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RECRUITINGPHASE1

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

A Phase I Study of Trifluridine/ Tipiracil Plus the Poly (ADP) Ribose Polymerase Inhibitor Talazoparib in Advanced Cancers

NCT04511039•Roswell Park Cancer Institute

View on ClinicalTrials.gov

Summary

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.

Detailed Description

PRIMARY OBJECTIVE: 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. SECONDARY OBJECTIVES: I. To determine the pharmacokinetics (PK) and pharmacodynamic (PD) markers of activity. II. To evaluate the preliminary antineoplastic efficacy of the combination.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

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
+5 more criteria

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, 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
+6 more criteria

Locations (1)

Roswell Park Cancer Institute

Buffalo, New York, United States

Key Dates

Start Date

June 8, 2021

Primary Completion Date

September 1, 2026

Completion Date

April 1, 2027

Last Updated

March 2, 2026

Enrollment

ESTIMATED participants

Conditions

Advanced Malignant Solid NeoplasmClinical Stage III Gastroesophageal Junction AdenocarcinomaClinical Stage IV Gastroesophageal Junction AdenocarcinomaClinical Stage IVA Gastroesophageal Junction AdenocarcinomaClinical Stage IVB Gastroesophageal Junction Adenocarcinoma ALocally Advanced Colorectal CarcinomaLocally Advanced Gastroesophageal Junction AdenocarcinomaMetastatic Colorectal AdenocarcinomaMetastatic Gastroesophageal Junction AdenocarcinomaPathologic Stage III Gastroesophageal Junction AdenocarcinomaPathologic Stage IIIA Gastroesophageal Junction AdenocarcinomaPathologic Stage IIIB Gastroesophageal Junction AdenocarcinomaPathologic Stage IV Gastroesophageal Junction AdenocarcinomaPathologic Stage IVA Gastroesophageal Junction AdenocarcinomaPathologic Stage IVB Gastroesophageal Junction AdenocarcinomaPostneoadjuvant Therapy Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8Postneoadjuvant Therapy Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8Postneoadjuvant Therapy Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8Postneoadjuvant Therapy Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8Postneoadjuvant Therapy Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8Postneoadjuvant Therapy Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8Stage III Colorectal Cancer AJCC v8Stage IIIA Colorectal Cancer AJCC v8Stage IIIB Colorectal Cancer AJCC v8Stage IIIC Colorectal Cancer AJCC v8Stage IV Colorectal Cancer AJCC v8Stage IVA Colorectal Cancer AJCC v8Stage IVB Colorectal Cancer AJCC v8Stage IVC Colorectal Cancer AJCC v8

Interventions

Trifluridine and Tipiracil Hydrochloride

DRUG

Talazoparib Tosylate

DRUG

Contacts

Sarah Chatley, BS

CONTACT

716-845-4846 Sarah.Chatley@roswellpark.org

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 2, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

Personalized Antibody-Drug Conjugate Therapy Based on RNA and Protein Testing for the Treatment of Advanced or Metastatic Solid Tumors (The ADC MATCH Screening and Treatment Trial)

Testing A New Anti-cancer Drug Combination, Entinostat and ZEN003694, for Advanced and Refractory Solid Tumors

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Testing the Combination of Two Anti-cancer Drugs, DS-8201a and AZD6738, for The Treatment of Advanced Solid Tumors Expressing the HER2 Protein or Gene, The DASH Trial

Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations

Talazoparib and Palbociclib, Axitinib, or Crizotinib for the Treatment of Advanced or Metastatic Solid Tumors, TalaCom Trial