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TMZ + Olaparib for MGMT Hypermethylated Colorectal Cancer | Clinical Trials | Clareo Health

COMPLETEDPHASE2

TMZ + Olaparib for MGMT Hypermethylated Colorectal Cancer

Temozolomide and Olaparib for O6-Methylguanine DNA Methyltransferase Promoter Hypermethylated Colorectal Cancer

NCT04166435•Yale University

Summary

This is a Phase II, non-randomized, open-label study to evaluate temozolomide in combination with olaparib in patients with MGMT promoter hypermethylated advanced colorectal cancer.

Detailed Description

This is a Phase II, non-randomized, open-label study to evaluate temozolomide in combination with olaparib in patients with MGMT promoter hypermethylated advanced colorectal cancer. Patients will receive temozolomide orally daily on days 1-7 and olaparib twice daily continuously. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatments patients are followed up at 30 days, and for patients that come off treatment for reasons other than disease progression, clinical assessments will continue every 6 weeks for the first year and every 12 weeks after the first year. PRIMARY OBJECTIVES: I. To determine the efficacy of TMZ in combination with olaparib in subjects with MGMT promoter hypermethylated advanced colorectal cancer by the overall response rate. SECONDARY OBJECTIVES: I. To determine the safety of TMZ in combination with olaparib. II. To estimate the progression free survival (PFS). III. To estimate overall survival (OS). EXPLORATORY OBJECTIVES: I. Characterize NGS profiling, patterns of DNA methylation, gene expression, and develop MGMT expression assays. II. Correlate molecular features with Gamma H2AX with response. III. Establish organoids for MGMT promoter hypermethylated colorectal cancer.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF).
•Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.
•For inclusion in i) the optional exploratory genetic research and ii) the optional biomarker research, patients must fulfill the following criteria:
•* Provision of informed consent for genetic research prior to collection of sample
•* Provision of informed consent for biomarker research prior to collection of sample \*\*If a patient declines to participate in the optional exploratory genetic research or the optional biomarker research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study.
•Individuals who are healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
•Individuals with histologically proven relapsed/refractory mismatch repair proficient / microsatellite stable metastatic colorectal adenocarcinoma.
•MGMT promoter hypermethylation on pre-screening.
•Patients must have had recurrence, progression or intolerance to standard therapy consisting of at least 2 prior standard regimens (containing a fluoropyrimidine plus a platinum analogue and/or irinotecan) for metastatic disease. In the case where all chemotherapy agents are used concurrently (I.e. FOLFOXIRI +/- Bevacizumab) 1 prior treatment regimen is acceptable after discussion with the principal investigator. Relapse within 6 months of completing adjuvant chemotherapy is considered one line of therapy in the metastatic setting.
•Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
+26 more criteria

Exclusion Criteria

•Other malignancy unless curatively treated with no evidence of disease for ≥5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma.
•Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation \>500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome.
•Persistent toxicities (Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia.
•Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML.
•Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
•Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
•Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
•Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
•Patients with known active hepatitis (i.e. Hepatitis B or C).
•Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible.
+8 more criteria

Locations (1)

Yale New Haven Hospital

New Haven, Connecticut, United States

Key Dates

Start Date

June 17, 2020

Primary Completion Date

January 6, 2022

Completion Date

June 12, 2023

Last Updated

September 6, 2023

Enrollment

ACTUAL participants

Conditions

Colorectal Cancer

Interventions

Temozolomide + Olaparib

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: September 6, 2023Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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TMZ + Olaparib for MGMT Hypermethylated Colorectal Cancer

Inclusion Criteria

Exclusion Criteria

Clinical Trial of an Anti-cancer Drug, CA-4948 (Emavusertib), in Combination With Chemotherapy Treatment (FOLFOX Plus Bevacizumab) in Metastatic Colorectal Cancer

Testing the Combination of Two Anti-cancer Drugs, DS-8201a and AZD6738, for The Treatment of Advanced Solid Tumors Expressing the HER2 Protein or Gene, The DASH Trial

Study of Dato-DXd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03)

A Study of ART0380 for the Treatment of Advanced or Metastatic Solid Tumors

Open-Label Study of BBO-10203 in Subjects With Advanced Solid Tumors

Evaluation of the Safety and Efficacy of Treatment w/High Dose Melphalan Given Directly Into the Liver Followed by Treatment w/Approved Cancer Treatment or Approved Cancer Treatment Alone in Patients w/ Metastatic Colorectal Cancer w/Liver Dominant Disease