A Phase I Study of Trifluridine/ Tipiracil Plus the Poly (ADP) Ribose Polymerase Inhibitor Talazoparib in Advanced Cancers
Roswell Park Cancer Institute
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.
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 range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
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) performan…
Interventions
- DrugTrifluridine and Tipiracil Hydrochloride
Given PO
- DrugTalazoparib Tosylate
Given PO
Location
- Roswell Park Cancer InstituteBuffalo, New York