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

Recruiting now · Phase 1

Conditions studied: Advanced Malignant Solid Neoplasm, Clinical Stage III Gastroesophageal Junction Adenocarcinoma, Clinical Stage IV Gastroesophageal Junction Adenocarcinoma, Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma, Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma A, Locally Advanced Colorectal Carcinoma, Locally Advanced Gastroesophageal Junction Adenocarcinoma, Metastatic Colorectal Adenocarcinoma, Metastatic Gastroesophageal Junction Adenocarcinoma, Pathologic Stage III Gastroesophageal Junction Adenocarcinoma, Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma, Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma, Pathologic Stage IV Gastroesophageal Junction Adenocarcinoma, Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma, Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma, Postneoadjuvant Therapy Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8, Postneoadjuvant Therapy Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8, Postneoadjuvant Therapy Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8, Postneoadjuvant Therapy Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8, Postneoadjuvant Therapy Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8, Postneoadjuvant Therapy Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8, Stage III Colorectal Cancer AJCC v8, Stage IIIA Colorectal Cancer AJCC v8, Stage IIIB Colorectal Cancer AJCC v8, Stage IIIC Colorectal Cancer AJCC v8, Stage IV Colorectal Cancer AJCC v8, Stage IVA Colorectal Cancer AJCC v8, Stage IVB Colorectal Cancer AJCC v8, Stage IVC Colorectal Cancer AJCC v8

In brief

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.

Key facts

Study ID: NCT04511039
Run by: Roswell Park Cancer Institute
People needed: 45
Starts: 2021-06-08
Expected to finish: 2029-04-01
Last updated by the study team: 2026-05-04

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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

You may not qualify if…

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, FUDR 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

Where it is running

Roswell Park Cancer Institute — Buffalo, New York, United States (enrolling)

Full record on ClinicalTrials.gov

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