Esophageal Cancer Clinical Trial
Trifluridine/Tipiracil and Talazoparib for the Treatment of Patients With Locally Advanced or Metastatic Colorectal or Gastroesophageal Cancer
This phase I trial investigates the side effects and best dose of talazoparib when given together with trifluridine/tipiracil for the treatment of patients with colorectal or gastroesophageal cancer that has spread to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic). Drugs used in the chemotherapy, such as trifluridine/tipiracil, 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. Talazoparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving talazoparib with trifluridine/ tipiracil may inhibit certain enzymes in the cells that are responsible for tumor cell growth.
I. To determine the safety, maximum tolerated dose (MTD), and recommended phase 2 dose (RP2D) of trifluridine and tipiracil hydrochloride (trifluridine/tipiracil [FTD/TPI]) in combination with talazoparib tosylate (talazoparib) in patients with advanced colorectal (CRC) or gastroesophageal (EGC) adenocarcinoma.
Histologically or cytologically confirmed CRC or EGC adenocarcinoma that is locally advanced or metastatic
Has received at least one prior line of therapy with progression or intolerance
Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Life expectancy >= 3 months by investigator assessment
Hemoglobin >= 9 g/dL
Absolute neutrophil count >= 1500/mm^3
Platelet count >= 100,000/mm^3 without transfusion or growth factor support
Creatinine < 1.5 upper limit of normal (ULN) or creatinine clearance > 60 mL/min
Total bilirubin < 1.5 x ULN
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN or < x 5 ULN in the presence of liver metastasis
Albumin > 3 g/dL
Ability to swallow oral medications
Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
Systemic antineoplastic therapy within 2 weeks prior to initiation of FTD/TPI run-in phase (within the past 6 weeks if this treatment is mitomycin C or nitrosourea)
Radiotherapy within the past 2 weeks excluding palliative radiotherapy to painful bone lesions
Prior treatment with PARP inhibitor or FTD/TPI
Any condition that in the investigator's opinion can limit absorption of FTD/TPI or talazoparib from the gastrointestinal (GI) tract
Gastrointestinal obstruction (without diversion) or perforation within 4 weeks from initiation of FTD/TPI run-in
Refractory ascites (requiring weekly or more frequent paracentesis or permanent indwelling peritoneal catheter)
Untreated central nervous system (CNS) disease. Patients with leptomeningeal disease are ineligible but patients with treated, stable CNS metastasis for at least 4 weeks are allowed to participate
Significant cardiac disease defined as congestive heart failure stage III or IV (New York Heart Association [NYHA]), acute coronary event, cerebrovascular event, peripheral arterial embolic event, venous thromboembolic event (pulmonary embolism or lower extremity deep vein thrombosis), or ventricular arrhythmia within the past 3 months
Other malignancy requiring active therapy
Presence of toxicities from prior therapy of grade 2 or higher
Active infection requiring antibiotic therapy
Known human immunodeficiency virus (HIV) or hepatitis B infection or untreated hepatitis C infection. Patients with treated hepatitis C infection and undetectable viral load are allowed to participate
Any history of myelodysplastic syndrome, acute leukemia, or bone marrow transplant
Pregnant or nursing female participants
Unwilling or unable to follow protocol requirements
Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug
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