Trifluridine/Tipiracil and Talazoparib for the Treatment of Patients With Locally Advanced or Metastatic Colorectal or Gastroesophageal Cancer

Launched by ROSWELL PARK CANCER INSTITUTE · Aug 10, 2020

Keywords

ClinConnect Summary

This clinical trial is studying the combination of two cancer treatments, trifluridine/tipiracil and talazoparib, to see how well they work together for patients with advanced colorectal or gastroesophageal cancer. These cancers can be locally advanced, meaning they have spread to nearby tissue or lymph nodes, or metastatic, meaning they have spread to other parts of the body. The goal is to find the best dose of talazoparib and to understand any side effects that might occur when it's given with trifluridine/tipiracil.

To be eligible for this trial, participants need to have a confirmed diagnosis of colorectal or gastroesophageal cancer that is advanced or has not responded well to previous treatments. They should also be generally healthy, with a good performance status, and have certain blood counts within normal ranges. Participants can expect to take the medications orally and will be closely monitored for their health and any side effects throughout the study. It's important to note that women who can become pregnant will need to use effective birth control during the trial and inform their doctor if they become pregnant. This trial is currently recruiting participants.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 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
• Exclusion Criteria:
• • Systemic antineoplastic therapy within 2 weeks prior to day -14 (Dose Escalation, Cohort A) or Cycle 1 day 1 (Dose Expansion, Cohorts B1 and B2) or 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 day -14 (Dose Escalation, Cohort A) or Cycle 1 Day 1 (Dose Expansion, Cohorts B1 and B2.
• • 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