 days prior randomization)
* Total bilirubin must be =\< 4 x ULN (upper limit of normal) (obtained within 28 days prior randomization); and
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be =\< 3 x ULN for the lab with the following exception: for patients with documented liver metastases, AST and ALT must be =\< 5 x ULN (obtained within 28 days prior randomization)
* Calculated creatinine clearance \>= 30 mL/min (obtained within 28 days prior randomization)
* A urine sample tested for proteinuria by either the dipstick method, urinalysis (UA), or a urine protein creatinine (UPC) ratio:
* The dipstick method must indicate 0-1+ protein; if dipstick reading is \>= 2+, a 24-hour urine must be done and it must demonstrate \< 1.0 g of protein per 24 hours or a UPC ratio \< 1.0
* A urine protein creatinine (UPC) ratio must be \< 1.0; if the UPC ratio is \>= 1.0 a 24-hour urine must be done and it must demonstrate \< 1.0 g of protein per 24 hours
* Urinalysis must indicate \< 30 mg/dl. If urinalysis \>= 30 mg/dl, a 24-hour urine must be done and it must demonstrate \< 1.0 g of protein per 24 hours or a UPC ratio \< 1.0
* International normalized ratio of prothrombin time (INR) and prothrombin time (PT) must be =\< 1.5 x ULN for the lab within 28 days before randomization; patients who are therapeutically treated with an agent such as warfarin may participate if they are on a stable dose and no underlying abnormality in coagulation parameters exists per medical history, regardless of PT/INR results
* Pregnancy test done within 28 days prior randomization must be negative (for women of childbearing potential only); pregnancy testing should be performed according to institutional standards; administration of atezolizumab or mFOLFOX6/bevacizumab/atezolizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
* Women of child-bearing potential and men must agree to use adequate contraception methods that result in a failure rate of \< 1% per year during the treatment period (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 5 months (150 days) after the last dose of atezolizumab, 6 months after the last dose of bevacizumab, and 6 months after the last dose of mFOLFOX6; a woman is considered to be of childbearing potential if she is not postmenopausal, has not reached a postmenopausal state (\>= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus); examples of contraceptive methods with a failure rate of \< 1% per year include: bilateral tubal ligation; male partner sterilization; intrauterine devices; the reliability of sexual abstinence should be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception; men must refrain from donating sperm during this same period
Exclusion Criteria:
* Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies, fluoropyrimidines, folic acid derivatives or oxaliplatin
* Uncontrolled high blood pressure defined as systolic blood pressure (BP) \> 150 mmHg or diastolic BP \> 100 mmHg with or without anti-hypertensive medication; patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria
* Documented New York Heart Association (NYHA) class III or IV congestive heart failure
* Serious or non-healing wound, skin ulcer, or bone fracture
* History of inherited bleeding diathesis, gastrointestinal (GI) perforation, significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis or symptomatic peripheral ischemia, transient ischemic attack \[TIA\], cerebrovascular accident \[CVA\] or arterial thrombotic event), abdominal fistula, intra-abdominal abscess, or active GI bleeding (with cause not addressed) within 6 months prior to randomization, or other medical condition in the opinion of the treating oncologist that makes the risk of cardiovascular or bleeding complications with bevacizumab use unacceptably high
* Other malignancies are excluded unless the patient has completed therapy for the malignancy \>= 12 months prior to randomization and is considered disease-free; patients with the following cancers are eligible if diagnosed and treated within the past 12 months: in situ carcinomas or basal cell and squamous cell carcinoma of the skin
* Known DPD (dihydro pyrimidine dehydrogenase) deficiency
* Symptomatic peripheral sensory neuropathy \>= grade 2 (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 5.0)
* Prior treatment with oxaliplatin chemotherapy within 6 months prior to randomization
* History of grade 2 hemoptysis (defined as 2.5 mL of bright red blood per episode) within 1 month prior to screening
* Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents; patients who have received prior treatment with anti-CTLA-4 may be enrolled provided the following requirements are met:
* Minimum of 12 weeks from the first dose of anti-CTLA-4 and \> 6 weeks from the last dose to randomization
* No history of severe immune-related adverse effects (CTCAE grade 3 and 4) from anti-CTLA-4
* Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 14 days prior to randomization; however,
* Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea; or chronic daily treatment with corticosteroids with a dose of =\< 10 mg/day methylprednisolone equivalent) may be enrolled
* The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
* Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease; however,
* 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 if polymerase chain reaction (PCR) for hepatits B virus (HBV) ribonucleic acid (RNA) is negative per local guidelines
* Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA per local guidelines
* 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, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis; however,
* Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible
* Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be 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%, fluocinolone 0.01%, desonide 0.05%, alclometasone 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)
* History of idiopathic pulmonary fibrosis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or active or recently active (within 90 days of randomization) pneumonitis (including drug induced) that required systemic immunosuppressive therapy (i.e. corticosteroids, etc.). History of radiation pneumonitis in the radiation field (fibrosis) is permitted
* History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
* Patients with known active tuberculosis (TB) are excluded
* Severe infections within 28 days prior to randomization, including but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
* Signs or symptoms of infection within 14 days prior to randomization
* Received oral or intravenous (IV) antibiotics within 14 days prior to randomization; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization or anticipation of need for a major surgical procedure during the course of the study
* The administration of a live, attenuated vaccine within 28 days prior to randomization
* Pregnant women are excluded from this study because atezolizumab is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with atezolizumab, breastfeeding should be discontinued if the mother is treated with atezolizumab; these potential risks may also apply to other agents used in this study; (Note: pregnancy testing should be performed within 28 days prior to randomization according to institutional standards for women of childbearing potential)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation DRUG: Atezolizumab, BIOLOGICAL: Bevacizumab, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, DRUG: Fluorouracil, DRUG: Leucovorin, PROCEDURE: Magnetic Resonance Imaging, DRUG: Oxaliplatin, PROCEDURE: Positron Emission Tomography, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration
Stage IV Colorectal Cancer AJCC v7, Metastatic Colorectal Adenocarcinoma
UT Southwestern; Parkland Health & Hospital System