A Phase I Study of Trifluridine/ Tipiracil Plus the Poly (ADP) Ribose Polymerase Inhibitor Talazoparib in Advanced Cancers
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.
• Histologically or cytologically confirmed CRC or EGC adenocarcinoma that is locally advanced or metastatic (Cohort A); histologically or cytologically confirmed p53mt/RASonc (Cohort B1) or p53mt/RASwt CRC (Cohort B2) that is locally advanced or metastatic. Patients with adenocarcinoma histology only are allowed to participate.
• 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