StudyFinder
Search Results Within Category "Digestive Systems & Liver Disease"
35 Study Matches
A Study to Evaluate the Effectiveness and Safety of Setidegrasib, Given With Either mFOLFIRINOX or NALIRIFOX Chemotherapies, in People With Pancreatic Cancer
Pancreatic cancer is difficult to diagnose early. By the time people have been diagnosed, the cancer has usually spread to other parts of the body (metastatic). The standard treatment is chemotherapy, but other treatments are needed to improve outcomes in people with pancreatic cancer. The first treatment that people usually receive is chemotherapy. At the time this study started, some of the main standard chemotherapies for pancreatic cancer were mFOLFIRINOX or NALIRIFOX. Genes give your body instructions on how to make proteins. Proteins are needed to keep the body working properly. Many types of cancer are caused by changes in certain genes, making them faulty. Many people with pancreatic cancer have a faulty KRAS gene. One such change in the KRAS gene is called a G12D mutation. Researchers are looking for ways to stop the actions of abnormal proteins made from the KRAS G12D mutation. This study is about setidegrasib given with chemotherapy in people with pancreatic cancer who have the KRAS G12D mutation. Before setidegrasib can become an approved treatment, clinical studies need to be completed to understand how it works and how safe it is. The main aim is to learn if people who are given setidegrasib with chemotherapy live for longer than people who are given placebo with chemotherapy. Other aims are to learn if setidegrasib delays the cancer and symptoms returning, how the body processes setidegrasib, and its safety, when given with chemotherapy. People in this study will be adults with metastatic pancreatic cancer with the G12D mutation in their KRAS gene. Surgery or radiotherapy will not be an option to cure their cancer. People cannot take part if the cancer cells have spread to the thin tissue covering the brain and spinal cord (leptomeningeal disease), have symptoms of cancer in the brain or nervous system, or have recently had some other cancers that required treatment. In this study, people are given either setidegrasib with mFOLFIRINOX or NALIRIFOX chemotherapy, or a placebo with mFOLFIRINOX or NALIRIFOX chemotherapy. Whether people receive setidegrasib or placebo is decided by chance. The study doctor decides which chemotherapy (mFOLFIRINOX or NALIRIFOX) people receive. People will only receive NALIRIFOX chemotherapy (with setidegrasib or placebo) after the safety of setidegrasib with NALIRIFOX chemotherapy has been confirmed in another ongoing setidegrasib study. All of the study treatments are given slowly through a tube into a vein (infusion). People will continue to receive study treatment until their cancer gets worse, they can't tolerate the study treatment, they start other cancer treatment, they or the doctor decides the person should stop receiving study treatment, or sadly they pass away. There will be safety checks at each visit, and the doctors will continue to check for medical problems and people's wellbeing throughout the study.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
ALL
18 Years to old
PHASE3
NCT07409272
STU20260137
Inclusion Criteria:
* Participant has histologically confirmed metastatic pancreatic ductal adenocarcinoma (PDAC) with documented Kirsten rat sarcoma viral oncogene homolog (KRAS) G12D mutation based on local or central testing (confirmation of a participant's positive KRAS G12D mutation result must be available prior to randomization).
* Participant has no option for surgical resection or radiotherapy with curative intent.
* Participant consents to and provides a baseline tumor tissue specimen for the study during screening. The sample must meet the requirements described in the laboratory manual and the tumor sample guidance.
* Participant has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 within 7 days prior to randomization.
* Participant has adequate organ function as indicated by the following laboratory values within 7 days prior to randomization (if a participant has received a recent blood transfusion, the latest laboratory tests must be obtained ≥ 14 days after any blood transfusion). The laboratory values prior to the initiation of the first dose of setidegrasib/placebo (or mFOLFIRINOX/NALIRIFOX, if chemotherapy is administered during the screening period) should be used to determine eligibility. Participants who receive mFOLFIRINOX/NALIRIFOX during the screening period must meet these criteria within 7 days prior to the start of on-treatment chemotherapy (i.e., C1D1).
* Participant agrees not to participate in another interventional study while receiving study intervention in the present study (participant who is currently in the follow-up period of an interventional clinical trial is allowed).
Exclusion Criteria:
* Participant has neuroendocrine, acinar pancreatic carcinoma or pancreatic cancer with squamous/adenosquamous features.
* Participant has another prior malignancy active (i.e., requiring treatment, including hormonal therapies, or intervention) within the previous 2 years different from the primary malignancy for this study, except for local malignancies that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast, which are allowed.
* Participant has chronic inflammatory bowel disease, bowel obstruction and/or severe uncontrolled diarrhea.
* Participant has peripheral sensory neuropathy with functional impairment.
* Participant has ascites and/or pleural effusion that require invasive interventions within 30 days prior to randomization or have an indwelling drainage catheter.
* Participant has symptomatic pulmonary embolism or pulmonary embolism not being treated with anticoagulation.
* Participant has a history of interstitial lung disease or pulmonary fibrosis.
* Participant has uncontrolled seizure disorder or refractory to antiepileptics.
* Participant has known homozygous uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphism.
* Participant has had a myocardial infarction, unstable angina or coronary artery bypass surgery within 6 months prior to randomization or currently has an uncontrolled illness including but not limited to symptomatic congestive heart failure, clinically significant cardiac disease (e.g., cardiomyopathy, infiltrative cardiac disease, etc.), unstable angina pectoris, cardiac arrhythmia, obligate use of a cardiac pacemaker or long QT interval (QT) syndrome.
* Participant has received any prior systemic therapy for their metastatic PDAC (except with up to 2 doses \[i.e., 28 days; 1 cycle\] of mFOLFIRINOX or NALIRIFOX during the screening period. If a participant received \[neo\]adjuvant chemotherapy, tumor recurrence or disease progression must have occurred ≥ 6 months after completing the last dose of the \[neo\]adjuvant therapy).
* Participant has had prior treatment with a KRAS G12D-targeted agent.
* Participant has a corrected QT interval by Fridericia (QTcF) (single electrocardiogram \[ECG\]) \> 470 msec during the screening period. DRUG: Setidegrasib, DRUG: Oxaliplatin, DRUG: Leucovorin, DRUG: Irinotecan, DRUG: fluorouracil, DRUG: liposomal irinotecan, DRUG: Placebo
Pancreatic Cancer, Metastatic Pancreatic Cancer, Metastatic Pancreatic Adenocarcinoma
Pancreatic Cancer, Metastatic Pancreatic Cancer, Metastatic Pancreatic Adenocarcinoma, ASP3082, setidegrasib, KRAS G12D, PDAC, mFOLFIRINOX, NALIRIFOX
UT Southwestern
A Study to Select a Dose Regimen (Part A) and to Investigate Overall Survival (Part B) With Nanvuranlat Compared With Physician's Best Choice in Participants Aged 18 Years or Older With Biliary Tract Cancer (Beacon-BTC)
This study is designed to 1) select a dose regimen for continued development and 2) evaluate nanvuranlat versus Physicians Best Choice (PBC) (FOLFOX, FOLFIRI, or Best Supportive Care (BSC)) in participants aged 18 years and over with BTC. Participants enrolling in Part A the trial will be randomly assigned to receive 1 of 3 nanvuranlat dose regimens or PBC. In Part B, participants will be randomly assigned to receive nanvuranlat or PBC. Participants will receive treatment every 2 weeks for as long as they do not experience safety issues, or their cancer gets worse, and the study doctor feels they should stop treatment. Health measurements including physical examinations, vital signs, ECGs, and safety laboratory tests will be performed to monitor safety, and tumor imaging will be performed to monitor cancer response to treatment. Other exploratory makers will be measured to better understand how nanvuranlat works.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Hsieh
ALL
18 Years to old
PHASE3
NCT07265674
STU20252028
Inclusion Criteria:
\- Individuals are eligible to be included in the study only if all of the following criteria apply:
• At least 18 years of age inclusive at the time of signing the informed consent.
• Provides informed written consent according to local laws or regulations.
• Able and willing to comply with scheduled visits, treatment plans, procedures, and laboratory tests, including peripheral blood and urine sampling during the study.
• Willing to participate in LAT1 testing and NAT2 and transporter genotyping. Note: For LAT1 testing, if the participant does not have archival tissue and a fresh biopsy is not in the best interest of the participant, they will still be eligible for the trial.
• Cancer must be metastatic, locally advanced and unresectable, or not amenable to treatment with local therapies that could offer a reasonable likelihood of clinical benefit.
• Histologic or cytologic diagnosis of BTC.
• Has BTC that is classified as either an IHC, EHC, or GBC based on surgical, clinical, or laparoscopic findings and/or radiological imaging (eg, CT, MRI).
• Has received 1 prior appropriate platinum (cisplatin, carboplatin, or oxaliplatin)-based therapy for advanced disease (locally advanced or metastatic) with or without a mAb targeting PD-1 or PD-L1.
• Disease progression during or within 6 months of neoadjuvant or adjuvant treatment with a platinum-containing regimen will count as having received 1 prior regimen.
• If a patient has a mutation/fusion of IDH1, FGFR2 or NTRK, or an amplified, mutated, or overexpressed form of HER2, or a recognized aberration in a validated "driver" of BTC, and was treated with an appropriate targeted agent, or the patient's tumor was determined to be MSI-H and an appropriate PD-1/PD-L1 mAb was administered, the targeted therapy or immunotherapy will NOT count as a separate line of treatment.
• ECOG PS of 0 or 1.
• Expected life expectancy of at least 90 days after the first day of treatment as per the site Investigator.
• At least 1 measurable lesion by RECIST v1.1 based on imaging (eg, CT, MRI) performed within 28 days prior to initiation of study intervention. Those who have received prior local therapy, including but not limited to embolization, chemoembolization, radiation therapy, and/or other appropriate ablative procedures to a measurable lesion that is within the treatment and shown ≥ 20% growth in size since posttreatment assessment.
• Resolution to ≤ Grade 1 by the NCI CTCAE v 5.0 (or higher) of all clinically significant toxic effects of prior chemotherapy or other treatments, except for alopecia and peripheral neuropathy (these must have resolved to ≤ Grade 2). If medical therapy is required for the treatment of a laboratory abnormality, the dose and laboratory value(s) should be stable.
• Adequate hematologic function:
• ANC ≥ 1.5 × 109/L. Myeloid growth factors must not have been administered within 7 days before the participant's first dose of study intervention.
• Hemoglobin ≥ 8.5 g/dL and no RBC transfusions during the 14 days before the participant's first dose of study intervention.
• Platelet count ≥ 100 × 109/L and no platelet transfusions during the 14 days before the participant's first dose of study intervention.
• Adequate baseline organ function, as demonstrated by the following:
• eGFR ≥ 50 mL/min as estimated by CKD-EPI 2021.
• Bilirubin ≤ 2 × ULN (local institution).
• AST and ALT ≤ 5 × ULN (local institution).
• Adequate coagulation function as defined by INR ≤ 1.5 OR a PT ≤ 1.5 × ULN AND an aPTT ≤ 1.5 × ULN if not receiving anticoagulation therapy. Note: Participants may receive subtherapeutic doses of warfarin while on study to maintain patency of venous devices but not with therapeutic doses of warfarin. Participants may be treated with low-molecular weight heparin.
• Women of childbearing potential must be willing to use a highly effective method of contraception throughout the study and study follow up or for at least 9 months after the last dose of study intervention. Note: A woman is of nonchildbearing potential if she meets 1 of the following criteria: a) postmenopausal with at least 12 months of spontaneous amenorrhea; b) has had a bilateral oophorectomy; or c) has had a hysterectomy. Highly effective methods of contraception include: * Abstinence from sexual activity. * Hormonal contraception (eg, injection, implant, pill, patch, or vaginal ring as available in each country) associated with inhibition of ovulation (both estrogen and progestogen and progestogen only) in use for at least 30 days before administration of study intervention. * Intrauterine device in use for at least 30 days before administration of study intervention. * Intrauterine hormone-releasing system in use for at least 30 days before administration of study intervention. * Bilateral tubal occlusion/ligation at least 6 months before administration of study intervention. * Partner who has been vasectomized at least 6 months before administration of study intervention.
• Males and their female partners must use a highly effective method of birth control if female partner(s) is of childbearing potential, and males must not donate sperm during the study and for 9 months after the last dose of study intervention.
Exclusion Criteria:
* Individuals will be excluded from study participation if they meet any of the following criteria:
• Received systemic therapy or an investigational agent before washing out, as follows:
• \< 2 weeks prior to Cycle 1 Day 1 for systemic non-immune-based therapy
• \< 3 weeks prior to Cycle 1 Day 1 for immune-based therapy
• ≤ 5 half-lives or 3 weeks (whichever is longer) prior to Cycle 1 Day 1 for an investigational agent
• Received radiotherapy to metastatic sites within 2 weeks of Cycle 1 Day 1. Patients must have recovered from all radiation-related toxicities and not require corticosteroids. A 1 week washout is permitted for palliative radiation with a limited port ≤ 2 weeks of radiotherapy to non-CNS disease.
• Underwent hepatic radiation, chemoembolization, or radiofrequency ablation \< 4 weeks prior to Cycle 1 Day 1.
• Underwent major surgery \< 3 weeks before Screening and has not recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention.
• Known active CNS metastases and/or carcinomatous meningitis. Those with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of PD for at least 4 weeks by repeat imaging), clinically stable, and without requirement of corticosteroid treatment for at least 14 days prior to first dose of study intervention. For those with a history of CNS involvement, repeat imaging should be performed during study screening. However, CNS imaging is not required prior to study entry unless there is clinical suspicion of CNS involvement.
• Clinically significant cardiovascular disease (eg, uncontrolled or any New York Heart Association Class 3 or 4 heart failure, uncontrolled angina, history of myocardial infarction, unstable angina, or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
• Resting QTcF \> 470 msec at screening.
• An additional active malignancy that is progressing or has required active treatment within the past 3 years. Cases involving a past cancer history with substantial potential for recurrence must be discussed with the Medical Monitor before study entry. Patients with the following concomitant neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ (including transitional cell carcinoma, cervical intraepithelial neoplasia, breast cancer, and melanoma in situ), organ-confined prostate cancer with no evidence of PD.
• Require strong inhibitors of P-gp, BCRP, OATP1B1, OATP1B3, OATP1A2, and OAT3 transporters unless they can be transferred to other medications within ≥ 5 half-lives of treatment.
• Require sensitive substrates of OATP1B1 and OATP1B3 unless they can be transferred to other medications within ≥ 5 half-lives of treatment.
• Known positive status for HIV, has not been treated with established appropriate antiretroviral therapy for at least 4 weeks, and has a hydrophobic interaction chromatography viral load \< 400 copies/mL and a CD4+ T-cell (CD4+) counts ≥ 350 cells/µL prior to enrollment. No HIV testing is required unless mandated by local health authority.
• Active or chronic HBV and active (not cured) HCV. Participants who are HBV carriers without active disease (HBV DNA titer \< 1000 copies/mL or 200 IU/mL) or cured HCV (negative HCV RNA test) with confirmed viral clearance that are not receiving ongoing treatment and without residual chronic liver disease may be enrolled.
• An uncontrolled intercurrent illness including, but not limited to medical illness; uncontrolled infection requiring therapy; psychiatric illness; alcohol or drug dependence; social situations or a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator or Medical Monitor.
• Requires therapeutic doses of warfarin (ie, requires monitoring). A washout period of 7 days before administration of a participant's first dose of study intervention is required for those in whom therapeutic doses of warfarin are discontinued. Note: Warfarin at a low daily dose to maintain patency for indwelling venous catheters is allowed. Low-molecular weight heparin and direct-acting oral anticoagulants, according to the inclusion requirements pertaining to coagulation test results, are allowed.
• Clinically significant edema or intracavitary fluid collections (eg, ascites, pleural effusion, pericardial effusions) resulting in moderate symptoms and/or requiring frequent drainage.
• Previously developed shock, anaphylaxis, or renal disorder due to SBECD.
• WOCBP who is pregnant, lactating, or discontinued lactation \< 12 weeks prior to Screening, or who plans to become pregnant or initiate lactation during the study.
• Known reaction or contraindication to any component of study intervention (ie, oxaliplatin, leucovorin \[including levoleucovorin\], and 5-FU \[FOLFOX\] and irinotecan, leucovorin, and 5-FU \[FOLFIRI\]).
• Known DPD deficiency. Screening for DPD deficiency is not mandated but should be considered in subjects who have had severe toxicity due to fluoropyrimidine-based therapy in the past.
DRUG: Nanvuranlat, OTHER: Physician's Best Choice
Advanced Biliary Tract Cancer, Biliary Tract Cancer (BTC), Liver, Other Digestive Organ
Intrahepatic cholangiocarcinoma (IHC), Extrahepatic cholangiocarcinoma (EHC), Gallbladder carcinoma (GBC)
UT Southwestern
Combining Immunotherapy and Radiation Therapy to Help Patients Avoid Bladder Removal After Treatment Shrinks Muscle Invasive Bladder Cancer, BRIGHT Trial
This phase II trial tests the effect of giving pembrolizumab in combination with radiation therapy after chemotherapy in preventing surgery to remove the bladder in patients with muscle invasive bladder cancer. Standard of care therapy includes chemotherapy before surgery (neoadjuvant) to shrink or get rid of the tumor. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Photon beam radiation therapy is a type of radiation therapy that uses x-rays or gamma rays that come from a special machine called a linear accelerator. The radiation dose is delivered at the surface of the body and goes into the tumor and through the body. Giving pembrolizumab in combination with radiation therapy after neoadjuvant chemotherapy may help prevent surgical removal of the bladder in patients with muscle invasive bladder cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
ALL
18 Years to old
PHASE2
NCT07061964
STU20252024
Inclusion Criteria:
* Participants must have histologic evidence of cT2-T4aN0M0 muscle invasive urothelial carcinoma of the bladder within 180 days prior to starting neoadjuvant therapy (NAT)
* Participants must have had CT chest/abdomen/pelvis (C/A/P), MRI C/A/P or PET within 60 days prior to starting NAT to determine cT2-T4aN0M0
* Participants must have undergone TURBT with biopsy of areas of prior disease and systematic biopsies (left and right lateral, dome, posterior wall and trigone) and radiologic staging showing clinically T0-T1 disease within 60 days after the last dose of NAT. At least 4 out of 5 systematic biopsies must be performed
* NOTE: This TURBT must be within 90 days prior to registration. Registration must be within 90 days after the last dose of NAT
* Participants must have imaging of the chest, abdomen, and pelvis performed using CT or MRI preferably with contrast. Fludeoxyglucose F-18 (FDG) PET-CT can also be used for staging. If FDG PET-CT is used, then it is at the discretion of the investigator if they want to additionally obtain diagnostic CT or MRI with contrast within 60 days after the last dose of NAT
* Participants with lymph nodes ≥ 1.0 cm in the shortest cross-sectional diameter on imaging (CT or MRI of abdomen and pelvis) after completion of NAT must have a PET-CT within 70 days prior to registration. A biopsy in the setting of negative PET-CT is not required unless there is strong clinical suspicion for nodal involvement with tumor. Participants with a positive PET are deemed ineligible unless a biopsy is performed and shows no evidence of tumor involvement
* NOTE: For questions regarding the above eligibility criteria, please contact the study chairs in addition to the Southwest Oncology Group (SWOG) Statistics and Data Management Center (SDMC)
* Participants must not have evidence of ≥ T2, or N1-3, or M1 disease after NAT
* Participants must not have the presence of small cell, neuroendocrine carcinoma, plasmacytoid variants on any pathology
* Participants must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder within 24 months prior to registration except Ta/T1/carcinoma in situ (CIS) of the upper urinary tract, including renal pelvis or ureter if the participant underwent complete nephroureterectomy
* NOTE: Participants with mixed variant histology will be eligible for the trial if the majority (\> 50%) of the tumor is urothelial cell carcinoma
* Participants will be allowed to continue PD-1/L-1 inhibitor therapy received as part of standard of care neoadjuvant therapy while they undergo pre-registration assessments (TURBT and imaging)
* Participants must have received at least 3 and no more than 6 cycles of Food and Drug Administration (FDA) approved NAT for MIBC. These include cisplatin-based combination chemotherapy (e.g. cisplatin and gemcitabine \[GC\] with or without PD-1/L1 inhibitors) dose dense or accelerated methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) or enfortumab vedotin with PD-1/L1 inhibitor
* Participants must not have had anti-PD-1, anti PD-L1, anti PD-L2 or anti-CTLA4 antibody, any other antibody or drug targeting T-cell co-stimulation, enfortumab vedotin, or any other drug targeting nectin-4 other than for neoadjuvant treatment for MIBC
* NOTE: Prior intravesical immunotherapy or chemotherapy for non-muscle invasive disease is allowed
* Participants must not have had prior pelvic radiotherapy
* Participants must not have received a live attenuated vaccination within 28 days prior to registration
* Participants with conditions requiring immunosuppressive doses of steroids (\> 10 mg/day of prednisone or equivalent) or other immunosuppressive medications must not be taking steroids at time of trial registration
* Participants must be ≥ 18 years old at the time of registration
* Participants must have Zubrod performance status of 0-2
* Participants must have a complete medical history and physical exam within 28 days prior to registration
* Leukocytes ≥ 3 x 10\^3/uL (within 28 days prior to registration)
* Absolute neutrophil count ≥ 1.5 x 10\^3/uL (within 28 days prior to registration)
* Platelets ≥ 100 x 10\^3/uL (within 28 days prior to registration)
* Total bilirubin ≤ institutional upper limit of normal (ULN) unless history of Gilbert's disease (within 28 days prior to registration)
* Participants with history of Gilbert's disease must have total bilirubin ≤ 5 x institutional ULN
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x institutional ULN (within 28 days prior to registration)
* Participants must have a creatinine ≤ the institutional (I)ULN OR measured OR calculated creatinine clearance ≥ 40 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration
* Participants 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 II or better
* Participants with a history of human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration
* For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured (defined as undetectable HCV viral load)
* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
* Participants must be offered the opportunity to participate in specimen banking
* Participants who can complete the PRO-CTCAE questionnaire in English or Spanish will be offered the opportunity to participate in the optional patient-reported outcome study
* NOTE: As a 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
* 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
* For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and central institutional review board (CIRB) regulations PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, PROCEDURE: Cystoscopy, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Pembrolizumab, RADIATION: Photon Beam Radiation Therapy, PROCEDURE: Positron Emission Tomography, OTHER: Questionnaire Administration, PROCEDURE: Transurethral Resection of Bladder Tumor
Muscle Invasive Bladder Urothelial Carcinoma, Stage II Bladder Cancer AJCC v8, Stage IIIA Bladder Cancer AJCC v8, Urinary Bladder
UT Southwestern
A Study With NKT5097 for Adults With Advanced/Metastatic Solid Tumors
The goal of this open-label dose escalation and expansion study is to evaluate the safety and tolerability of NKT5097 in adults with advanced/metastatic tumors (emphasis on breast cancer and solid tumors with CCNE1 amplification). Main questions to answer include: * What is the recommended dose for expansion and/or Phase 2, for both monotherapy and in combination with ET * What medical issues/symptoms do participants experience when taking NKT5097 as monotherapy as well as in combination with ET
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Nisha Unni
ALL
18 Years to old
PHASE1
NCT07029399
STU20251544
Inclusion Criteria:
* Able to provide written informed consent
* Advanced unresectable or metastatic solid tumor (Part 1, 2 \& 3 only)
* Advanced unresectable or metastatic HR+/HER2- breast cancer (Part 4 \& 5 only)
* Refractory to or unable to tolerate existing therapies (Part 1, 2 \& 4 only)
* Measurable or evaluable disease (Part 1, 2, \& 4 only).
* Measurable disease (Part 3 \& 5 only)
* Eighteen years of age or older
* ECOG status of 0 or 1
* Adequate organ function
* Patients with female reproductive organs must be surgically sterile, post- menopausal or willing to use effective contraception per protocol
* Patients who are capable of insemination must be willing to use highly effective contraception and to refrain from sperm donation during treatment and for 28 days after the last dose
* Able to swallow oral meds
* Willing to provide tumor tissue
Exclusion Criteria:
* Advanced solid tumor that is a candidate for curative treatment
* History of another malignancy except for the following: adequately treated local basal cell or squamous carcinoma of the skin, in situ cervical cancer, adequately treated papillary noninvasive bladder cancer, other adequately treated Stage I or Stage II cancers currently in complete remission
* Not recovered from the effects of prior anticancer therapy
* Clinically significant cardiovascular event, including myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism, within 6 months
* Known active CNS metastases and/or carcinomatous meningitis
* Active interstitial lung disease requiring treatment
* History of uveitis, retinopathy, or other clinically significant retinal disease
* Major surgery within 30 days of administration of first dose
* Active uncontrolled infectious disease
* Significant liver disease (Child Pugh class B or C)
* Should not have received any prior selective investigational inhibitors or degraders (Part 5 only) DRUG: NKT5097 CDK2/CDK4 dual degrader, DRUG: Fulvestrant, DRUG: Letrozole
HR+ Breast Cancer, Triple Negative Breast Cancer (TNBC), CCNE1 Amplified Advanced Solid Tumors, HR+ HER2- Breast Cancer, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Liver, Lung/Thoracic, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Urinary, Ovary, Pancreas, Prostate, Small Intestine, Stomach, Urinary Bladder, Uterine (Endometrial)
CCNE1, cyclin E1, triple negative breast cancer, TNBC, estrogen receptor positive, HER2-, breast cancer, post CDK4/6i, HER2 expression, Fulvestrant, Letrozole, endocrine therapy, refractory, endocrine resistant, endocrine sensitivity, metastatic
UT Southwestern
A Clinical Study of Calderasib (MK-1084) With Targeted Therapy and Chemotherapy in People With Colorectal Cancer (MK-1084-012/KANDLELIT-012)
Researchers are looking for other ways to treat locally advanced or metastatic colorectal cancer (mCRC) that is unresectable and has a gene mutation called KRAS G12C. Standard (or usual) treatments for this type of colorectal cancer may include mFOLFOX6 with or without bevacizumab. Researchers want to learn if adding calderasib (the study medicine) and cetuximab to mFOLFOX6 can treat locally advanced or mCRC with the KRAS G12C mutation. Calderasib and cetuximab are targeted therapies. The goals of this study are to learn: * About the safety of calderasib with cetuximab and mFOLFOX6 and if people tolerate the treatments * If people who receive calderasib with cetuximab and mFOLFOX6 live longer without mCRC growing or spreading compared to people who receive mFOLFOX6 with or without bevacizumab.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
ALL
18 Years to old
PHASE3
NCT06997497
STU20251284
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has a histologically confirmed diagnosis of locally advanced unresectable or metastatic (unresectable Stage III or Stage IV as defined by American Joint Committee on Cancer \[AJCC\] eighth edition) colorectal adenocarcinoma
* Part 2 only: Has not received systemic anticancer therapy for locally advanced unresectable or metastatic colorectal cancer; an exception is permitted for 1-2 cycles of FOLFOX or 1 cycle of CAPOX as optional chemotherapy before or during the screening period
* Demonstrates presence of a Kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
* Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy and have undetectable HBV viral load
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, chronic diarrhea)
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
* Has known partial or complete dihydropyrimidine dehydrogenase (DPD) deficiency
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization, with the exception of the optional chemotherapy
* Has 1 or more conditions that, in the opinion of the investigator, make the participant ineligible for treatment with bevacizumab
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis or leptomeningeal disease
* Has active infection requiring systemic therapy
* Has not adequately recovered from major surgery or have ongoing surgical complications
* Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease DRUG: Calderasib, DRUG: Oxaliplatin, DRUG: Leucovorin/levofolinate calcium, DRUG: 5-Fluorouracil, BIOLOGICAL: Cetuximab, DRUG: Bevacizumab, DRUG: Bevacizumab biosimilar
Colon Adenocarcinoma, Rectal Adenocarcinoma, Colon, Rectum
UT Southwestern
A Study to Assess the Efficacy and Safety of Induction Therapy With Afimkibart (RO7790121) in Participants With Moderately to Severely Active Crohn's Disease (SIBERITE-2)
This Phase III, multicenter, double-blind, placebo-controlled study will evaluate the efficacy and safety of induction therapy with Afimkibart (also known as RO7790121) in participants with moderately to severely active Crohn's disease (CD).
Call 214-648-5005
studyfinder@utsouthwestern.edu, SOUKASEUM.OUNEPHENGSY@UTSouthwestern.edu
Moheb Boktor
ALL
16 Years to 80 Years old
PHASE3
NCT06819891
STU20250282
Inclusion Criteria:
* Confirmed diagnosis of CD
* Moderately to severely active CD
* Bodyweight \>= 40 kilogram (kg)
* Demonstrated inadequate response, loss of response and/or intolerance to at least one protocol-specified conventional or advanced CD therapy
* Males and females of childbearing potential must meet protocol criteria for contraception requirements
Exclusion Criteria:
* Current diagnosis of ulcerative colitis (UC) or indeterminate colitis, ischemic colitis, infectious colitis, radiation colitis, microscopic colitis
* Participant with a history of \>= 3 bowel resections (\> 2 missing segments of the 5 following segments: terminal ilelium, right colon, transverse colon, sigmoid and left colon, and rectum)
* Diagnosis of short gut or short bowel syndrome
* Presence of an ileostomy, colostomy or ileoanal pouch
* Participants with symptomatic bowel strictures, fulminant colitis, or toxic megacolon
* Presence of abdominal or perianal abscess
* Presence of rectovaginal, enterovaginal, high output enterocutaneous fistula, enterovesical fistulas or perianal fistulas with \>3 openings
* Participants with symptomatic bowel strictures, fulminant colitis, or toxic megacolon
* Current diagnosis or suspicion of primary sclerosing cholangitis
* Pregnancy or breastfeeding, or intention of becoming pregnant during the study
* Any past or current evidence of cancer of gastrointestinal tract, definite low-grade or high-grade colonic dysplasia
* History of non-gastrointestinal cancer, with the exception of adequately treated non-metastatic basal cell or squamous cell skin cancer or in situ cervical cancer
* Evidence of infection with Clostridioides difficile (C. difficile; formerly known as Clostridium difficile), cytomegalovirus (CMV), human immunodeficiency virus (HIV), Hepatitis B (HBV), Hepatitis C (HCV) during screening
* Has evidence of active tuberculosis (TB), latent TB not successfully treated (per local guidance) or inadequately treated TB
* Has received protocol-specified prohibited medicines, including known exposure to any type of anti-TL1A therapy DRUG: Afimkibart, DRUG: Placebo
Moderately to Severely Active Crohns Disease
UT Southwestern
Ligufalimab and Cadonilimab in Advanced Liver Cancers
The goal of this clinical trial is to find out if the combination of Ligufalimab and Cadonilimab are effective in treating advanced hepatobiliary cancers that have failed prior therapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Hsieh
ALL
18 Years to old
PHASE2
NCT06789848
STU-2024-1210
Inclusion Criteria:
• Histological confirmation of specific disease -Cohort A (HCC): Patient must have a diagnosis confirmed by histology or clinically by the American Association for the Study of Liver Diseases (AASLD) criteria in patients with cirrhosis. Known fibrolamellar HCC will be excluded. * Cohort B (BTC, biliary tract cancers): Patients must have histologically confirmed biliary tract cancer (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gall bladder cancers). Patients with combined HCC-cholangiocarcinoma may be enrolled in Cohort B.
• Locally advanced or metastatic disease * Patients with locally advanced or metastatic disease must have disease deemed not amenable to surgical and/or locoregional therapies or patients who have progressed following surgical and/or locoregional therapies. * Measurable disease, as defined as lesions that can accurately be measured in at least one dimension according to RECIST version 1.1 at least 1 cm with contrast enhanced dynamic imaging (magnetic resonance imaging or computed tomography).
• Refractory to or relapsed after prior anti-PD-1/L1 antibody therapy. May have received anti-PD-1/L1 monotherapy or combination therapy as any line of therapy including in the neoadjuvant or adjuvant setting. Patients who discontinued prior immune checkpoint inhibitor treatment due to a high-grade toxicity (Grade 4) are not eligible.
• For patients in cohort A who do not have a clinical diagnosis of HCC according to the AASLD criteria, formalin-fixed, paraffin-embedded (FFPE) tumor diagnostic tissue samples must have been obtained within 4 years from the time of consent. Baseline tissue will be requested any time after consent. It is strongly recommended that tissue is obtained from standard-of-care biopsies confirming progression of disease on prior therapy so that the patient has not received any intervening systemic anti-cancer treatment from the time that the baseline tissue was obtained.
• Prior locoregional therapy is allowed provided the following are met: 1) at least 2 weeks since prior locoregional therapy including surgical resection, chemoembolization, radiotherapy, or ablation; 2) target lesion has increased in size ≥25% since the cessation of locoregional therapy or the target lesion was not treated with locoregional therapy. Patients treated with palliative radiotherapy for symptoms will be eligible as long as the target lesion is not the treated lesion and radiotherapy will be completed at least 2 weeks prior to study drug administration.
• Age ≥ 18 years
• Child-Pugh Score A or B7 (only applicable for Cohort A)
• ECOG Performance score of 0-1
• Adequate organ and marrow function (without chronic, ongoing growth factor support or transfusion in the last 2 weeks) as defined below: -Platelet count ≥ 50,000/mm3 -Hgb ≥ 9 g/dl -Absolute neutrophil ≥ 1,000 cells/mm3 -Total bilirubin ≤ 3 mg/ml (This will not apply to subjects with Gilbert's syndrome who have persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis, or patients with hyperbilirubinemia secondary to distal malignant obstruction where endoscopic, surgical, or percutaneous bypass/stenting has been attempted. Such patients may be enrolled based in consultation with the principal investigator) -INR ≤ 2 -AST, ALT ≤ 5 times ULN * Calculated creatinine clearance (CrCl) ≥ 40 mL/min. CrCl can be calculated using the Cockroft-Gault method. * Albumin ≥ 2.0 g/dl
• All men, as well as women of child-bearing potential, defined as not surgically sterilized and between menarche and 1-year post menopause, must agree to use highly effective contraception methods (hormonal or barrier method of birth control or abstinence) 4 weeks prior to study entry, for the duration of study participation, and for 120 days after the last dose of ligufalimab or cadonilimab. 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). 11\. Women of child-bearing potential must have a negative serum pregnancy test at screening. 12\. Subjects are eligible to enroll if they have non-viral-HCC, or if they have HBV-HCC, or HCV-HCC defined as follows: 1\) HBV-HCC: Hepatitis B subjects will be allowed if they meet the following criteria: On antiviral therapy for HBV. Subjects who are anti-HBc (+), negative for HBsAg, negative for anti-HBs, and have an HBV viral load under 100 IU/mL do not require HBV anti-viral prophylaxis. 2\) HCV-HCC: Active or resolved HCV infection as evidenced by detectable HCV RNA or antibody. Patients who have failed HCV therapy as evidenced by detectable HCV RNA will be eligible. Subjects with chronic infection by HCV who are treated (successfully or treatment failure) or untreated are allowed on study. 13\. Ability to understand and the willingness to sign a written informed consent. 14\. Willing and able to comply with the requirements and restrictions in this protocol. 15\. Patients who have received the vector, protein subunit, or nucleic acid COVID-19 vaccines are eligible to enroll.
Exclusion Criteria:
• Prior liver transplant.
• Known human immunodeficiency virus (HIV) positive (testing not required).
• Use of any live vaccines against infectious diseases within 28 days of first dose of study drug administration.
• History of trauma or major surgery within 28 days prior to the first dose of study drug administration. (Tumor biopsy or placement of central venous access catheter (eg, port or similar) is not considered a major surgical procedure).
• Underlying medical conditions that, in the investigator's opinion, will make the administration of study drugs hazardous, including but not limited to: * Interstitial lung disease, including history of interstitial lung disease or non infectious pneumonitis (lymphangitic spread of cancer is not disqualifying), * Active viral, bacterial, or fungal infections requiring parenteral treatment within 14 days of the initiation of study drugs, * Clinically significant cardiovascular disease, * A condition that may obscure the interpretation of toxicity determination or AEs, * History of prior solid-organ transplantation.
• Hypersensitivity to IV contrast; not suitable for pre-medication.
• Any active autoimmune disease or a documented history of autoimmune disease or syndrome that required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for vitiligo or resolved childhood asthma/atopy. * Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. * Participants with asthma who require intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections will not be excluded from this study. Participants on chronic systemic corticosteroids will be excluded from the study.
• Known history of active bacillus tuberculosis.
• Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg/day prednisone equivalent) or other immunosuppressive medications within 14 days of study administration. Inhaled or topical steroids and adrenal replacement doses ≤10 mg/day prednisone equivalents are permitted in the absence of autoimmune disease.
• Patients who discontinued prior immune checkpoint inhibitor treatment due to Grade ≥ 3 or Grade 2 serious toxicity (i.e., pneumonitis, uveitis, neurological symptoms, cardiac toxicity, etc.) immune-related adverse events.
• Known severe hypersensitivity reactions to monoclonal antibodies (≥Grade 3).
• Prior malignancy that required systemic treatment within the previous 2 years 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 cervix, breast, or prostate cancer.
• Prisoners or subjects who are involuntarily incarcerated.
• If a participant has symptomatic or clinically active brain metastases including leptomeningeal disease, they must be excluded if: * Has evidence of progression by neurologic symptoms * Has metastatic brain lesions that require immediate intervention. * Has carcinomatous meningitis, regardless of clinical stability
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after contraception and until the termination of gestation, confirmed by a positive hCG laboratory test.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Has significant dementia or other mental condition that precludes the participant's ability to consent to the study.
• Use of other investigational drugs (drugs not marketed for any indication) within 28 days or 5 half-lives (whichever is longer) of first dose of study drugs.
• Known hypersensitivity to recombinant proteins, or any excipient contained in the study drug formulations.
DRUG: Ligufalimab, DRUG: Cadonilimab
Advanced Hepatocellular Carcinoma, Refractory Hepatocellular Carcinoma, Biliary Tract Cancer, Liver, Other Digestive Organ
liver, other digestive organs
UT Southwestern; Parkland Health & Hospital System
A Study of Amivantamab and FOLFIRI Versus Cetuximab/Bevacizumab and FOLFIRI in Participants With KRAS/NRAS and BRAF Wild-type Colorectal Cancer Who Have Previously Received Chemotherapy (OrigAMI-3)
The purpose of this study is to compare how long the participants are disease-free (progression-free survival) and and the length of time until a participant dies (overall survival), when treated with amivantamab and chemotherapy with 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride (FOLFIRI) versus either cetuximab or bevacizumab and FOLFIRI given to participants with Kirsten rat sarcoma viral oncogene/ neuroblastoma RAS viral oncogene homolog (KRAS/ NRAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type recurrent, unresectable or metastatic colorectal cancer who have previously received chemotherapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
ALL
18 Years to old
PHASE3
NCT06750094
STU20250287
Inclusion Criteria:
* Have histologically or cytologically confirmed adenocarcinoma of the colon or rectum. Participants must have recurrent, unresectable or metastatic disease
* Determined to have kirsten rat sarcoma viral oncogene/neuroblastoma RAS viral oncogene homolog (KRAS/NRAS), G12, G13 and v-raf murine sarcoma viral oncogene homolog B (BRAF) V600X (X represents any single amino acid change from the original amino acid) wild type status by local and/or central next-generation sequencing (NGS) testing
* Must agree to the submission of fresh or archival tumor tissue post progression from the most recent therapy, if clinically feasible
* Have measurable disease according to response evaluation criteria in solid tumors (RECIST) version (v) 1.1
* Have an eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1
* Participant must have received 1 line of systemic therapy (fluoropyrimidine-based and oxaliplatin-based) for metastatic colorectal cancer (mCRC), with documented radiographic disease progression on or after this line of therapy. Participants can receive anti-VEGF as prior line of therapy
Exclusion Criteria:
* Has medical history of (noninfectious) interstitial lung disease (ILD) /pneumonitis/pulmonary fibrosis or has current ILD/pneumonitis/pulmonary fibrosis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening
* Has known allergies, hypersensitivity, or intolerance to excipients of any of the following: amivantamab, cetuximab or bevacizumab or any component of FOLFIRI
* Has a prior or concurrent second malignancy other than the disease under study or one whose natural history or treatment is likely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
* Participant with known mismatch repair deficiency (dMMR)/ high microsatellite instability (MSI-H) status who has not received immunotherapy treatments
* Participant with known human epidermal growth factor receptor 2 (HER2)- positive/amplified tumor
* Has prior exposure to irinotecan, any agents that target epidermal growth factor receptor (EGFR) or mesenchymal epithelial transition (MET) BIOLOGICAL: Amivantamab, BIOLOGICAL: Cetuximab, BIOLOGICAL: Bevacizumab, DRUG: 5-fluorouracil, DRUG: Leucovorin calcium/Levoleucovorin, DRUG: Irinotecan
Colorectal Neoplasms, Colon, Rectum
UT Southwestern
PTM-101 in Pancreatic Ductal Adenocarcinoma (PDAC)
This is a multi-center, non-randomized, single-arm, open-label, phase Ib, dose escalation/dose expansion study of PTM-101 when combined with neoadjuvant chemotherapy for the treatment of treatment-naïve subjects with borderline resectable and locally advanced pancreatic ductal adenocarcinoma (PDAC).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Matthew Porembka
ALL
18 Years to old
PHASE1
NCT06673017
STU20251994
Inclusion Criteria:
* Imaging consistent with primary borderline resectable or locally advanced PDAC. PDAC may be confirmed by histology/cytology either at study-mandated laparoscopy or by prior biopsy/cytology
* Indicated for laparoscopy
* No prior therapy of any kind for PDAC
* Acceptable laboratory values
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
* Ability to provide informed consent
* No symptomatic pancreatitis
* No other active medical issues which would confound interpretation of safety monitoring, efficacy results or prevent the subject from study participation
* Subjects with childbearing potential must agree to use adequate contraception throughout study participation
Exclusion Criteria:
* Active non-pancreatic cancer that currently requires treatment or is being treated; diagnosis of another malignancy within the past 2 years. This criterion excludes a history of carcinoma in situ of the cervix, superficial non-melanoma skin cancers, or superficial bladder cancer that has been adequately treated, or stage 1 prostate cancer that does not require treatment or requires only treatment with luteinizing hormone-releasing hormone agonists or antagonists if initiated at least 30 days prior to screening). Other potentially indolent cancers may be considered.
* Contraindications or allergies to paclitaxel, PLGA (poly(lactic-co-glycolic ) acid), or contraindications to implantation of PTM-101 or chemotherapies in protocol (e.g., FOLFIRINOX, gemcitabine, nab-paclitaxel)
* Known history of human immunodeficiency virus (HIV) or active viral hepatitis
* Active ongoing infection or autoimmune disease which may preclude laparoscopy, placement of PTM-101, administration of chemotherapy or surgical resection of pancreatic tumor
* Inability to comply with activities and therapeutic interventions as outlined in the schedule of events
* Currently enrolled in another investigational drug or device trial
* Women who are pregnant or breastfeeding or who plan to become pregnant or breastfeed; men who plan to donate sperm or conceive a child
* Any other medical or surgical conditions, including prior abdominal surgery, that would preclude safe laparoscopy or implantation in the opinion of the investigator DRUG: PTM-101
Pancreatic Ductal Adenocarcinoma, Borderline Resectable Pancreatic Adenocarcinoma, Locally Advanced Pancreatic Adenocarcinoma, Pancreatic Cancer
UT Southwestern
A Study of Amivantamab and mFOLFOX6 or FOLFIRI Versus Cetuximab and mFOLFOX6 or FOLFIRI as First-line Treatment in Participants With KRAS/NRAS and BRAF Wild-type Unresectable or Metastatic Left-sided Colorectal Cancer (OrigAMI-2)
The purpose of this study is to compare how long the participants are disease-free (progression-free survival) when treated with amivantamab and chemotherapy with 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, oxaliplatin (mFOLFOX6) or 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride (FOLFIRI) versus cetuximab and mFOLFOX6 or FOLFIRI in adult participants with Kirsten rat sarcoma viral oncogene homolog (KRAS)/ Neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) wild type (WT) unresectable or metastatic left-sided colorectal cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
ALL
18 Years to old
PHASE3
NCT06662786
STU20240010
Inclusion Criteria:
* Have histologically or cytologically confirmed adenocarcinoma of the left-sided colorectal cancer. Participants must have unresectable or metastatic disease
* Determined to have Kirsten rat sarcoma viral oncogene (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type (WT) tumor by local and/or central testing (if available)
* Must agree to the submission of fresh tumor tissue
* Have measurable disease according to RECIST v1.1
* Has not received any prior systemic therapy for unresectable or metastatic colorectal cancer (CRC). Prior adjuvant/neoadjuvant therapy in the non-metastatic disease is permitted. However, the last course of adjuvant or neoadjuvant chemotherapy must have concluded greater than (\>) 12 months prior to CRC recurrence/metastases
* Have an eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1
Exclusion Criteria:
* Has medical history of (noninfectious) interstitial lung disease (ILD) /pneumonitis/pulmonary fibrosis or has current ILD/pneumonitis/pulmonary fibrosis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening
* Has known allergies, hypersensitivity, or intolerance to excipients of any of the following: (a) amivantamab or cetuximab, (b) any component of mFOLFOX6 and, (c) any component of FOLFIRI
* Has a prior or concurrent second malignancy other than the disease under study or one whose natural history or treatment is likely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
* Participant with known mismatch repair deficiency (dMMR)/ high microsatellite instability (MSI-H) status and human epidermal growth factor receptor 2 (HER2)-positive/amplified tumor
* Has prior exposure to any agents that target epidermal growth factor receptor (EGFR), mesenchymal epithelial transition (MET) or vascular endothelial growth factor (VEGF) BIOLOGICAL: Amivantamab, BIOLOGICAL: Cetuximab, DRUG: 5-fluorouracil, DRUG: Leucovorin calcium/Levoleucovorin, DRUG: Oxaliplatin, DRUG: Irinotecan Hydrochloride
Colorectal Neoplasms, Colon, Rectum
UT Southwestern
A Study With NKT3964 for Adults With Advanced/Metastatic Solid Tumors
The goal of the Dose Escalation phase of the study is to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity to determine the preliminary recommended dose for expansion (RDE) of NKT3964 in adults with advanced or metastatic solid tumors. The goal of the Expansion phase of the study is to evaluate the preliminary anti-tumor activity of NKT3964 at the RDE based on objective response rate (ORR) and determine the preliminary recommended Phase 2 dose (RP2D).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Miller
ALL
18 Years to old
PHASE1
NCT06586957
STU20252305
Inclusion Criteria:
\- Must have a pathologically confirmed advanced and unresectable or metastatic solid tumor listed below with documented disease progression on last standard treatment. Part 1 only: subjects must be refractory to, or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
Dose Escalation:
• Ovarian cancer
• Endometrial cancer (only endometrioid subtype will require CCNE1 amplification)
• Gastric, gastroesophageal junction (GEJ) or esophageal adenocarcinoma with CCNE1 amplification
• Small cell lung cancer (SCLC)
• Triple-negative breast cancer (TNBC; HER2, estrogen receptor and progesterone receptor negative)
• HR+ (includes estrogen-receptor or progesterone-receptor) and HER2- breast cancer (must have progressed following treatment with a CDK4/6 inhibitor, and is not suitable for endocrine therapy \[ET\])
• Other solid tumors with CCNE1 amplification Dose Expansion: Part 2A: HR+ and HER2- breast cancer that is locally advanced and unresectable (Stage III) or metastatic (Stage IV); previously treated with ≥1 line of standard of care (SOC) including CDK4/6 inhibitor plus ET and not suitable for further ET. Subjects must have progressed after receiving therapy for ≥3 months in the metastatic setting or for ≥6 months in the adjuvant setting. Subjects must have received ≤2 lines of systemic cytotoxic therapy (chemotherapy or cytotoxic antibody drug conjugate \[ADC\]) in the metastatic setting.. Part 2B: Advanced platinum-based-chemotherapy resistant or refractory epithelial ovarian/fallopian/primary peritoneal carcinoma or clear cell ovarian cancer (defined as recurrence ≤6 months after completing platinum-based regimen) with progression on at least one platinum containing therapy and previously treated with ≤4 prior lines of systemic therapy administered for advanced/metastatic disease and with CCNE1 amplification. Part 2C: Advanced unresectable or metastatic gastric, GEJ or esophageal adenocarcinoma with progression on at least one systemic therapy and previously treated with ≤3 prior lines of systemic therapy administered for advanced/metastatic disease, with CCNE1 amplification as determined by NGS by local liquid or tissue test. Part 2D: Advanced endometrial adenocarcinoma or uterine papillary serous carcinoma previously treated with ≤4 prior lines of systemic therapy administered for advanced/metastatic disease with CCNE1 amplification. Part 2E: Advanced/recurrent uterine carcinosarcoma previously treated with 1 prior platinum-based chemotherapy regimen and ≤3 prior lines of systemic therapy. Prior bevacizumab or PARP inhibitors are allowed and must be at least 3 weeks prior to the start of study drug. * Have adequate organ function * Subjects with female reproductive organs must be surgically sterile, post-menopausal, or must be willing to use highly effective method(s) of contraception * Ability to swallow oral medications. * Consent to provide archived tumor tissues and paired tumor biopsy at pretreatment
Exclusion Criteria:
* Locally advanced solid tumor that is a candidate for curative treatment through radical surgery and/or radiotherapy, or chemotherapy.
* History of another malignancy with exceptions
* History of lymphohistiocytic or lymphoid hyperplasia; hemophagocytic lymphohistiocytosis.
* Failed to recover from effects of prior anticancer treatment therapy to baseline or Grade ≤ 1 severity (per CTCAE)
* Clinically significant cardiovascular event within 6 months prior to start of NKT3964 treatment
* Known active CNS metastases and/or carcinomatous meningitis
* Active interstitial lung disease currently requiring treatment
* History of uveitis, retinopathy or other clinically significant retinal disease
* Active or chronic corneal disorders, other active ocular conditions requiring ongoing therapy, or any clinically significant corneal disease
* Active wound healing from major surgery within 1 month or minor surgery within 10 days before the first dose of NKT3964.
* Known human immunodeficiency virus (HIV), active hepatitis B or C infection
* Prior investigative treatment with a selective or nonselective CDK2 inhibitor or degrader
* Childs-Pugh class B or C cirrhosis or any other clinically significant liver disorder
* Palliative radiation therapy within 14 days or other radiation therapy within 4 weeks prior to C1D1 DRUG: NKT3964
Solid Tumor, Advanced Solid Tumor, Solid Tumor, Adult, Metastatic Tumor, Ovarian Cancer, Ovarian Neoplasms, Ovarian Carcinoma, Metastatic Ovarian Carcinoma, Endometrial Neoplasms, Endometrial Diseases, Metastatic Endometrial Cancer, Triple Negative Breast Cancer, Metastatic Endometrial Carcinoma, Advanced Endometrial Carcinoma, Advanced Ovarian Carcinoma, Gastric Cancer, Advanced Gastric Carcinoma, Metastatic Gastric Cancer, Metastatic Gastric Carcinoma, Small Cell Lung Cancer, Small Cell Lung Carcinoma, Triple Negative Breast Neoplasms, Platinum-resistant Ovarian Cancer, Platinum-Refractory Ovarian Carcinoma, CCNE1 Amplification, Hormone Receptor Negative Breast Carcinoma, Human Epidermal Growth Factor 2 Negative Carcinoma of Breast, Progesterone-receptor-positive Breast Cancer, Breast - Female, Breast - Male, Lung/Thoracic, Ovary
CDK 2 Inhibitor, CDK 4 Inhibitor, CDK 6 Inhibitor, CDK2 Degrader, Protein Degrader, PROTAC
UT Southwestern
A Trial to Evaluate the Safety and Activity of Fruquintinib in Minority Populations With Advanced, Previously Treated Colorectal Cancer
High blood pressure (hypertension) is a known side effect of the treatment with fruquintinib. Current research does not provide a clear answer whether minority groups such as Black/African American and/or Hispanic/Latino with refractory metastatic colorectal cancer (mCRC) have a bigger risk of higher blood pressure after treatment with fruquintinib. The main aim of this study is to learn how often adults of a minority group experience hypertension after they have been treated with fruquintinib for refractory mCRC. Other aims are to learn how safe fruquintinib is and how well it is tolerated by participants. Participants will receive fruquintinib in 4-week treatment cycles until their condition worsens, they do no longer tolerate the treatment or stop the treatment for other reasons. After the last treatment, participants will be checked upon every 3 months until study completion.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Nilesh Verma
ALL
18 Years to old
PHASE4
NCT06562543
STU-2024-0987
Inclusion Criteria:
• Provide written (or electronic) informed consent.
• Male or female aged more than or equal to (≥)18 years.
• Presence of histologically and/or cytologically documented metastatic colorectal adenocarcinoma. Rat sarcoma virus (RAS) status for each participant must be documented.
• Have been previously treated with standard approved therapies: * Fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, * An anti-vascular endothelial growth factor (VEGF) biological therapy (e.g., bevacizumab, aflibercept, ramucirumab \[regorafenib is NOT an anti-VEGF biologic\]), and * If RAS wild-type and medically appropriate, an anti-epidermal growth factor receptor (EGFR) therapy (e.g., cetuximab, panitumumab). * If known microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumor and medically appropriate, a programmed cell death protein 1 (PD1) inhibitor.
• Self-identify as Black and/or African American or Hispanic and/or Latino or as both.
• Body weight ≥40 kilograms (kg).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at screening.
• Have assessable disease according to RECIST version 1.1, assessed locally.
• In participants of childbearing potential, agreement to use highly effective form(s) of contraception, which results in a low failure rate (less than \[\<\]1 percent \[%\] per year) when used consistently and correctly, starting during the screening period, continuing throughout the entire trial period, and for 2 weeks after taking the last dose of the trial intervention. Such methods include oral (PO) hormonal contraception (combined estrogen/progestogen or progestogen-only) associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system (IUS), bilateral tubal ligation, vasectomized partner, or true sexual abstinence in line with the preferred and usual lifestyle of the participant. Those assigned male sex at birth must always use a condom.
Exclusion Criteria:
• Absolute neutrophil count (ANC) \<1.5 times 10\^9 per liter (10\^9/L), platelet count \<100 times 10\^9/L, or hemoglobin \<9.0 grams per deciliter (g/dL). Blood transfusion within 1 week prior to enrollment for the purpose of increasing the likelihood of eligibility is not allowed.
• Serum total bilirubin more than (\>)1.5 times the upper limit of normal range (ULN). Participants with previously documented Gilbert syndrome and bilirubin \<2 times ULN are eligible.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.5 times ULN in participants without hepatic metastases; ALT or AST \>5 times ULN in participants with hepatic metastases.
• Creatinine clearance \<30 milliliters per minute (mL/min). Creatinine clearance can either be measured in a 24-hour urine collection or estimated by the Cockcroft-Gault equation. Where available and appropriate, other formulae may be used to estimate clearance after consultation with the trial medical monitor.
• Urine dipstick or urinalysis with protein ≥2 positive or 24-hour urine protein ≥1.0 gram per 24 hours (g/24 hours). Participants with 1+ positive proteinuria must undergo a 24-hour urine collection to assess urine protein level.
• Uncontrolled hypertension, defined as systolic BP ≥140 millimeter of mercury (mmHg) and/or diastolic blood pressure (BP) ≥90 mmHg despite optimal medical management. The participant must have BP below both limits. Repeated assessments are permitted.
• International normalized ratio (INR) \>1.5 times ULN or activated partial thromboplastin time (aPTT) \>1.5 times ULN, unless the participant is currently receiving or intended to receive anticoagulants for prophylactic purposes.
• History of or active gastric/duodenal ulcer or ulcerative colitis, active hemorrhage of an unresected gastrointestinal tumor, history of perforation or fistulas, or any other condition that could, in the investigator's judgment, result in gastrointestinal hemorrhage or perforation within the 6 months prior to screening.
• History or presence of hemorrhage from any other site (e.g, hemoptysis or hematemesis) within 2 months prior to screening.
• History of a thromboembolic event, including deep vein thrombosis, pulmonary embolism, or arterial embolism within 6 months prior to screening.
• Stroke and/or transient ischemic attack within 12 months prior to screening.
• Clinically significant cardiovascular disease, including but not limited to, acute myocardial infarction or coronary artery bypass surgery within 6 months prior to enrollment, severe or unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, ventricular arrhythmias requiring treatment, or left ventricular ejection fraction \<50% by echocardiogram.
• QT interval, corrected using the Fridericia method (QTcF) \>480 milliseconds or any factors that increase the risk of QT interval, corrected based on the patient's heart rate (QTc) prolongation or risk of arrhythmic events such as hypokalemia, congenital long QT syndrome, or family history of long QT syndrome.
• Systemic antineoplastic therapies (except for that described in exclusion criterion no. 15) or any investigational therapy within 2 weeks prior to the first dose of the trial intervention, including chemotherapy, radical radiotherapy, hormonotherapy, biotherapy, and immunotherapy.
• Systemic small molecule targeted therapies (e.g., tyrosine kinase inhibitors \[TKIs\]) within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of the trial intervention.
• Palliative radiotherapy for bone metastasis/lesion within 2 weeks prior to the initiation of the trial intervention.
• Brachytherapy (i.e., implantation of radioactive seeds) within 60 days prior to the first dose of the trial intervention.
• Surgery or invasive procedure (i.e., a procedure that includes a biopsy; central venous catheter placement is allowed) within 14 days prior to the first dose of the trial intervention or unhealed surgical incision.
• Any unresolved toxicities from previous antitumor treatments greater than NCI CTCAE, version 5.0, Grade 1 (except for alopecia or neurotoxicity Grade less than or equal to \[≤\]2).
• Known human immunodeficiency virus infection.
• Known history of active viral hepatitis. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load had to be undetectable on suppressive therapy, if indicated. Participants with hepatitis C virus (HCV) infection who are currently on treatment are eligible if they have an undetectable HCV viral load.
• Clinically uncontrolled active infection requiring intravenous (IV) antibiotics.
• Tumor invasion of a large vascular structure (e.g., pulmonary artery or superior or inferior vena cava).
• Those who are currently pregnant or lactating.
• Brain metastases and/or spinal cord compression untreated with surgery and/or radiotherapy, and without clinical imaging evidence of SD for 14 days or longer; participants requiring steroids within 4 weeks prior to the start of the trial intervention are to be excluded.
• Other malignancy, except for non-melanoma skin cancer, in situ cervical carcinoma, or bladder carcinoma (tumor in situ and T1) that had been adequately treated during the 5 years prior to screening. Participants with another primary malignancy that has been adequately treated may be included after consultation with the trial medical monitor.
• Inability to take medication PO, dysphagia, or an active gastric ulcer resulting from previous surgery (e.g., gastric bypass) or a severe gastrointestinal disease, or any other condition that investigators believe might affect absorption of the investigational medicinal product (IMP).
• Other disease, metabolic disorder, physical examination anomaly, abnormal laboratory result, or any other condition (e.g., current alcohol or drug abuse) that investigators suspect might prohibit use of the IMP, affect interpretation of trial results, or put the participant at undue risk of harm based on the investigator's assessment.
• Known hypersensitivity to fruquintinib or any of its inactive ingredients, including the azo dyes Tartrazine- Federal Food, Drug, and Cosmetic Act (FD\&C) Yellow 5 and Sunset yellow For Coloring Food (FCF)-FD\&C Yellow 6.
• Received prior fruquintinib.
• Live vaccine ≤28 days before the first dose of the trial intervention. Seasonal vaccines for influenza are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed.
• Use of strong inducers of cytochrome P450 3A4 (CYP3A4) within 2 weeks before the first dose of the trial intervention.
DRUG: Fruquintinib
Colorectal Cancer, Colon, Rectum
colorectal cancer, fruquintinib
UT Southwestern; Parkland Health & Hospital System
A Study of KK2269 in Adult Participants With Solid Tumors
This is a first-in-human study of KK2269. Part 1 and Part 2 will be conducted as a multicenter, open-label, non-randomized, dose-escalation study. Participants with advanced or metastatic solid tumors for which no standard therapy is available will be enrolled in Part 1. In Part 1, the primary objective is to assess the safety and tolerability of KK2269. In Part 2, only participants with gastric adenocarcinoma, GEJ adenocarcinoma, esophageal adenocarcinoma, or NSCLC who have experienced at least one systemic therapy will be enrolled. In Part 2, the primary objective is to assess the safety and tolerability of KK2269 in combination with docetaxel and to determine the recommended dose(s) and dose interval(s) of KK2269 in combination with docetaxel for subsequent studies. In both Part 1 and Part 2, participants who refuse to undergo standard therapy are also eligible.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Timothy Brown
ALL
18 Years to old
PHASE1
NCT06266299
STU-2024-1166
* Key Common Inclusion Criteria for Parts 1 and 2:
* Patients who are ≥ 18 years old at the time of informed consent
* Patients who have disease measurable by RECIST v1.1
* Patients with an ECOG PS of 0 or 1
* Patients with a life expectancy of at least 3 months in the judgement of the investigator or subinvestigator
* The specified periods have passed respectively after the completion of previous cancer treatments as of the date of enrollment at the time of the first dose of KK2269
* Patients who agree to use a medically effective method of contraception
* Key Additional Inclusion Criterion for Part 1:
•Patients with histological or cytological evidence of at least one locally advanced or metastatic non-CNS solid tumor
* Key Additional Inclusion Criteria for Part 2:
•Patients with histological or cytological evidence of any of the following disease: Gastric adenocarcinoma, GEJ adenocarcinoma, or esophageal adenocarcinoma, NSCLC (Only patients with NSCLC will be enrolled in the expansion part)
•Patients who are suitable for docetaxel treatment
* Key Common Exclusion Criteria for Parts 1 and 2:
* Patients with an uncontrolled or serious intercurrent illness
* Patients with known active central nervous system metastasis
* Patients with a history of ≥ Grade 3 allergic reaction to any antibody drug
* Patients with a history of autoimmune disease
* Patients with a history of HIV, HBV, or HCV at screening
* Patients who have a history of primary immunodeficiency
* Key Additional Exclusion Criterion For Part 2:
* Patients with a history of treatment with docetaxel
DRUG: KK2269, DRUG: Docetaxel
Advanced Solid Tumor, Metastatic Solid Tumor, Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Esophageal Adenocarcinoma, Non Small Cell Lung Cancer, Esophagus, Lung/Thoracic, Other Digestive Organ
UT Southwestern
National Liver Cancer Screening Trial (TRACER)
The National Liver Cancer Screening Trial is an adaptive randomized phase IV Trial comparing ultrasound-based versus biomarker-based screening in 5500 patients with cirrhosis from any etiology or patients with chronic hepatitis B infection. Eligible patients will be randomized in a 1:1 fashion to Arm A using semi-annual ultrasound and AFP-based screening or Arm B using semi-annual screening using GALAD alone. Randomization will be stratified by sex, enrolling site, Child Pugh class (A vs. B), and HCC etiology (viral vs. non-viral). Patients will be recruited from 15 sites (mix of tertiary care and large community health systems) over a 3-year period, and the primary endpoint of the phase IV trial, reduction in late-stage HCC, will be assessed after 5.5 years.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Amit Singal
ALL
18 Years to 85 Years old
PHASE4
NCT06084234
STU-2023-0842
Inclusion Criteria:
Patient must meet all of the following inclusion criteria:
• Adult patients ages 18-85 with cirrhosis from any etiology or with chronic hepatitis B with a PAGE-B score greater than 9 within 12 months of enrollment
• Patient is eligible for HCC surveillance according to treating physician or by the site investigator
• Able to provide informed consent
• Life expectancy \>6 months (after consent) as determined by the treating provider or site investigator
Exclusion Criteria:
Patient will be excluded for any of the following exclusion criteria:
• Child Pugh C cirrhosis
• History or clinical symptoms of hepatocellular carcinoma or cholangiocarcinoma
• History of solid nodule on baseline ultrasound (i.e., lesion 1cm or greater) within 9 months prior to consent without subsequent diagnostic CT/MRI demonstrating benign nature)
• AFP \>20 ng/mL within 6 months prior to consent, in the absence of a contrast-enhanced CT or MRI within 6 months of AFP (before or after) level demonstrating lack of suspicious liver lesions
• Newly diagnosed LR-3 greater than or equal to 1 cm within 6 months prior to consent
• History of LR-4, LR-5, or LR-M on multi-phase CT or contrast-enhanced MRI within 6 months prior to consent
• Presence of another active cancer besides non-melanomatous skin cancer or indolent cancer under active surveillance (e.g., prostate cancer or renal cell carcinoma) within the 2 years prior to consent
• Patient's provider is planning to use MRI- or CT- based surveillance moving forward
• History of a transjugular intrahepatic portosystemic shunt (TIPS)
• History of Fontan associated liver disease or cardiac cirrhosis
• History of solid organ transplantation
• Actively listed for liver transplantation
• Diagnosis of alcohol-associated hepatitis within 3 months prior to consent
• Documented current or continued signs and symptoms of acute Wilson disease (acute liver failure, acute neurological deficits, hemolysis)
• In patients with primary sclerosing cholangitis (PSC): Current active cholangitis within 90 days prior to consent
• Known or documented habitual non-adherence to previous research studies or medical procedures or unwillingness to adhere to protocol (e.g., unwilling to obtain consent or samples)
• In patients living with HIV: CD4+ T cell count less than 100 cells/mm3 within 60 days prior to consent
• Known pregnancy at consent
• Active warfarin use
DIAGNOSTIC_TEST: GALAD, DIAGNOSTIC_TEST: Liver Ultrasound with or without AFP
Carcinoma, Hepatocellular, Liver Cancer, Liver Cirrhosis, Hepatitis B, Liver
Hepatocellular carcinoma surveillance, GALAD, Alpha Fetoprotein
UT Southwestern; Parkland Health & Hospital System
Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis (AFFIRM)
To Evaluate the Effect of Seladelpar on Clinical Outcomes in Patients with Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis.
Call 214-648-5005
studyfinder@utsouthwestern.edu, lakeisha.johnson@utsouthwestern.edu
Marlyn Mayo
ALL
18 Years to 75 Years old
PHASE3
NCT06051617
STU-2023-0826
Inclusion Criteria:
Individuals must meet the following criteria to be eligible for study participation:
• Must be at least 18 years old.
• Must have a confirmed prior diagnosis of PBC
• Evidence of cirrhosis
• CP Score A or B
• Females of reproductive potential must use at least 1 barrier contraceptive and a second effective birth control method during the study and for at least 90 days after the last dose. Male individuals 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
• Individuals must be able to comply with the instructions for study drug administration and be able to complete the study schedule of assessments (SOA)
Exclusion Criteria:
Individuals must not meet any of the following criteria to be eligible for study participation:
• Prior exposure to seladelpar
• A medical condition other than PBC that, in the Investigator's opinion, would preclude full participation in the study
• History of liver transplantation or actively listed for cadaveric or planned living donor transplant.
• Decompensated cirrhosis
• Evidence of portal vein thrombosis based on imaging at time of Screening by Doppler ultrasound or prior evidence by CT or MRI
• Hospitalization for liver-related complication within 12 weeks of Screening
• Laboratory parameters at Screening:
• Alkaline phosphatase (ALP) \< 1.5× Upper limit of normal (ULN) or ≥ 10×ULN
• Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) ≥5×ULN
• Total bilirubin (TB) ≤ 0.6 × ULN or ≥ 5 × ULN
• Platelet count ≤50×10\^3/µL
• Albumin ≤2.8 g/dL
• Estimated glomerular filtration rate (eGFR) \<45 mL/min/1.73 m\^2
• MELD score \>12. For individuals on anticoagulation medication, baseline International normalized ratio (INR) determination for MELD score calculation should take anticoagulant use into account, in consultation with the Medical Monitor.
• Serum alpha-fetoprotein (AFP) \>20 ng/mL
• INR \>1.7
• CP-C cirrhosis
• History or presence of other concomitant liver diseases
DRUG: Seladelpar, DRUG: Placebo
Primary Biliary Cholangitis, Liver
Primary Biliary Cholangitis (PBC), PBC
UT Southwestern; Parkland Health & Hospital System
EGCG for Hepatocellular Carcinoma Chemoprevention (CATCH-B)
This phase II trial tests epigallocatechin gallate (EGCG) for its efficacy and safety in preventing development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yujin Hoshida
ALL
18 Years to old
PHASE2
NCT06015022
STU-2023-0233
Inclusion Criteria:
* Adults (≥ 18 years-old)
* Clinically and/or histologically diagnosed cirrhosis
* No active hepatic decompensation
* No prior history of HCC
* Adequate hematologic, hepatic, and renal function
* Karnofsky performance status score ≥70
* Both sexes and all racial/ethnic groups will be considered
* FIB-4 index \> 3.25
* High-risk PLSec at baseline
* Absence of HLA-B\*35:01
Exclusion Criteria:
* Prior or ongoing use of EGCG
* History of adverse reaction to green tea products
* Severe obesity (BMI \> 40 kg/m2)
* Active drinking
* EGCG treatment \<4 weeks or \<80% of planned regimen at the end of week 4
* HCC development during the study DRUG: Epigallocatechin gallate (EGCG), OTHER: Placebo
Cirrhosis, Liver, Liver
hepatocellular carcinoma, chemoprevention, liver cancer
UT Southwestern; Parkland Health & Hospital System
Testing Pump Chemotherapy in Addition to Standard of Care Chemotherapy Versus Standard of Care Chemotherapy Alone for Patients With Unresectable Colorectal Liver Metastases: The PUMP Trial
This phase III trial compares hepatic arterial infusion (HAI) (pump chemotherapy) in addition to standard of care chemotherapy versus standard of care chemotherapy alone in treating patients with colorectal cancer that has spread to the liver (liver metastases) and cannot be removed by surgery (unresectable). HAI uses a catheter to carry a tumor-killing chemotherapy drug called floxuridine directly into the liver. HAI is already approved by the Food and Drug Administration (FDA) for use in metastatic colorectal cancer to the liver, but it is only available at a small number of hospitals, and most of the time it is not used until standard chemotherapy stops working. Standard chemotherapy drugs 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. Adding HAI to standard chemotherapy may be effective in shrinking or stabilizing unresectable colorectal liver metastases.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Cecilia Ethun
ALL
18 Years and over
PHASE3
NCT05863195
STU-2024-0075
Inclusion Criteria:
* Patient must be \>= 18 years of age
* Patient must have confirmed unresectable liver confined metastatic colorectal cancer (CRC).
* Patient must not have radiographically or clinically evident extrahepatic disease (including but not limited to radiographically positive periportal lymph nodes).
* NOTE: Patients found to have positive periportal nodes at the time of HAI placement can remain on study.
* Patient may have calcified pulmonary nodules, and/or =\< 5 indeterminate and stable (for a minimum of 3 months on chemotherapy) pulmonary nodules each measuring =\< 6 mm in maximal axial dimension.
* Patient's primary tumor may be in place.
* Patient must have received 3-6 months of previous first-line chemotherapy that meet one of the following three criteria: a) have received at least 6 but no more than 12 cycles of first-line cytotoxic chemotherapy (where 1 cycle = 14 days) OR b) have received at least 4 but no more than 8 cycles of first-line cytotoxic chemotherapy (where 1 cycle = 21 days) OR c) have developed new colorectal liver metastases (CRLM) within 12 months of completing adjuvant systemic therapy for stage II-III colorectal cancer.
* NOTE: First-line chemotherapy may have included any of the following regimens as listed in the National Comprehensive Cancer Network (NCCN) Guidelines: leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX) (or equivalent), leucovorin calcium (calcium folinate), 5-fluorouracil, and irinotecan (FOLFIRI) (or equivalent), leucovorin calcium (calcium folinate), 5-fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI), each with or without any of the following: bevacizumab, cetuximab, or panitumumab.
* Patient must have stable or responding disease on first-line chemotherapy by RECIST 1.1 criteria
* Patient must meet the following criteria for technical unresectability:
* A margin-negative resection requires resection of three hepatic veins, both portal veins, or the retrohepatic vena cava OR a resection that leaves less than two adequately perfused and drained segments.
* NOTE: Institutional multidisciplinary review is required to confirm unresectability and rule out radiographically positive extrahepatic disease.
* Patient must undergo CT angiography (chest/abdomen/pelvis) to confirm acceptable hepatic arterial anatomy for HAI and to rule out extrahepatic disease within 4 weeks prior to randomization.
* Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 and be clinically fit to undergo surgery as determined by the pre-operative evaluation.
* Leukocytes \>= 3,000/mcL (obtained =\< 14 days prior to protocol randomization)
* Absolute neutrophil count (ANC) \>= 1,500/mcL (obtained =\< 14 days prior to protocol randomization)
* Platelets \>= 100,000/mcL (obtained =\< 14 days prior to protocol randomization)
* Total Bilirubin =\< 1.5 mg/dL (obtained =\< 14 days prior to protocol randomization)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) =\< 3.0 x institutional upper limit of normal (ULN) (obtained =\< 14 days prior to protocol randomization)
* Creatinine =\< 1.5 x institutional ULN OR creatinine clearance \>= 50 mL/min calculated by the Cockcroft-Gault method (obtained =\< 14 days prior to protocol randomization)
* Calcium \>= institutional lower limit of normal (LLN)
* 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.
* 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. Testing for HIV is not required for entry onto the study
Exclusion Criteria:
* Patient must not have a liver tumor burden exceeding 70% of total liver volume.
* Patient must not have had prior radiation to the liver (prior radiation therapy to the pelvis is acceptable if completed at least 2 weeks prior to randomization).
* Patient must not have had prior trans-arterial bland embolization, chemoembolization (TACE) or radioembolization (TARE).
* Patient must not have had prior treatment with HAI/floxuridine (FUDR)
* Patient must not have microsatellite instability-high (MSI-H) colorectal cancer.
* Patient must not have CRLM that could be resected with 2-stage hepatectomy, including associating liver partition and portal vein ligation (ALPPS).
* Patient must not have an active infection, serious or non-healing active wound, ulcer, or bone fracture.
* Patient must not have any serious medical problems which would preclude receiving the protocol treatment or would interfere with the cooperation with the requirements of this trial.
* Patient must not have cirrhosis and/or clinical or radiographic evidence of portal hypertension
* Patient 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 patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy.
* A patient of childbearing potential is defined as anyone, 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).
* Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study. BIOLOGICAL: Bevacizumab, BIOLOGICAL: Cetuximab, PROCEDURE: Computed Tomography, DRUG: Floxuridine, DRUG: Fluorouracil, PROCEDURE: Implantation, PROCEDURE: Intrahepatic Infusion Procedure, DRUG: Irinotecan, DRUG: Leucovorin, DRUG: Oxaliplatin, BIOLOGICAL: Panitumumab, PROCEDURE: Single Photon Emission Computed Tomography
Metastatic Colorectal Carcinoma, Metastatic Malignant Neoplasm in the Liver, Stage IV Colorectal Cancer AJCC v8, Unresectable Colorectal Carcinoma, Colon, Liver, Rectum
UT Southwestern; Parkland Health & Hospital System
A Study With Tovorafenib (DAY101) as a Treatment Option for Progressive, Relapsed, or Refractory Langerhans Cell Histiocytosis
This phase II trial tests the safety, side effects, best dose and activity of tovorafenib (DAY101) in treating patients with Langerhans cell histiocytosis that is growing, spreading, or getting worse (progressive), has come back (relapsed) after previous treatment, or does not respond to therapy (refractory). Langerhans cell histiocytosis is a type of disease that occurs when the body makes too many immature Langerhans cells (a type of white blood cell). When these cells build up, they can form tumors in certain tissues and organs including bones, skin, lungs and pituitary gland and can damage them. This tumor is more common in children and young adults. DAY101 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Using DAY101 may be effective in treating patients with relapsed or refractory Langerhans cell histiocytosis.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Erin Butler
ALL
180 Days to 22 Years old
PHASE2
NCT05828069
STU-2023-0818
Inclusion Criteria:
* 180 days- \< 22 years (at time of study enrollment)
* Patient must have a body surface area of ≥ 0.3 m\^2
* Patients with progressive, relapsed, or recurrent LCH with measurable disease at study entry
* Patients must have had histologic verification of LCH (from either original diagnosis or relapse/progression) at the time of study entry
* Tissue confirmation of relapse is recommended but not required.
* Pathology report must be submitted for central confirmation of diagnosis within 7 days of enrollment.
* Formalin-fixed paraffin-embedded (FFPE) blocks or unstained slides (initial diagnosis and/or subsequent biopsies) will be required for retrospective central confirmation of diagnosis and molecular studies
* Patients with mixed histiocytic disorders (e.g. LCH with juvenile xanthogranuloma) may be included
* Patients must have measurable disease
* Patients must have progressive or refractory disease or experience relapse after at least one previous systemic treatment strategy
* Pathogenic somatic mutation detected in genes encoding tyrosine kinase receptors (CSFR1, ERBB3 or ALK), RAS or RAF (may be from original or subsequent biopsy or peripheral blood/bone marrow aspirate). Clinical mutation reports may include quantitative polymerase chain reaction (PCR) (e.g. BRAFV600E) and/or Sanger or next generation sequencing. Immunohistochemistry (e.g. VE1 antibody for BRAFV600E) alone is not sufficient
* Participant must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet, which may be taken by mouth or other enteral route such as nasogastric, jejunostomy, or gastric tube
* Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50% for patients =\< 16 years of age
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Myelosuppressive chemotherapy: Patients must not have received within 14 days of entry onto this study
* Investigational agent or any other anticancer therapy not defined above: Patients must not have received any investigational agent or any other anticancer therapy (including MAPK pathway inhibitor) for at least 14 days prior to planned start of tovorafenib (DAY101)
* Radiation therapy (RT): Patient must not have received RT within 2 weeks after the last dose fraction of RT
* Patients must have fully recovered from any prior surgery
* Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, targeted inhibitor, and/or radiotherapy with toxicities reduced to grade 1 or less (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0)
* Steroids: =\< 0.5 mg/kg/day of prednisone equivalent (maximum 20 mg/day) averaged during the month prior to study enrollment is permissible
* Strong inducers or inhibitors of CYP2C8 are prohibited for 14 days before the first dose of tovorafenib (DAY101) and from planned administration for the duration of study participation
* Medications that are breast cancer resistant protein (BCRP) substrates that have a narrow therapeutic index are prohibited for 14 days before the first dose of tovorafenib (DAY101) and for the duration of study participation
* Peripheral absolute neutrophil count (ANC) \>= 750/uL unless secondary to bone marrow involvement, in such cases bone marrow involvement must be documented (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* Platelet count \>= 75,000/uL (unsupported/without transfusion within the past 7 days) (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* Patients with marrow disease must have platelet count of \>= 75,000/uL (transfusion support allowed) and must not be refractory to platelet transfusions. Bone marrow involvement must be documented
* Hemoglobin \>= 8 g/dL (unsupported/without transfusion within the past 7 days). Patients with marrow disease must have hemoglobin \>= 8 g/dL (transfusion support allowed). Bone marrow involvement must be documented
* Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g., Neulasta \[registered trademark\]) or 7 days for short-acting growth factor
* A serum creatinine based on age/sex as follows (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* Age: 6 months to \< 1 year; Maximum Serum Creatinine (mg/dL):= 0.5 mg/dl (male and female)
* Age: 1 to \< 2 years; Maximum Serum Creatinine (mg/dL): = 0.6 mg/dl (male and female)
* Age: 2 to \< 6 years; Maximum Serum Creatinine (mg/dL): = 0.8 mg/dl (male and female)
* Age: 6 to \< 10 years; Maximum Serum Creatinine (mg/dL): = 1.0 mg/dl (male and female)
* Age: 10 to \< 13 years; Maximum Serum Creatinine (mg/dL): = 1.2 mg/dl (male and female)
* Age: 13 to \< 16 years; Maximum Serum Creatinine (mg/dL): = 1.5 mg/dl (male) and 1.4 mg/dl (female)
* Age: \>= 16 years; Maximum Serum Creatinine (mg/dL): = 1.7 mg/dl (male) and 1.4 mg/dl (female)
* OR- a 24 hour urine creatinine clearance \>= 50 mL/min/1.73 m\^2
* OR- a glomerular filtration rate (GFR) \>= 50 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
* Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* Bilirubin (sum of conjugated + unconjugated) =\< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* Alanine aminotransferase (ALT) =\< 3 x ULN for age (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* Serum albumin \>= 2 g/dl must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* For patients with liver disease caused by their histiocytic disorder (as evaluated on radiographic imaging or biopsy): patients may be enrolled with abnormal bilirubin, aspartate aminotransferase (AST), ALT and albumin with documentation of histiocytic liver disease
* Fractional shortening (FS) of \>= 25% or ejection fraction of \>= 50%, as determined by echocardiography or multigated acquisition scan (MUGA) within 28 days prior to study enrollment. Depending on institutional standard, either FS or left ventricular ejection fraction (LVEF) is adequate for enrollment if only one value is measured; if both values are measured, then both values must meet criteria above (must be obtained within 28 days prior to enrollment and start of protocol therapy) (repeat if necessary)
* No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \> 94% if there is clinical indication for determination; unless it is due to underlying pulmonary LCH
* Central Nervous System Function Defined As:
* Patients with seizure disorder may be enrolled if well controlled
* Central nervous system (CNS) toxicity =\< Grade 2
* Human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial unless antiretroviral therapy interacts with the metabolism of tovorafenib (DAY101) and cannot safely be changed to antivirals that do not interact with study medication
* All patients and/or their parent(s) or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
Exclusion Criteria:
* LCH arising along with other hematologic malignancy (e.g. mixed LCH with acute lymphoblastic leukemia) or any history of non-histiocytic malignancy
* Disease scenarios as below will be excluded
* Skin-limited disease
* Gastrointestinal (GI) tract involvement only (those that have disease that can be determined by endoscopic biopsies only)
* LCH-associated neurodegeneration (LCH-ND) without parenchymal lesions or other systemic lesions
* Patients with activating mutations in MAP2K1 are not eligible for this study due to drug target specificity. Mutation status will be submitted to study team within 7 days of enrollment
* Refractory nausea and vomiting, malabsorption, or external biliary shunt that would preclude adequate absorption of tovorafenib (DAY101)
* Uncontrolled systemic bacterial, viral, or fungal infection
* Major surgical procedure or significant traumatic injury within 14 days prior to study enrollment, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within fourteen (14) days of study enrollment (provided that the wound has healed)
* History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease
* Ophthalmologic considerations: Patients with known significant ophthalmologic conditions or known risk factors for retinal vein occlusion (RVO) or central serous retinopathy (CSR) are not eligible
* History of solid organ or hematopoietic bone marrow transplantation
* Clinically significant active cardiovascular disease, or history of myocardial infarction, or deep vein thrombosis/pulmonary embolism within 6 months prior to enrollment, ongoing cardiomyopathy, or current prolonged QT interval \> 440 ms based on triplicate electrocardiogram (ECG) average
* History of Grade \>= 2 CNS hemorrhage or history of any CNS hemorrhage within 28 days of study entry
* History of any drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome or Stevens Johnsons syndrome (SJS) or who are allergic to tovorafenib (DAY101) or any of its components
* CTCAE version (V.) 5.0 Grade 3 symptomatic creatinine kinase (CPK) elevation (\> 5 x ULN)
* Female patients who are pregnant are ineligible. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants are ineligible
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation are ineligible. Women of childbearing potential must use non-hormonal contraception during tovorafenib treatment and for at least 28 days after the last dose. Men should use effective contraception and must not father a child while taking tovorafenib and for 14 days after the last dose PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, PROCEDURE: FDG-Positron Emission Tomography and Computed Tomography Scan, PROCEDURE: Lumbar Puncture, PROCEDURE: Multigated Acquisition Scan, DRUG: Tovorafenib
Recurrent Langerhans Cell Histiocytosis, Refractory Langerhans Cell Histiocytosis, Bones and Joints, Other Skin, Brain and Nervous System, Liver, Lung/Thoracic, Other Hematopoietic, Small Intestine
Children’s Health
mFOLFIRINOX Versus mFOLFOX With or Without Nivolumab for the Treatment of Advanced, Unresectable, or Metastatic HER2 Negative Esophageal, Gastroesophageal Junction, and Gastric Adenocarcinoma
This phase III trial compares the effect of modified fluorouracil, leucovorin calcium, oxaliplatin, and irinotecan (mFOLFIRINOX) to modified fluorouracil, leucovorin calcium, and oxaliplatin (mFOLFOX) for the treatment of advanced, unresectable, or metastatic HER2 negative esophageal, gastroesophageal junction, and gastric adenocarcinoma. The usual approach for patients is treatment with FOLFOX chemotherapy. Chemotherapy drugs 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. Fluorouracil stops cells from making DNA and it may kill tumor cells. Leucovorin is used with fluorouracil to enhance the effects of the drug. Oxaliplatin works by killing, stopping, or slowing the growth of tumor cells. Some patients also receive an immunotherapy drug, nivolumab, in addition to FOLFOX chemotherapy. Immunotherapy may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Irinotecan blocks certain enzymes needed for cell division and DNA repair, and it may kill tumor cells. Adding irinotecan to the FOLFOX regimen could shrink the cancer and extend the life of patients with advanced gastroesophageal cancers.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Timothy Brown
ALL
18 Years to old
PHASE3
NCT05677490
STU-2024-0324
Inclusion Criteria:
* Histologic documentation: HER2 negative adenocarcinoma as defined by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines (Bartley et al., Journal of Clinical Oncology \[JCO\] 2017) with known PD-L1 CPS (Any CPS is allowed, but should be known prior to registration)
* Stage: unresectable or metastatic
* Tumor site: esophagus, gastroesophageal junction, or stomach
* Measurable disease or non-measurable but evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* No prior treatment for unresectable or metastatic disease
* Prior neoadjuvant or adjuvant cytotoxic chemotherapy or adjuvant immunotherapy is allowed as long as it was completed at least 1 year prior to registration
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Creatinine =\< 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance \>= 30 mL/min
* Total bilirubin =\< 1.5 x ULN
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x ULN (in patients with liver metastasis: =\< 5 x ULN if clearly attributable to liver metastases)
* 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 positive for human immunodeficiency virus (HIV) are eligible only if they meet all of the following:
* On effective anti-retroviral therapy
* Undetectable HIV viral load by standard clinical assay =\< 6 months of registration
* 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
* Patients who will receive nivolumab in addition to chemotherapy must not have any contraindications to immune checkpoint inhibitors
* Patients must not have active autoimmune disease that has required systemic treatment within 6 months prior to registration. Patients are permitted to receive immunotherapy if they have vitiligo, type I diabetes, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)
* Patients must not have a condition requiring systemic treatment with either corticosteroids (\>10mg/day prednisone equivalents) or other immunosuppressive medications within 14 days prior to registration. Inhaled or topical steroids and adrenal replacement doses (=\< 10mg/day prednisone equivalent) are permitted
* Patients must not have a history of noninfectious pneumonitis requiring steroids
* Patients with prior immune mediated adverse events related to immunotherapy that resulted in permanent treatment discontinuation with these agents are ineligible
* This study includes the use of the mandatory patient completed measure, PRO-CTCAE. For this study the PRO-CTCAE is available in English, Spanish, Korean, Chinese (Simplified), and Russian, hence patients must be able to speak, understand and read in these languages. Ad-hoc translation of patient-reported measures is not permitted
Exclusion Criteria:
* 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 serum or urine pregnancy test done =\< 7 days prior to registration is required
* No known Gilbert's syndrome or known homozygosity for UGAT1A1\*28 polymorphism
* No baseline grade \>= 2 peripheral neuropathy, neurosensory toxicity, or neuromotor toxicity per CTCAE version (v) 5.0 regardless of causality
* No medical condition such as uncontrolled infection or uncontrolled diabetes mellitus which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
* No untreated, symptomatic brain metastasis. Patients with treated brain metastases are eligible if the following criteria are met: 1) follow-up brain imaging done at least in 4 weeks after central nervous system (CNS)-directed therapy shows no evidence of progression and 2) the patient no longer requires steroids, or is on a stable steroid dose for more than four weeks
* No allogeneic tissue/organ transplant DRUG: Fluorouracil, DRUG: Leucovorin Calcium, DRUG: Oxaliplatin, DRUG: Irinotecan, BIOLOGICAL: Nivolumab, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Computed Tomography, PROCEDURE: Biospecimen Collection, OTHER: Questionnaire Administration
Advanced Esophageal Adenocarcinoma, Advanced Gastric Adenocarcinoma, Advanced Gastroesophageal Junction Adenocarcinoma, Clinical Stage III Esophageal Adenocarcinoma AJCC v8, Clinical Stage III Gastric Cancer AJCC v8, Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage IV Esophageal Adenocarcinoma AJCC v8, Clinical Stage IV Gastric Cancer AJCC v8, Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8, Metastatic Esophageal Adenocarcinoma, Metastatic Gastric Adenocarcinoma, Metastatic Gastroesophageal Junction Adenocarcinoma, Unresectable Esophageal Adenocarcinoma, Unresectable Gastric Adenocarcinoma, Unresectable Gastroesophageal Junction Adenocarcinoma, Esophagus, Stomach
UT Southwestern; Parkland Health & Hospital System
FORAGER-1: A Study of LOXO-435 (LY3866288) in Participants With Cancer With a Change in a Gene Called FGFR3 (FORAGER-1)
The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435 by itself or when it is combined with other standard medicines that treat cancer. LOXO-435 may be used to treat cancer of the cells that line the urinary system and other solid tumor cancers that have a change in a particular gene (known as the FGFR3 gene). Participation could last up to 30 months (2.5 years) and possibly longer if the disease does not get worse.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE1
NCT05614739
STU-2023-0080
Inclusion Criteria:
* Have solid tumor cancer with an FGFR3 pathway alteration on molecular testing in tumor or blood sample that is deemed as actionable
* Cohort A1: Presence of an alteration in FGFR3 or its ligands
* Cohort A2, B2, B3, and B5: Histological diagnosis of urothelial cancer (UC) that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration
* Cohorts B1 and B4: Histological diagnosis of urothelial cancer that is locally advanced or metastatic
* Cohort C1: Must have histological diagnosis of a non-urothelial solid tumor malignancy that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration
* Measurability of disease:
* Cohort A1 and B3: Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1)
* Cohorts A2, B1, B2, B4, B5, and C1: Measurable disease required as defined by RECIST v1.1
* Have adequate tumor tissue sample available. Participants with inadequate tissue sample availability may still be considered for enrollment upon review
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 for Cohorts A1, A2, B3, and B5
* Less than or equal to 2 for Cohorts B1, B2, B4, and C1
* Prior Systemic Therapy Criteria:
* Cohort A1/C1: Participant has received all standard therapies for which the participant was deemed to be an appropriate candidate by the treating Investigator; OR the participant is refusing the remaining most appropriate standard of care treatment; OR there is no standard therapy available for the disease. There is no restriction on number of prior therapies.
* Cohort A2, B2, B3 participants must have received at least one prior regimen, and cohorts B1 and B4 participants at least 2 prior regimens, in the locally advanced or metastatic setting
* There is no restriction on number of prior therapies
* Cohort B5: Participants have not received prior systemic therapy for locally advanced or metastatic UC
* FGFR inhibitor specific requirements:
* Cohort A1/A2/B3: Prior FGFR inhibitor treatment is permitted but not required
* Cohort B1/B4: Participants must have been previously treated with erdafitinib
* Cohort B2, B5, and C1: Participants must be FGFR inhibitor naïve
Exclusion Criteria:
* Participants with primary central nervous system (CNS) malignancy
* Untreated or uncontrolled CNS metastases
* Current evidence of corneal keratopathy or retinal disorder. Individuals with asymptomatic ophthalmic conditions may be eligible
* Any serious unresolved toxicities from prior therapy
* Significant cardiovascular disease
* Prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF)
* Active uncontrolled systemic infection or other clinically significant medical conditions
* Participants who are pregnant, lactating, or plan to breastfeed during the study or within 6 months of the last dose of study treatment. Participants who have stopped breastfeeding may be enrolled DRUG: LOXO-435, DRUG: Pembrolizumab, DRUG: enfortumab vedotin
Urinary Bladder Neoplasms, Neoplasm Metastasis, Ureteral Neoplasms, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Kaposis sarcoma, 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, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder
Bladder Cancer, Bladder Urothelial Carcinoma, Urinary Bladder Cancer, Urinary Tract Cancer, Renal Pelvis Cancer, Ureter Cancer
UT Southwestern; Parkland Health & Hospital System
Evaluate REC-4881 in Participants With Familial Adenomatous Polyposis (FAP) (TUPELO)
This is a multicenter, two-part trial in participants with FAP.
Call 214-648-5005
studyfinder@utsouthwestern.edu, YAMEI.CHENG@UTSouthwestern.edu
Luke Engelking
ALL
18 Years to old
PHASE1
NCT05552755
STU-2024-0553
Inclusion Criteria:
• Male or female and ≥ 18 years of age
• Have provided written informed consent to participate in the study
• Diagnosis of phenotypic classical FAP with disease involvement of the duodenum or the residual colon/rectum/pouch as the primary disease site.
• Genetic diagnosis of FAP with APC gene mutation (Part 2 only).
• Has undergone colectomy or subtotal colectomy
• Spigelman Classification Stage II or higher.
• Investigator/Participant agrees to leave polyps ≤10 mm unresected during endoscopies performed at Screening and while on study
• Have no significant cardiovascular abnormalities at Screening:
• Left ventricular ejection fraction \>50% as determined on screening echocardiogram (ECHO)/ multi-gated acquisition (MUGA)
• A QT interval corrected for heart rate using the Fridericia formula (QTcF) \< 450 msec in men and \<470 milliseconds (msec) in women.
• Have no significant hematopoietic abnormalities at Screening:
• White blood cell count (WBC) ≥ 3,000/cubic millimeters (mm\^3) (non-black populations); 2,700/mm\^3 (black populations)
• Platelet count ≥ 120,000/mm\^3
• Hemoglobin ≥ 10.0 grams (g)/deciiter (dL)
• No history of clinical coagulopathy.
• Have no significant hepatic abnormalities at Screening:
• Total bilirubin ≤ 1.5 \* upper limit of normal (ULN) (individuals with Gilbert syndrome may be enrolled)
• Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) ≤ 2.0 \* ULN.
• Have no significant renal abnormalities at Screening: serum creatinine ≤ 1.5 times \* ULN.
• Female participants who are women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours before the first dose of study drug. If the urine test is positive or cannot be confirmed negative, a serum pregnancy test will be required and must be negative for the participant to be eligible.
• All participants must be willing to follow the contraceptive guidance in the protocol and must not be lactating or planning to attempt to become pregnant during the study or for a further period of 4 months after the last dose of study drug or impregnate someone during this study or for a further period of 14 weeks after the last dose of study drug.
• Absence of gross blood in stool at Screening; red blood on toilet paper only is acceptable.
• Participant must be willing to discontinue use of non-steroidal anti-inflammatory agents (NSAIDs) 6 weeks prior to Study Day 1 and remain off NSAIDs throughout the treatment period of the study (use of aspirin ≤ 700 milligrams \[mg\] week is allowed.)
Exclusion Criteria:
• Has any clinically significant laboratory abnormality, medical or psychiatric illness which, in the opinion of the Investigator, could interfere with the conduct or interpretation of the study or put the participant at risk.
• Has had prior pelvic irradiation.
• Has gastrointestinal disease or recent gastrointestinal procedure that could interfere with oral absorption of REC-4881, including difficulty swallowing capsules.
• Has received treatment with other investigational agents within the 4 weeks prior to Study Day 1 or a period during which the investigational agent has not been cleared from the body (that is, at least a period of 5 half-lives, if known), whichever is longer.
• Treatment with other FAP-directed drug therapy (such as off-label use of Balsalazide) within 8 weeks of screening endoscopy (Part 2 only) or had a Whipple procedure.
• Is currently under treatment for desmoid tumors.
• Use of omega-3 fatty acids or oral corticosteroids prior to Study Day 1
• Use of strong cytochrome P3A (CYP3A) inhibitors or inducers prior to Study Day 1
• History of an ongoing or newly diagnosed eye abnormality, including:
• Retinal pathologies such as diabetic retinopathy, veno-occlusion, or macular edema
• Corneal pathologies such as herpes keratitis, corneal dystrophy, corneal erosions, corneal degeneration, active or recurrent keratitis, or uveitis (intermittent, posterior, and/or panuveitis)
• Other clinically significant ophthalmologic abnormalities (for example, retinal detachment) or has findings at Screening. \[Participants with corrected myopia may be enrolled.\]
• Has cancer at screening endoscopy in gastrointestinal (GI) tract (including stomach, duodenum, and colon/rectum/pouch) (Part 2 only).
• Has a large polyp (\>1 centimeter \[cm\]) not amenable to complete removal
• Has active pancreatitis secondary to pancreatic duct obstruction
• Has active gall bladder disease
• Is pregnant, lactating or is planning to attempt to become pregnant during this study or within 4 months after the last dose of study drug (women) or is planning to attempt to impregnate someone or donate sperm during the study or within 14 weeks after the last dose of study drug (men).
• Has had major surgery prior to Study Day 1
• Has an active infection requiring systemic therapy.
• Has known hypersensitivity to the study drug or its excipients.
• Has a history of alcohol or substance abuse within 1 year prior to screening for study participation, or is currently using alcohol, drugs of abuse, or any prescribed or over-the-counter medication in a manner which, in the opinion of the Investigator, indicates abuse.
• Received treatment with another mitogen-activated protein kinase (MEK) inhibitor 8 weeks prior to Screening and throughout the treatment period of the study.
• Any of the following known active infections:
• Human immunodeficiency virus (HIV) not optimally controlled or treated. Participants with HIV who are on sustained stable antiretrovirals (for \>4 weeks) and have cluster of differentiation (CD)4+ counts ≥ 350 cells/microliter (μL) may be enrolled. No HIV testing is required unless clinically indicated or mandated by local health authority.
• Chronic hepatitis B virus (HBV) infection with surface antigen positive: participants with a prior history of treated HBV infection who are hepatitis B surface antigen-negative may be enrolled. No testing is required for hepatitis B unless clinically indicated or mandated by local health authority.
• Chronic hepatitis C virus (HCV) infection: untreated or on active treatment. Participants with a prior history of treated HCV infection who are HCV RNA-undetectable may be enrolled. No testing is required for hepatitis C unless clinically indicated or mandated by local health authority.
• Has a severe or uncontrolled medical condition (for example, dermatologic disease, etc.) that, in the opinion of the Investigator, would pose a significant clinical risk for the participant.
• Use of strong Breast Cancer Resistance Protein (BCRP) or Multidrug Resistance-Associated Protein 2 (MRP2) inhibitors within 14 days of Study Day 1 and throughout the treatment period of the study.
• Clinically significant cardiovascular disease ≤ 6 months before first dose
• Myocardial infarction or unstable angina
• Clinically significant cardiac arrhythmias
• Uncontrolled hypertension: systolic blood pressure (SBP) \> 180 millimeters of mercury (mmHg), diastolic blood pressure (DBP) \> 100 mmHg
• Pulmonary embolism, symptomatic cerebrovascular events or any other serious cardiac condition (for example, pericardial effusion or restrictive cardiomyopathy)
• QTcF prolongation \>450 msec in males and \>470 msec in females at screening or history of long QTc syndrome
• Congestive heart failure (New York Heart Association class III-IV)
• Myocarditis / clinically significant pericarditis.
• Atrial enlargement.
DRUG: REC-4881, DRUG: Placebo
Familial Adenomatous Polyposis
FAP, familial adenomatous polyposis, APC mutation, adenomatous polyposis coli, desmoid disease
UT Southwestern
A Study of TTI-101 as Monotherapy and in Combination in Participants With Locally Advanced or Metastatic, and Unresectable Hepatocellular Carcinoma
The primary objectives of Cohort A Phase 1b are to evaluate the safety and tolerability of TTI-101 orally administered as a single agent to participants with locally advanced or metastatic, and unresectable Hepatocellular Carcinoma (HCC) and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of TTI-101 as a single agent. The primary objectives of Cohort A Phase 2 are to evaluate the safety and tolerability of TTI-101 orally administered as a single agent at the RP2D to participants with locally advanced or metastatic, and unresectable HCC and to assess the preliminary efficacy of TTI-101 as a single agent in participants with locally advanced or metastatic, and unresectable HCC. The secondary objectives of Cohort A Phase 2 are to assess response, progression, survival, and pharmacokinetics. The primary objectives of Cohorts B and C Phase 1b are to evaluate the safety and tolerability of TTI-101 orally administered in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) to participants with locally advanced or metastatic, or unresectable HCC and to determine the MTD and/or RP2D of TTI-101 when used in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C). The primary objectives of Cohorts B and C Phase 2 are to evaluate the safety and tolerability of TTI-101 orally administered in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) at the RP2D to participants with locally advanced or metastatic, and unresectable HCC and to assess the preliminary efficacy of TTI-101 in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) to participants with locally advanced or metastatic, and unresectable HCC. The secondary objectives of Cohorts B and C Phase 2 are to assess response, progression, survival, and pharmacokinetics.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Hsieh
All
18 Years and over
Phase 1/Phase 2
NCT05440708
STU-2022-0622
Inclusion Criteria:
• Able to understand and willing to provide informed consent and able to comply with the study procedures and restrictions.
• Age ≥18 years at the time of informed consent.
• Have histologically or radiographically (Liver Imaging Reporting and Data Systems category 5) confirmed diagnosis of locally advanced or metastatic, and unresectable HCC. Participants without cirrhosis require histological confirmation.
• Cohorts A and B only: Willing to provide a representative fresh tumor tissue specimen prior to enrollment. The fresh tumor specimen must be obtained after progression on the prior therapy. No biopsy is required for participants in Cohort C.
• Measurable disease as per RECIST Version 1.1. Participants who received prior local therapy are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST Version 1.1.
• Able to swallow tablets.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Has adequate hematologic and organ function as defined by the following local laboratory values at screening:
• Absolute neutrophil count (ANC) ≥1.5 × 10^9/L (1500/μL) without granulocyte colony-stimulating factor support.
• Lymphocyte count ≥0.5 × 10^9/L (500/μL).
• Platelet count ≥75 × 10^9/L (75,000/μL) without transfusion.
• Hemoglobin ≥90 g/L (9 g/dL). Participants may be transfused to meet this criterion.
• Serum albumin ≥28 g/L (2.8 g/dL).
• AST, ALT, and alkaline phosphatase (ALP) ≤5 × upper limit of normal (ULN).
• Serum bilirubin ≤2 mg/dL.
• Adequate renal function defined as either:
• creatinine clearance ≥40 mL/min calculated using the Cockcroft-Gault formula, or
• 24-hour urine collection.
• Prothrombin time/international normalized ratio (PT/INR) and activated partial thromboplastin time (aPTT) ≤2 × ULN, except for participants receiving anticoagulation therapy.
• Child-Pugh class A or B7 within 7 days prior to enrollment.
• Females of childbearing potential (ie, ovulating, premenopausal, and not surgically sterile) must:
• Have a negative serum pregnancy test at screening.
• Not be breastfeeding or lactating.
• Agree to use a highly effective method of birth control for the duration of the study and for at least 30 days after the last dose in the study. Effective forms of birth control include barrier methods used in conjunction with a spermicidal agent (according to standard local practices), nonhormonal intrauterine devices, or permanent sterilization.
• Males must:
• Agree to use a condom for at least 30 days after the last dose in the study even if vasectomized in order to prevent delivery of the drug via seminal fluid.
• Agree to abstain from sperm donation through 30 days after administration of the last dose of the study treatment.
• Unless surgically sterile, males with female partners of childbearing potential must agree to use 2 methods of acceptable birth control for at least 30 days after the last dose in the study. Effective forms of birth control include barrier methods used in conjunction with a spermicidal agent (according to standard local practices), nonhormonal intrauterine devices in female partners, or permanent sterilization. Cohort A:
• In addition to the general inclusion criteria, participants enrolled in Cohort A must have demonstrated objective progression on up to 3 prior lines of systemic antitumor drug therapy. Cohort B:
• In addition to the general inclusion criteria, participants enrolled in Cohort B must have demonstrated objective progression following at least 2 cycles of first-line anti-PD-1 or anti-PD-L1 monotherapy or combination therapy. Participants may have received no more than one line of prior therapy.
• Agree to use contraception as specified in the general inclusion criteria for at least 4 months following the last dose of pembrolizumab in accordance with the approved prescribing information. Cohort C:
• In addition to the general inclusion criteria, participants enrolled in Cohort C must be naïve to systemic treatment for locally advanced or metastatic, and unresectable HCC.
• Must have had an evaluation (gastroduodenoscopy) for the presence of varices within 6 months prior to initiation of bevacizumab therapy.
• Agree to use contraception as specified in the general inclusion criteria for at least 5 months after the last dose of atezolizumab and at least 6 months after the last dose of bevacizumab in accordance with the approved prescribing information.
Exclusion Criteria:
• Pregnant or breastfeeding.
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
• History of leptomeningeal disease.
• Previous treatment of the current malignancy with a signal transducer and activator of transcription (STAT) inhibitor.
• Previous therapy with:
• Standard therapy including chemotherapy, immunotherapy, biologic therapy, or any other anticancer therapy within 28 days (or 5 elimination half-lives for non-cytotoxics, whichever is shorter) of Cycle 1 Day 1 (6 weeks for nitrosoureas or mitomycin).
• Any investigational agent within 28 days (or 5 elimination half-lives for a non-cytotoxic investigational therapy, whichever is shorter) of Cycle 1 Day 1 or 5 half-lives for a small molecule/targeted therapy.
• Extensive prior radiotherapy to more than 30% of bone marrow reserves, or prior bone marrow/stem cell transplantation within 5 years from enrollment.
• Herbal preparations are not allowed throughout the study. These herbal medications include but are not limited to St. John's wort, kava, ephedra (mahung), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. Participants should stop using herbal medications 7 days prior to the first dose of study treatment.
• Is not fully recovered from all coronavirus disease 2019 (COVID-19)-related symptoms for 2 weeks prior to Cycle 1 Day 1, if previously tested positive for COVID-19.
• Ongoing toxicity (except alopecia) due to a prior therapy, unless returned to baseline or Grade 1 or less.
• Has had major surgery within 3 weeks prior to starting investigational product (IP) or has not recovered from major side effects due to surgery.
• Significantly impaired cardiac function such as unstable angina pectoris, congestive heart failure with New York Heart Association Class III or IV, myocardial infarction within the last 12 months prior to study entry; serious arrhythmia (including QTc prolongation of >470 ms and/or pacemaker) or prior diagnosis of congenital long QT syndrome or left ventricular ejection fraction <50% on screening echocardiogram.
• Pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Participants with indwelling catheters for control of effusions or ascites are allowed.
• History of cerebrovascular accident or stroke within the previous 2 years.
• History of hepatic encephalopathy.
• Uncontrolled or symptomatic hypercalcemia (ionized calcium >1.5 mmol/L, calcium >12 mg/dL, or corrected serum calcium >ULN).
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
• History of Grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biologic composition as TTI-101 (hydroxyl-naphthalene sulfonamides).
• Known active metastases in the central nervous system (unless stable by brain imaging studies for at least 1 month without evidence of cerebral edema and no requirements for corticosteroids or anticonvulsants).
• History of difficulty swallowing oral medications, malabsorption, or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the IP.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Participants with chronic hepatitis B virus (HBV) infection, unless screening viral load <500 IU/mL on stable doses of antiviral therapy. Note: Participants with chronic hepatitis C virus (HCV) infection are allowed to enroll into the study but do not have a defined maximum viral load requirement for study entry. Participants with both HBV and HCV infection are excluded unless they have negative HCV ribonucleic acid (RNA).
• History of malignancy other than HCC within 3 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (eg, 5-year overall survival [OS] rate >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
• Has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate participation in the clinical study, or compromise compliance with the protocol such as:
• Chronic pancreatitis.
• Active untreated or uncontrolled fungal, bacterial, or viral infections (including COVID-19), sepsis, etc.
• Acute and chronic, active infectious disorders including viral and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy.
• Is unable to understand and to comply with study instructions and requirements. Cohort B: In addition to the general exclusion criteria, participants enrolled in Cohort B must fulfill the following additional exclusion criteria:
• Discontinued prior treatment with anti-PD-1 or anti-PD-L1 for any reason other than disease progression. Cohort C: In addition to the general exclusion criteria and Cohort B criteria, participants enrolled in Cohort C must fulfill the following additional exclusion criteria:
• Inadequately controlled arterial hypertension (defined as systolic blood pressure [BP] ≥150 mmHg and/or diastolic BP ≥100 mmHg), based on an average of ≥3 BP readings on ≥2 sessions.
• Participant has received prior systemic chemotherapy for locally advanced or metastatic and/or unresectable HCC. However, participant may have received either neo-adjuvant or adjuvant chemotherapy as long as it was completed at least 6 months prior to the first dose of study treatment.
• Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding and a prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment.
• Urine dipstick for proteinuria ≥2+ at screening. If a 24-hour urine collection shows <1 g of protein in 24 hours, the participant is eligible.
• Current or recent (within 10 days of first dose of study treatment) use of aspirin (>325 mg/day) or treatment with dipyridamole, ticlopidine, clopidogrel, and cilostazol.
• Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants. Prophylactic anticoagulants (eg, low-dose warfarin with target INR <1.5 × ULN or low-dose low molecular weight heparin) are allowed.
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 3 days prior to the first dose of bevacizumab.
• History of gastrointestinal perforation or evidence of abdominal free air not explained by paracentesis or recent surgical procedure.
• Metastatic disease that involves major airways or blood vessels. Participants with portal or hepatic vein involvement are not excluded.
• Participant has experienced any of the following within 6 months prior to enrollment: arterial thromboembolic event (including myocardial infarction, coronary arterial disease, transient ischemic attack, stroke, etc), congestive heart failure, hemoptysis, or pulmonary embolism.
• Participant has experienced a fistula. Cohorts B and C: In addition to the general exclusion criteria and the cohort-specific criteria listed above, participants enrolled in Cohorts B and C must fulfill the following additional exclusion criteria:
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during pembrolizumab treatment or within 5 months after the last dose of pembrolizumab treatment.
• Active or history of immune-mediated disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
• Participants with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
• Participants with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (eg, participants with psoriatic arthritis are excluded) are eligible for the study provided all of the following conditions are met:
• Rash must cover <10% of body surface area.
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids.
• No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor α [TNF-α] agents) within 2 weeks prior to initiation of study treatment. Participants receiving low-dose corticosteroids (equivalent of prednisone 10 mg/day or lower) or who receive pulse corticosteroids due to intravenous (IV) contrast allergy are not excluded.
• Active tuberculosis.
• Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Participants receiving prophylactic antibiotics (eg, to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• Prior allogeneic stem cell or solid organ transplantation.
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
Drug: TTI-101, Drug: Pembrolizumab, Drug: Atezolizumab, Drug: Bevacizumab
Hepatocellular Carcinoma, Liver
Hepatocellular carcinoma, TTI-101, Pembrolizumab, Atezolizumab, Bevacizumab, revert
UT Southwestern; Parkland Health & Hospital System
Testing the Addition of Stereotactic Radiation Therapy With Immune Therapy for the Treatment of Patients With Unresectable or Metastatic Renal Cell Cancer, SAMURAI Trial (SAMURAI)
This phase II trial tests whether the addition of radiation to the primary tumor, typically given with stereotactic ablative radiation therapy (SABR), in combination with standard of care immunotherapy improves outcomes in patients with renal cell cancer that is not recommended for surgery and has spread from where it first started (primary site) to other places in the body (metastatic). Radiation therapy uses high energy photons to kill tumor cells and shrink tumors. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses of radiation over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, avelumab, and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib, cabozantinib, and lenvatinib are in a class of medications called antiangiogenic agents. They work by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving SABR in combination with standard of care immunotherapy may help shrink or stabilize the cancer in patients with renal cell cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Raquibul Hannan
ALL
18 Years and over
PHASE2
NCT05327686
STU-2023-0448
Inclusion Criteria:
* Pathologically (histologically or cytologically) proven diagnosis of renal cell carcinoma prior to registration
* Node-positive unresectable (TxN1Mx) or metastatic (TxNxM1) based on the following diagnostic workup:
* History/physical examination within 45 days prior to registration
* CT/magnetic resonance imaging (MRI) of the chest/abdomen/pelvis within 45 days prior to registration
* Patients must have IMDC intermediate (1-2 factors) or poor risk disease (\>= 3 factors)
* 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 measurable disease (node positive or metastatic) as defined by RECIST version 1.1 excluding the primary renal tumor
* Patient not recommended for or refused immediate cytoreductive nephrectomy
* Candidate for standard of care therapy with either immuno-oncology (IO)-IO or IO-VEGF combination regimen
* Primary renal tumor measuring 20 cm or less in anterior to posterior dimension only on axial imaging
* Age \>= 18
* Karnofsky performance status \>= 60 within 45 days prior to registration
* Hemoglobin \>= 8 g/dL (transfusions are allowed) (within 45 days prior to registration)
* Platelet count \>= 50,000/mm\^3 (within 45 days prior to registration)
* Absolute neutrophil count (ANC) \>= 1500/mm\^3 (within 45 days prior to registration)
* Calculated (Calc.) creatinine clearance \>= 30 mL/min (within 45 days prior to registration)
* Creatinine clearance (CrCl) \>= 30 mL/min estimated by Cockcroft-Gault Equation
* For African American patients specifically whose renal function is not considered adequate by the formula above, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) should be used for calculating the related estimated glomerular filtration rate (GFR) with a correction factor for African American race creatinine clearance for trial eligibility, where GFR \>= 30 mL/min/1.73m\^2 will be considered adequate
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL) (within 45 days prior to registration)
* Aspartate aminotransferase and alanine aminotransferase (AST and ALT) =\< 3 x upper limit of normal (ULN) or \< 5 x ULN if hepatic metastases present (within 45 days prior to registration)
* Patients with known human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Testing is not required for entry into protocol
* 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. Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load
* The patient must agree to use a highly effective contraception, including men with vasectomies if they are having sex with a woman of childbearing potential or with a woman who is pregnant, while on study drug and for 6 months following the last dose of study drug. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
Exclusion Criteria:
* Patients with planned treatment of all metastatic disease with definitive therapy including either surgery, ablative (non-palliative) doses of radiation, or intervention of some type (definitive interventional radiology techniques) to ALL metastatic sites rendering the patient without extra-renal measurable disease. Patients NOT planned for definitive treatment of all metastatic sites are eligible. Lesions radiated palliatively are not eligible for response assessment
* Patients with untreated or unstable brain metastases or cranial epidural disease
* Note: Patients who have been adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator are eligible. Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator
* Prior radiotherapy to the kidney that would result in overlap of radiation therapy fields treatment of the primary tumor
* Any systemic therapy for metastatic renal cell carcinoma (RCC) that was initiated \> 90 days before registration, note that prior chemotherapy for a different cancer is allowed (completed \> 3 years prior to registration)
* Severe, active comorbidity defined as follows:
* Active autoimmune disease requiring ongoing therapy including systemic treatment with corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications daily. Inhaled steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
* History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies
* Active tuberculosis (purified protein derivative \[PPD\] response without active tuberculosis \[TB\] is allowed)
* Uncontrolled hypertension (systolic blood pressure \[BP\] \>= 190 mmHg or diastolic BP \> 110 mmHg)
* Major surgery requiring hospital admission =\< 28 days prior to registration
* Any serious (requiring hospital stay or long term rehab) non-healing wound, ulcer, or bone fracture within 45 days prior to registration
* Any arterial thrombotic (ST elevation myocardial infarction \[STEMI\], non-ST elevation myocardial infarction \[NSTEMI\], cerebrovascular accident \[CVA\], etc) events within 180 days prior to registration
* Active New York (NY) Heart Association class 3-4 heart failure symptoms
* Moderate or severe hepatic impairment (Child-Pugh B or C)
* Any history of untreated pulmonary embolism or deep venous thrombosis (DVT) within 180 days prior to registration. (Any asymptomatic or treated pulmonary embolism or asymptomatic treated deep venous thrombosis \> 30 days prior to registration is allowed)
* Unstable cardiac arrhythmia within 180 days prior to registration
* History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior to registration
* History of or active inflammatory bowel disease
* Malabsorption syndrome within 45 days prior to registration
* Pregnancy and individuals unwilling to discontinue nursing. For women of child bearing potential must have a negative pregnancy test =\< 45 days prior to registration BIOLOGICAL: Avelumab, DRUG: Axitinib, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, DRUG: Cabozantinib, PROCEDURE: Computed Tomography, BIOLOGICAL: Ipilimumab, DRUG: Lenvatinib, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Nivolumab, BIOLOGICAL: Pembrolizumab, RADIATION: Stereotactic Ablative Radiotherapy
Metastatic Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Unresectable Renal Cell Carcinoma, Kidney
UT Southwestern; Parkland Health & Hospital System
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
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 Stage IIB, IIC, or Stage III colon adenocarcinoma with R0 resection according to AJCC 8th edition criteria.
No radiographic evidence of overt metastatic disease within 45 days prior to Step 1/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 IIB, IIC, or Stage III colon cancer must have central testing for ctDNA using the Signatera™ assay by Natera (after Step 1/Study entry and before Step2/Randomization). Patient must have sufficient tissue to meet protocol requirements. This blood specimen for the Signatera assay must be collected after surgery (and recommended at least 14 days post surgery).
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 Step 1/Study entry must be no more than 60 days. NOTE: Step 1/Study Entry may occur as early as post operative Day 7, but it cannot occur beyond 60 days from the actual date of the patient's surgery.
Availability and provision of adequate surgical tumor tissue for molecular diagnostics and confirmatory profiling.
Adequate hematologic function within 28 days before Step 1/Study entry defined as follows:
* Absolute neutrophil count (ANC) must be greater than or equal to 1500/mm3;
* Participants with benign ethnic neutropenia (BEN): ANC less than 1300 mm3 are eligible.
* BEN (also known as constitutional neutropenia) is an inherited cause of mild or moderate neutropenia that is not associated with any increased risk for infections or other clinical manifestations. BEN is referred to as ethnic neutropenia because of its increased prevalence in people of African descent and other specific ethnic groups.
* 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 Step 1/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 Step 1/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) NOTE: Adjusted body weight (AdjBW) should be used for patients that have BMI greater than or equal to 28 (less than or equal to 30% above IBW).
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 Step 1/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 second randomization must be negative (for women of childbearing potential only).
Adequate hematologic function within 28 days before second randomization defined as follows:
* Absolute neutrophil count (ANC) must be greater than or equal to 1500/mm3;
* Participants with benign ethnic neutropenia (BEN): ANC less than 1300 mm3 are eligible.
* BEN (also known as constitutional neutropenia) is an inherited cause of mild or moderate neutropenia that is not associated with any increased risk for infections or other clinical manifestations. BEN is referred to as ethnic neutropenia because of its increased prevalence in people of African descent and other specific ethnic groups.
* 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 second 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 second 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). EXCEPTION: one cycle of chemotherapy (regimen per treating physicians' discretion - 5-FU or capecitabine with or without oxaliplatin) is allowed but not required after consent. The optional cycle of chemotherapy should be started greater than or equal to 4 weeks from surgery and while awaiting Step 2 randomization.
Other invasive malignancy within 5 years before Step 1/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 Step 1/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, Colon, Rectum
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
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
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
Liver Fibroses, Cirrhosis, Liver
Liver Disease, Chemoprevention, HCC, Atorvastatin
UT Southwestern
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, Evelyn.Rojo@UTSouthwestern.edu
Norberto Rodriguez-Baez
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 normalization ratio (INR) of ≥ 1.5 or \< 2.0 (not corrected by vitamin K) with evidence of hepatic encephalopathy (HE), INR of ≥ 1.5 or \< 2.0 for at least 7 days duration without evidence of 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
• Patients with positive respiratory secretion testing for respiratory viral infection including SARS-CoV-2, influenza and respiratory syncytial virus only if they also have declining respiratory function
• 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
Acute Liver Failure, Fulminant Hepatic Failure, Hepatic Encephalopathy, Acute Liver Injury, Immune Dysregulation, Liver
hepatic insufficiency, liver diseases, liver failure, anti-thymocyte agents
Children’s Health
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
ALL
18 Years and over
PHASE3
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 Clear Cell Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma, Stage IV Renal Cell Cancer AJCC v8, Kidney
UT Southwestern
A Phase 1/2, Open-label, Safety and Dosing Study of Autologous CART Cells (Desmoglein 3 Chimeric Autoantibody Receptor T Cells [DSG3-CAART] or CD19-specific Chimeric Antigen Receptor T Cells [CABA-201]) in Subjects With Active, Pemphigus Vulgaris (RESET-PV)
A phase 1/2, open-label, safety and dosing study of autologous CART cells (desmoglein 3 chimeric autoantibody receptor T cells \[DSG3-CAART\] or CD19-specific Chimeric Antigen Receptor T cells \[CABA-201\]) in subjects with active, pemphigus vulgaris
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Arturo Dominguez
ALL
18 Years and over
PHASE1
NCT04422912
STU-2021-0086
Inclusion Criteria for DSG3-CAART: Closed to enrollment
* Confirmed diagnosis of mPV by prior or screening biopsy and prior positive anti- DSG3 antibody ELISA
* mPV inadequately managed by at least one standard immunosuppressive therapies
* Active mPV at screening
* Anti-DSG3 antibody ELISA positive at screening
Inclusion Criteria for CABA-201 sub-study: Open to enrollment
* Age ≥18
* Confirmed diagnosis of PV by prior or screening biopsy and prior positive DSG3 ELISA, IIF, and/or DIF
* PV inadequately managed by at least one standard immunosuppressive therapy
* Active PV at screening
* DSG3 ELISA positive at screening
Exclusion Criteria:
* Active cutaneous lesions associated with PV that indicates mucocutaneous rather than mucosal-dominant disease
* Rituximab in last 12 months unless PV symptoms have recently worsened or anti-DSG3 antibody titers have recently increased
* Prednisone \> 0.25mg/kg/day
* Other autoimmune disorder requiring immunosuppressive therapies
* Investigational treatment in last 3 months
Exclusion Criteria for CABA-201 sub-study
* Have paraneoplastic pemphigus or active malignancy (not including non-melanoma skin cancer) or malignancy diagnosed within the previous 5 years
* Have received rituximab or other anti-CD20 or anti-CD19 therapies in last 12 months unless anti-DSG3 antibody titers have recently increased or PV symptoms have recently worsened
* Prednisone \> 0.25mg/kg/day
* Other autoimmune disorder requiring immunosuppressive therapies
* Treatment with any investigational agent within 4 weeks or 5 half-lives, whichever is longer. BIOLOGICAL: DSG3-CAART, BIOLOGICAL: CABA-201
Pemphigus Vulgaris, Esophagus, Lip, Oral Cavity and Pharynx, Other Skin, Rectum
Pemphigus, Pemphigus Vulgaris, CAAR-T Therapy, CAR-T Therapy, Desmoglein 3, Cell Therapy, Autoimmune Disease, Autoimmunity, Skin Diseases, Vesiculobullous, Immunotherapy, Adoptive, Immune System Diseases, CABA-201, Anti-CD19 CAR-T therapy, Resecabtagene Autoleucel, Rese-cel
UT Southwestern
Cobimetinib in Refractory Langerhans Cell Histiocytosis (LCH), and Other Histiocytic Disorders (NACHO-COBI)
This is a research study of a drug called cobimetinib in children and adults diagnosed with Langerhans cell histiocytosis (LCH), and other histiocytic disorders that has returned or does not respond to treatment. Cobimetinib blocks activation of a protein called Mitogen-activated protein kinase (MEK) that is part of incorrect growth signals in histiocytosis cells. Four different groups of patients will be enrolled.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Erin Butler
All
Not specified
Phase 2
NCT04079179
STU-2021-0830
INCLUSION CRITERIA:
Age at study entry
• For Group 1: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 2: Participant may be at least 6 months of age at the time of enrollment
• For Group 3: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 4: Participant must be 21 years of age or older at the time of enrollment
• Participant must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet which may be taken by mouth or other enteral route such as nasogastric or gastric tube.
• Biopsy proven LCH -AND
• Failure of at least front-line therapy for LCH with evaluable disease. -OR
• Diagnosis of LCH-associated neurodegenerative disease with radiologic or clinical progression within the past 3 months. -OR
• Biopsy proven JXG, ECD, RDD, histiocytic sarcoma, or other histiocytic lesion (newly diagnosed or relapsed/refractory disease) with evaluable active disease. Performance Level: -Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age. Adequate Hematologic Function Defined as:
• ANC ≥ 0.75 x 10^9/L (unsupported/without growth factor stimulant)
• Platelet count ≥ 75 x 10^9/L (unsupported/without transfusion within the past 7 days).
• Patients with marrow disease must have platelet count of >/= 75 x 10^9/L (transfusion support allowed) and must not be refractory to platelet transfusions.
• Hemoglobin ≥ 8 g/dL (unsupported/without transfusion within the past 7 days)
• Patients with marrow disease must have hemoglobin ≥ 8 g/dL (transfusion support allowed). Adequate Renal Function Defined as:
• Calculated creatinine clearance (or radioisotope GFR) ≥ 70 mL/min/1.73m^2 or serum creatinine based on age/gender as follows: Maximum Serum Creatinine (mg/dL) Age 2 to < 6 years: Male 0.8 mg/d, Female 0.8; 6 to < 10 years: Male 1 mg/dL,Female 1; 10 to < 13 years: Male 1.2 mg/dL; Female 1.2; 13 to < 16 years: Male 1.5 mg/dL ; Female 1.4; ≥ 16 years: Male 1.7 mg/dL; Female 1.4; Adequate Liver Function Defined as:
• Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
• AST and ALT ≤ 3x ULN (≤ 5 x ULN for participants with liver involvement)
• Serum albumin ≥ 2 g/dL. For patients with liver disease caused by histiocytic disorder: • Patients may be enrolled with abnormal bilirubin, AST, ALT and albumin with documentation of histiocytic liver disease. Adequate Cardiac Function Defined as:
• Fractional shortening (FS) of ≥ 30% or ejection fraction of ≥ 50% by echocardiogram at baseline, as determined by echocardiography or multigated acquisition scan (MUGA) within 28 days prior to enrollment. Depending on institutional standard, either FS or LVEF is adequate for enrollment if only one value is measured; if both values are measured, then both values must meet criteria above Pregnancy/Birth Control
• Female patients of childbearing potential require a negative urine or serum pregnancy test for eligibility and again at database registration, if more than 2 weeks has elapsed.
• Female patients of childbearing potential must agree to follow the contraceptive requirements using two forms of effective contraceptive methods for the duration of the study treatment. Male patients with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) must agree to use two forms of effective methods of contraception (one of which must be a barrier method) during the treatment period and for at least 3 months after the last dose of the study drug to avoid pregnancy and/or potential adverse effects on a developing embryo. Agreement to true abstinence (not periodic abstinence or withdrawal method) is an acceptable method of birth control. EXCLUSION CRITERIA:
• Prior and Concomitant Use of Drugs with CYP3A4 inducing/inhibiting activity: Patient taking strong inducers or inhibitors of CYP3A4 within 14 days prior to study enrollment, including but not limited to the following: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort.
• Prior Therapy Restrictions Completion of previous chemotherapy, immunotherapy, radiotherapy, or targeted therapy for LCH (or other histiocytic disorder) at least 28 days (except where specified below) prior to study enrollment, with resolution of all associated toxicity to ≤ Grade 1 prior to study enrollment (exception for alopecia and ototoxicity which do not need to be resolved ≤ Grade 1). 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 laboratory eligibility criteria are met, the patient is considered to have recovered adequately.
• Radiation therapy within the 28 days prior to enrollment.
• Any prior treatment with Cobimetinib.
• Treatment with a long-acting hematopoietic growth factor within 14 days prior to initiation of study drug or a short-acting hematopoietic growth factor within 7 days prior to enrollment.
• Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives), immunotherapy, biologic therapy, investigational therapy, or herbal cancer therapy within 28 days or < 5 half-lives, whichever is longer, prior to study enrollment.
• Treatment with high-dose chemotherapy and stem-cell rescue (autologous stem cell transplant) or allogeneic stem cell transplant within 90 days prior to enrollment. 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.
• For patients with brain tumors (intracranial masses), use of anticoagulants within 7 days prior to enrollment.
• Corticosteroid therapy <0.5 mg/kg/day averaged during the month prior to study enrollment is permissible but must be discontinued fourteen (14) days prior to enrollment. Patients with documented brain lesions receiving corticosteroids for management of cerebral edema must be on a stable dose for fourteen (14) days prior to enrollment.
• Patient has received treatment with investigational therapy within 4 weeks prior to initiation of study drug.
• Patients taking anticoagulants or have a pre-existing bleeding disorder unrelated to histiocytic disease.
• Exclusions for other illness
• Other active malignancy or history of secondary malignancy.
• Refractory nausea and vomiting, malabsorption, external biliary shunt
• Infection: Patients who have a known active infection (excluding documented fungal infection of the nail beds) within 28 days prior to enrollment that has not completely resolved.
• Major surgical procedure or significant traumatic injury within 28 days prior to enrollment, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within fourteen (14) days prior to study enrollment (provided that the wound has healed).
• History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease.
• History of pneumonitis.
• Ophthalmologic considerations: Patients with known significant ophthalmologic conditions or known risk factors for retinal vein occlusion are not eligible. Specifically, patients with a history of retinal vein occlusion (RVO), retinal detachment, retinal pathology on ophthalmologic exam, retinopathy of prematurity, central serous chorioretinopathy (CSSCR), neovascular retinopathy, intraocular pressure > 21 mmHg, and predisposing factors to RVO (e.g., uncontrolled hypertension, diabetes, or hyperlipidemia, coagulopathy) will be excluded. Patients with longstanding and stable ophthalmologic findings secondary to existing conditions are eligible with appropriate written documentation and approval from Study Chair.
• History of solid organ transplantation: Patients who have received a prior solid organ transplantation are not eligible.
• Any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that in the opinion of the investigator contraindicates use of an investigational drug or places the patient at unacceptable risk from treatment complications.
• History of clinically significant cardiac dysfunction, including the following:
• Clinically significant cardiac arrhythmias including brady-arrhythmias and/or patients who require anti-arrhythmic therapy (with the exception of beta blockers or digoxin). Patients with controlled atrial fibrillation are not excluded.
• Unstable arrhythmia
• Unstable angina, or new-onset angina within 3 months prior to initiation of study treatment
• Symptomatic congestive heart failure, defined as New York Heart Association Class II or higher
• Myocardial infarction within 3 months prior to initiation of study treatment
• Known chronic human immunodeficiency virus (HIV).
• History of Grade ≥ 2 CNS hemorrhage or history of any CNS hemorrhage within 28 days of enrollment.
• Female patients who are pregnant or lactating. Pregnant or lactating women will not be entered on this study because there is no available information regarding human fetal or teratogenic toxicities.
• For Group 1: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 2: Participant may be at least 6 months of age at the time of enrollment
• For Group 3: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 4: Participant must be 21 years of age or older at the time of enrollment
• Participant must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet which may be taken by mouth or other enteral route such as nasogastric or gastric tube.
• Biopsy proven LCH -AND
• Failure of at least front-line therapy for LCH with evaluable disease. -OR
• Diagnosis of LCH-associated neurodegenerative disease with radiologic or clinical progression within the past 3 months. -OR
• Biopsy proven JXG, ECD, RDD, histiocytic sarcoma, or other histiocytic lesion (newly diagnosed or relapsed/refractory disease) with evaluable active disease. Performance Level: -Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age. Adequate Hematologic Function Defined as:
• ANC ≥ 0.75 x 10^9/L (unsupported/without growth factor stimulant)
• Platelet count ≥ 75 x 10^9/L (unsupported/without transfusion within the past 7 days).
• Patients with marrow disease must have platelet count of >/= 75 x 10^9/L (transfusion support allowed) and must not be refractory to platelet transfusions.
• Hemoglobin ≥ 8 g/dL (unsupported/without transfusion within the past 7 days)
• Patients with marrow disease must have hemoglobin ≥ 8 g/dL (transfusion support allowed). Adequate Renal Function Defined as:
• Calculated creatinine clearance (or radioisotope GFR) ≥ 70 mL/min/1.73m^2 or serum creatinine based on age/gender as follows: Maximum Serum Creatinine (mg/dL) Age 2 to < 6 years: Male 0.8 mg/d, Female 0.8; 6 to < 10 years: Male 1 mg/dL,Female 1; 10 to < 13 years: Male 1.2 mg/dL; Female 1.2; 13 to < 16 years: Male 1.5 mg/dL ; Female 1.4; ≥ 16 years: Male 1.7 mg/dL; Female 1.4; Adequate Liver Function Defined as:
• Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
• AST and ALT ≤ 3x ULN (≤ 5 x ULN for participants with liver involvement)
• Serum albumin ≥ 2 g/dL. For patients with liver disease caused by histiocytic disorder: • Patients may be enrolled with abnormal bilirubin, AST, ALT and albumin with documentation of histiocytic liver disease. Adequate Cardiac Function Defined as:
• Fractional shortening (FS) of ≥ 30% or ejection fraction of ≥ 50% by echocardiogram at baseline, as determined by echocardiography or multigated acquisition scan (MUGA) within 28 days prior to enrollment. Depending on institutional standard, either FS or LVEF is adequate for enrollment if only one value is measured; if both values are measured, then both values must meet criteria above Pregnancy/Birth Control
• Female patients of childbearing potential require a negative urine or serum pregnancy test for eligibility and again at database registration, if more than 2 weeks has elapsed.
• Female patients of childbearing potential must agree to follow the contraceptive requirements using two forms of effective contraceptive methods for the duration of the study treatment. Male patients with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) must agree to use two forms of effective methods of contraception (one of which must be a barrier method) during the treatment period and for at least 3 months after the last dose of the study drug to avoid pregnancy and/or potential adverse effects on a developing embryo. Agreement to true abstinence (not periodic abstinence or withdrawal method) is an acceptable method of birth control. EXCLUSION CRITERIA:
• Prior and Concomitant Use of Drugs with CYP3A4 inducing/inhibiting activity: Patient taking strong inducers or inhibitors of CYP3A4 within 14 days prior to study enrollment, including but not limited to the following: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort.
• Prior Therapy Restrictions Completion of previous chemotherapy, immunotherapy, radiotherapy, or targeted therapy for LCH (or other histiocytic disorder) at least 28 days (except where specified below) prior to study enrollment, with resolution of all associated toxicity to ≤ Grade 1 prior to study enrollment (exception for alopecia and ototoxicity which do not need to be resolved ≤ Grade 1). 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 laboratory eligibility criteria are met, the patient is considered to have recovered adequately.
• Radiation therapy within the 28 days prior to enrollment.
• Any prior treatment with Cobimetinib.
• Treatment with a long-acting hematopoietic growth factor within 14 days prior to initiation of study drug or a short-acting hematopoietic growth factor within 7 days prior to enrollment.
• Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives), immunotherapy, biologic therapy, investigational therapy, or herbal cancer therapy within 28 days or < 5 half-lives, whichever is longer, prior to study enrollment.
• Treatment with high-dose chemotherapy and stem-cell rescue (autologous stem cell transplant) or allogeneic stem cell transplant within 90 days prior to enrollment. 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.
• For patients with brain tumors (intracranial masses), use of anticoagulants within 7 days prior to enrollment.
• Corticosteroid therapy <0.5 mg/kg/day averaged during the month prior to study enrollment is permissible but must be discontinued fourteen (14) days prior to enrollment. Patients with documented brain lesions receiving corticosteroids for management of cerebral edema must be on a stable dose for fourteen (14) days prior to enrollment.
• Patient has received treatment with investigational therapy within 4 weeks prior to initiation of study drug.
• Patients taking anticoagulants or have a pre-existing bleeding disorder unrelated to histiocytic disease.
• Exclusions for other illness
• Other active malignancy or history of secondary malignancy.
• Refractory nausea and vomiting, malabsorption, external biliary shunt
• Infection: Patients who have a known active infection (excluding documented fungal infection of the nail beds) within 28 days prior to enrollment that has not completely resolved.
• Major surgical procedure or significant traumatic injury within 28 days prior to enrollment, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within fourteen (14) days prior to study enrollment (provided that the wound has healed).
• History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease.
• History of pneumonitis.
• Ophthalmologic considerations: Patients with known significant ophthalmologic conditions or known risk factors for retinal vein occlusion are not eligible. Specifically, patients with a history of retinal vein occlusion (RVO), retinal detachment, retinal pathology on ophthalmologic exam, retinopathy of prematurity, central serous chorioretinopathy (CSSCR), neovascular retinopathy, intraocular pressure > 21 mmHg, and predisposing factors to RVO (e.g., uncontrolled hypertension, diabetes, or hyperlipidemia, coagulopathy) will be excluded. Patients with longstanding and stable ophthalmologic findings secondary to existing conditions are eligible with appropriate written documentation and approval from Study Chair.
• History of solid organ transplantation: Patients who have received a prior solid organ transplantation are not eligible.
• Any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that in the opinion of the investigator contraindicates use of an investigational drug or places the patient at unacceptable risk from treatment complications.
• History of clinically significant cardiac dysfunction, including the following:
• Clinically significant cardiac arrhythmias including brady-arrhythmias and/or patients who require anti-arrhythmic therapy (with the exception of beta blockers or digoxin). Patients with controlled atrial fibrillation are not excluded.
• Unstable arrhythmia
• Unstable angina, or new-onset angina within 3 months prior to initiation of study treatment
• Symptomatic congestive heart failure, defined as New York Heart Association Class II or higher
• Myocardial infarction within 3 months prior to initiation of study treatment
• Known chronic human immunodeficiency virus (HIV).
• History of Grade ≥ 2 CNS hemorrhage or history of any CNS hemorrhage within 28 days of enrollment.
• Female patients who are pregnant or lactating. Pregnant or lactating women will not be entered on this study because there is no available information regarding human fetal or teratogenic toxicities.
Drug: Cobimetinib
Langerhan's Cell Histiocytosis, Juvenile Xanthogranuloma, Erdheim-Chester Disease, Rosai Dorfman Disease, Neuro-Degenerative Disease, Histiocytic Sarcoma, Histiocytic Disorders, Malignant, Bones and Joints, Brain and Nervous System, Liver, Lung/Thoracic, Other Hematopoietic
Cobimetinib, Langerhans Cell Histiocytosis (LCH)
Children’s Health
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, Alyssa.Aguas@UTSouthwestern.edu
Samir Pandya
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, Tracheoesophageal Fistula, Esophagus
Children’s Health