Recruiting
Phase 1

Trifluridine/Tipiracil & Talazoparib

Sponsor:

Roswell Park Cancer Institute

Code:

NCT04511039

Conditions

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

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Trifluridine and Tipiracil Hydrochloride

Talazoparib Tosylate

Study Details

Brief 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.

Conditions

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

Study ID

NCT04511039

Start date

Jun 8, 2021

Status verified date

Apr, 2026

Completion date

Apr 1, 2029

Anticipated

Primary completion date

Sep 1, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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, 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

Study Design

Enrollment

45 participants

Anticipated

Allocation

Non randomized

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment Arm

Patients receive trifluridine/tipiracil PO BID and talazoparib tosylate PO QD on days 1-5. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Interventions

Trifluridine and Tipiracil Hydrochloride

Given PO

Talazoparib Tosylate

Given PO

Primary outcome measure

  • Incidence of Adverse Events [ Time Frame: after each cycle of treatment ( 1 cycle = 14 days) ]
  • Maximum tolerated dose/ recommended phase II dose [ Time Frame: Up to 14 days ]

Central Contacts and Locations

Central contacts

Sarah Chatley, BS

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

Locations

Roswell Park Cancer Institute

Recruiting

Buffalo, New York, United States, 14263

More Information

Sponsor

Roswell Park Cancer Institute

Last update posted

May 4, 2026

Last verified

Apr, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Roswell Park Cancer Institute on 2026-05-04.