Actively Recruiting

Phase 1
Phase 2
Age: 18Years +
All Genders
NCT05691491

Testing the Combination of the Anti-Cancer Drugs Temozolomide and M1774 to Evaluate Their Safety and Effectiveness

Led by National Cancer Institute (NCI) · Updated on 2026-05-13

58

Participants Needed

23

Research Sites

178 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

This phase I/II trial studies the side effects and best dose of temozolomide and M1774 and how well they works in treating patients with cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and may have spread to nearby tissue, lymph nodes, or distant parts of the body (advanced). Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill tumor cells and slow down or stop tumor growth. M1774 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Adding M1774 to temozolomide may shrink or stabilize cancer for longer than temozolomide alone.

CONDITIONS

Official Title

Testing the Combination of the Anti-Cancer Drugs Temozolomide and M1774 to Evaluate Their Safety and Effectiveness

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Patients must have a confirmed diagnosis of metastatic advanced cancer.
  • In dose escalation, patients with solid tumors positive for MGMT promoter hypermethylation or extracranial solid tumors where temozolomide is standard care.
  • Phase 2 includes only mismatch repair proficient/microsatellite stable colorectal cancer patients with MGMT promoter hypermethylation.
  • Patients must have progressed after available therapies or be intolerant/refuse standard treatment; no prior temozolomide or ATR inhibitor use.
  • For phase 2 colorectal cancer patients, prior treatment with 5-fluorouracil, irinotecan, and oxaliplatin is required.
  • Age 18 years or older.
  • Measurable disease on CT or MRI per RECIST v1.1.
  • ECOG performance status 0 to 2 or Karnofsky 60% or higher.
  • Adequate blood counts and organ function.
  • HIV patients on effective therapy with undetectable viral load eligible.
  • Controlled hepatitis B or treated hepatitis C infection.
  • Patients with treated brain metastases stable for 4 weeks.
  • Patients with prior or concurrent malignancies not interfering with study.
  • Cardiac function class 2B or better.
  • Women and men must agree to use contraception during and after treatment.
  • Ability to understand and sign informed consent.
Not Eligible

You will not qualify if you...

  • Patients not recovered from prior cancer therapy side effects greater than grade 1, except alopecia and neuropathy up to grade 2.
  • History of allergic reaction to temozolomide, M1774, or similar compounds.
  • Uncontrolled illnesses.
  • Pregnant or breastfeeding women.
  • History of ataxia telangiectasia.
  • Unable to swallow oral medication or with gastrointestinal disorders affecting absorption.
  • Cannot discontinue proton-pump inhibitors; restrictions on other acid-reducing medications.
  • Extensive radiation involving more than 30% of bone marrow.
  • QTcF interval greater than 480 ms on ECG.

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 23 locations

1

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California, United States, 92612

Actively Recruiting

2

UC San Diego Moores Cancer Center

La Jolla, California, United States, 92093

Active, Not Recruiting

3

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, United States, 92868

Actively Recruiting

4

Yale University

New Haven, Connecticut, United States, 06520

Actively Recruiting

5

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut, United States, 06611

Actively Recruiting

6

Memorial Hospital East

Shiloh, Illinois, United States, 62269

Actively Recruiting

7

University of Kansas Clinical Research Center

Fairway, Kansas, United States, 66205

Actively Recruiting

8

University of Kansas Cancer Center

Kansas City, Kansas, United States, 66160

Actively Recruiting

9

University of Kansas Cancer Center-Overland Park

Overland Park, Kansas, United States, 66210

Actively Recruiting

10

University of Kansas Hospital-Indian Creek Campus

Overland Park, Kansas, United States, 66211

Actively Recruiting

11

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, United States, 66205

Actively Recruiting

12

National Cancer Institute Developmental Therapeutics Clinic

Bethesda, Maryland, United States, 20892

Actively Recruiting

13

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, United States, 63376

Actively Recruiting

14

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, United States, 63141

Actively Recruiting

15

University of Kansas Cancer Center - North

Kansas City, Missouri, United States, 64154

Actively Recruiting

16

University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri, United States, 64064

Actively Recruiting

17

University of Kansas Cancer Center at North Kansas City Hospital

North Kansas City, Missouri, United States, 64116

Suspended

18

Washington University School of Medicine

St Louis, Missouri, United States, 63110

Actively Recruiting

19

Siteman Cancer Center-South County

St Louis, Missouri, United States, 63129

Actively Recruiting

20

Siteman Cancer Center at Christian Hospital

St Louis, Missouri, United States, 63136

Actively Recruiting

21

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States, 73104

Actively Recruiting

22

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, United States, 15232

Actively Recruiting

23

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States, 37232

Actively Recruiting

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How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SEQUENTIAL

Primary Purpose

TREATMENT

Number of Arms

1

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