Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Carcinoma

Adenocarcinoma

Colorectal Neoplasms

Esophageal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Head and Neck Neoplasms

Esophageal Diseases

Esophageal Cancer

Anti-Infective Agents

All Drugs and Chemicals

Antineoplastic Agents

Trifluridine

Talazoparib

Antimetabolites

Antiviral Agents

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

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.

Trifluridine and Tipiracil Hydrochloride

Talazoparib Tosylate

Christos Fountzilas, MD

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.

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.

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

All adverse events will be evaluated using Common Terminology Criteria for All Adverse Events (CTCAE) version (v.) 5.

Will utilize the keyboard design - a novel model- assisted dose-finding method to find the maximum tolerated dose

The pharmacokinetic parameters between Trifluridine/Tipiracil and Talazoparib will be evaluated on Day -14: pre-dose, 0.5, 1, 2, 4, 6, 8 hours (hr) post-dose; day-13: 24 hr post-initial dose and day -13 pre-dose

Will be summarized using frequencies and relative frequencies.

ill be summarized using frequencies and relative frequencies. .

Will be summarized using standard Kaplan-Meier methods

Tumor biopsies will be summarized by dose level and time-point using means and standard deviations.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Trifluridine/Tipiracil and Talazoparib for the Treatment of Patients With Locally Advanced or Metastatic Colorectal or Gastroesophageal Cancer	NCT04511039	Advanced Malign... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Locally Advance... Locally Advance... Metastatic Colo... Metastatic Gast... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Stage III Color... Stage IIIA Colo... Stage IIIB Colo... Stage IIIC Colo... Stage IV Colore... Stage IVA Color... Stage IVB Color... Stage IVC Color...	Trifluridine an... Talazoparib Tos...	18 Years -	Roswell Park Cancer Institute
Trifluridine/Tipiracil and Talazoparib for the Treatment of Patients With Locally Advanced or Metastatic Colorectal or Gastroesophageal Cancer	NCT04511039	Advanced Malign... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Locally Advance... Locally Advance... Metastatic Colo... Metastatic Gast... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Stage III Color... Stage IIIA Colo... Stage IIIB Colo... Stage IIIC Colo... Stage IV Colore... Stage IVA Color... Stage IVB Color... Stage IVC Color...	Trifluridine an... Talazoparib Tos...	18 Years -	Roswell Park Cancer Institute

Spots Global Cancer Trial Database for pathologic stage iiia gastroesophageal junction adenocarcinoma