A Phase 1/2 Trial Evaluating the Combination of Temozolomide and the Ataxia Telangiectasia and Rad3-Related Inhibitor M1774
National Cancer Institute (NCI)
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.
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,…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Patients must have histologically or cytologically confirmed diagnosis of metastatic advanced cancer. * In dose escalation, any solid tumor patients with either O6-methylguanine DNA methyltransferase (MGMT) promoter hypermethylation positivity on testing / pre-screening of archival tissue OR an extracranial solid tumor where TMZ is considered a standard of care per National Comprehensive Cancer Network (NCCN) guidelines (neuroendocrine tumor, small cell lung cancer, melanoma or soft tissue sarcoma). The tumor lesion must be safely accessible to a mandatory biopsy. Patien…
Interventions
- ProcedureBiopsy Procedure
Undergo biopsy
- ProcedureBiospecimen Collection
Undergo collection of blood samples
- ProcedureComputed Tomography
Undergo CT scan
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- DrugTemozolomide
Given orally (PO)
- DrugTuvusertib
Given PO
Locations (23)
- UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory CareIrvine, California
- UC San Diego Moores Cancer CenterLa Jolla, California
- UC Irvine Health/Chao Family Comprehensive Cancer CenterOrange, California
- Yale UniversityNew Haven, Connecticut
- Smilow Cancer Hospital Care Center-TrumbullTrumbull, Connecticut
- Memorial Hospital EastShiloh, Illinois