Trials / Active Not Recruiting

Active Not RecruitingNCT03641313

Berzosertib and Irinotecan in Treating Patients With Progressive, Metastatic, or Unresectable TP53 Mutant Gastric or Gastroesophageal Junction Cancer

A Phase 2 Single-Arm Study of M6620 in Combination With Irinotecan in Patients With Progressive TP53 Mutant Gastric and Gastro-Esophageal Junction Cancer

Status: Active Not Recruiting
Phase: Phase 2
Study type: Interventional
Enrollment: 17 (actual)

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

Summary

This phase II trial studies the how well berzosertib and irinotecan work in treating patients with gastric or gastroesophageal junction cancer that is growing, spreading or getting worse (progressive), has spread to other places in the body (metastatic), or cannot be removed by surgery (unresectable). Berzosertib may stop the growth of tumor cells by blocking some of the enzymes needed for growth. Chemotherapy drugs, such as irinotecan, 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 berzosertib and irinotecan may work better than irinotecan alone in treating patients with gastric and gastroesophageal junction cancer.

Detailed description

PRIMARY OBJECTIVE: I. Determine objective response rate (ORR) superiority (target 25%) in TP53 mutant patients with progressive metastatic or unresectable gastric/gastroesophageal junction (GEJ) cancer who receive berzosertib (M6620) and irinotecan compared to ORR (5%) in historical control patients treated with single agent irinotecan alone. SECONDARY OBJECTIVES: I. Determine duration of response (DOR), time to progression (TTP), progression-free survival (PFS), and overall survival (OS) superiority in TP53 mutant gastric/GEJ cancer patients who receive M6620 and irinotecan compared to these measures in historical control patients treated with irinotecan alone. II. Perform the following correlative studies in 9 patients: gamma-H2AX, KAP1 phosphorylated (p)-Ser 824 and p-ATR analysis from biopsies collected at 24 hours (+/- 1 hour) post-irinotecan infusion on cycle 1 day 2 (C1D2) and at 24 hours (+/- 1 hour) post-M6620 on cycle 2 day 2 (C2D2). EXPLORATORY OBJECTIVES: I. Determine ORR, DOR, TTP, PFS, and OS in patients with other concomitant damage response defects (DDRD), such as mutations in BRCA1, BRCA2, MRE11, RAD50, RAD51, RAD52, RAD54L, NBN, ATM, H2AX, PALB2, RPA, BRIP1, BARD1, ATR, ATRX, CHK1, CHK2, MDM2, MDM4, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL, treated with the experimental combination. II. Determine whether patients with first line platinum sensitivity (PFS \> 3 months) demonstrate improved ORR, DOR, TTP, PFS, and OS compared to patients who were platinum insensitive (PFS \< 3 months). OUTLINE: Patients receive irinotecan intravenously (IV) over 90 minutes and berzosertib IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo endoscopic or computed tomography (CT) assisted biopsy and magnetic resonance imaging (MRI) on study. After completion of study treatment, patients are followed up for 30 days and then every 2 months for up to 1 year.

Conditions

Interventions

Type	Name	Description
DRUG	Berzosertib	Given IV
PROCEDURE	Computed Tomography Assisted Biopsy	Undergo CT assisted biopsy
PROCEDURE	Endoscopic Biopsy	Undergo endoscopic biopsy
DRUG	Irinotecan	Given IV
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI

Timeline

Start date: 2020-11-16
Primary completion: 2024-07-01
Completion: 2027-01-28
First posted: 2018-08-22
Last updated: 2026-04-13
Results posted: 2025-07-08

Locations

31 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT03641313. Inclusion in this directory is not an endorsement.