Trials / Active Not Recruiting

Active Not RecruitingNCT04535401

Testing the Addition of an Anticancer Drug, BAY 1895344, to the Usual Chemotherapy With FOLFIRI in Advanced or Metastatic Cancers of the Stomach and Intestines

Phase I/Ib Trial of ATR Inhibitor BAY 1895344 in Combination With FOLFIRI in GI Malignancies With a Focus on Metastatic Colorectal and Gastric/Gastroesophageal Cancers

Status: Active Not Recruiting
Phase: Phase 1
Study type: Interventional
Enrollment: 10 (actual)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase I trial investigates the best dose, possible benefits and/or side effects of BAY 1895344 in combination with FOLFIRI in treating patients with stomach or intestinal cancer that that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or has spread from where it first started (primary site) to other places in the body (metastatic). BAY 1895344 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as irinotecan, fluorouracil, and leucovorin, (called FOLFIRI in short) 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. Giving BAY 1895344 in combination with FOLFIRI may help shrink advanced or metastatic stomach and/or intestinal cancer.

Detailed description

PRIMARY OBJECTIVE: I. Determine the safety and maximum tolerated dose (MTD) of elimusertib (BAY 1895344) with leucovorin calcium, fluorouracil, and irinotecan hydrochloride (FOLFIRI). SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity by overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). II. Determine the response and clinical benefit rate (complete response + partial response + stable disease) of BAY 1895344 with FOLFIRI in colorectal and gastric/gastroesophageal cancers. III. Evaluate tumor and peripheral blood mononuclear cell (PBMC) deoxyribonucleic acid (DNA) damage signaling in the context of the chemotherapy backbone alone and when combined with BAY 1895344. IV. Evaluate the pharmacokinetics (PK) profile of fluorouracil (5-FU) and irinotecan. V. Evaluate the PK profile of BAY 1895344. VI. Evaluate the relationship between ATM status by immunohistochemistry (IHC) and clinical efficacy of the BAY 1895344/FOLFIRI combination. EXPLORATORY OBJECTIVES: I. Evaluate the exposure-response relationship between drug exposures and toxicity and response, and UGT1A1 genotype. II. Evaluate the relationship between tumor mutations and clinical efficacy of the BAY 1895344/FOLFIRI combination. OUTLINE: This is a dose-escalation study of elimusertib, irinotecan, and fluorouracil with fixed-dose leucovorin followed by a dose-expansion study. Patients receive elimusertib orally (PO) once daily (QD) on days 2, 3, 16, and 17 and irinotecan hydrochloride intravenously (IV) over 90 minutes, fluorouracil IV over 46 hours, and leucovorin calcium IV on days 1 and 15. Cycles repeat every 28 day in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy during screening and on study and blood sample collection and imaging throughout the study. After completion of study treatment, patients are followed up for 30 days and then every 3 months for up to 1 year or until their disease gets worse or they begin a new treatment for their cancer.

Conditions

Interventions

Type	Name	Description
PROCEDURE	Biopsy	Undergo tumor biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Diagnostic Imaging	Undergo imaging
DRUG	Elimusertib	Given PO
DRUG	Fluorouracil	Given IV
DRUG	Irinotecan Hydrochloride	Given IV
DRUG	Leucovorin Calcium	Given IV

Timeline

Start date: 2021-08-13
Primary completion: 2024-03-29
Completion: 2025-04-29
First posted: 2020-09-02
Last updated: 2024-10-10

Locations

10 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT04535401. Inclusion in this directory is not an endorsement.