Testing the Combination of the Anti-Cancer Drugs Temozolomide and M1774 to Evaluate Their Safety and Effectiveness
Start Date
9/28/2023
Completion Date
3/1/2027
Summary
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.
Detailed Description
PRIMARY OBJECTIVE: I. To determine the maximum tolerated dose of the combination of temozolomide (TMZ) and tuvusertib (M1774). SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To determine the overall response rate. III. To estimate progression free survival. IV. To estimate overall survival. V. To determine the recommended phase 2 dose of the combination of TMZ and M1774. EXPLORATORY OBJECTIVES: I. Correlate MGMT promoter hypermethylation, MGMT expression and tumor-infiltrating lymphocytes (TILs) with efficacy endpoints of response rate, progression free survival, and overall survival. II. Assess pre and post treatment tumor biopsies for changes in tumor mutational burden, tumor associated neo-antigens and microsatellite status by whole exome sequencing. III. Measure changes in peripheral blood mononuclear cell populations with treatment. IV. Assess liquid biopsies by circulating tumor (ct)DNA for changes in tumor mutational burden and microsatellite status by whole exome sequencing. OUTLINE: This is a phase I, dose-escalation study of temozolomide and tuvusertib followed by a phase II study. Patients receive tuvusertib orally (PO) once daily (QD) on days 1-7 and temozolomide PO QD on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan and magnetic resonance imaging (MRI) as well as collection of blood samples throughout the trial. Patients also undergo a biopsy at baseline and may undergo one on study and/or time of progression. After completion of study treatment, patients are followed up at 4 weeks (if clinically indicated), and then every 3 months for up to 2 years.
Eligibility Criteria
Age Range: 18 years to No maximum
Interventions
Biopsy Procedure
Biospecimen Collection
Computed Tomography
Magnetic Resonance Imaging
Temozolomide
Tuvusertib
Conditions
Locations
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California 92612
United States
UC San Diego Moores Cancer Center
La Jolla, California 92093
United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California 92868
United States
Yale University
New Haven, Connecticut 06520
United States
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut 06611
United States
Memorial Hospital East
Shiloh, Illinois 62269
United States
University of Kansas Clinical Research Center
Fairway, Kansas 66205
United States
University of Kansas Cancer Center
Kansas City, Kansas 66160
United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas 66210
United States
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas 66211
United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas 66205
United States
National Cancer Institute Developmental Therapeutics Clinic
Bethesda, Maryland 20892
United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri 63376
United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri 63141
United States
University of Kansas Cancer Center - North
Kansas City, Missouri 64154
United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri 64064
United States
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri 64116
United States
Washington University School of Medicine
St Louis, Missouri 63110
United States
Siteman Cancer Center-South County
St Louis, Missouri 63129
United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri 63136
United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania 15232
United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee 37232
United States