Phase II Study of Azacitadine and Entinostat in Patients With Metastatic Colorectal Cancer
Overview
- Phase
- Phase 2
- Intervention
- entinostat
- Conditions
- Recurrent Colon Cancer
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 47
- Locations
- 14
- Primary Endpoint
- Confirmed Tumor Response
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
This phase II trial is studying how well giving azacitidine together with entinostat works in treating patients with metastatic colorectal cancer. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Entinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving azacitidine together with entinostat may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the preliminary efficacy via Response Evaluation Criteria In Solid Tumors (RECIST) response rate of the combination of azacitidine and entinostat in patients with metastatic colorectal cancer. SECONDARY OBJECTIVES: I. Explore the effects of azacitidine and entinostat on time to progression in patients with metastatic colorectal cancer. II. To assess the toxicity for combination azacitidine and entinostat therapy. TERTIARY OBJECTIVES: I. Evaluate changes in promoter methylation of selected genes from DNA in circulating serum samples. II. To determine changes in histone deacetylase activity and acetylation of H3 and H4 histones in pre- and post-treatment tumor biopsies. III. To evaluate correlations between these molecular effects and clinical outcomes (response, time to progression). IV. To correlate response rates by RECIST criteria versus response rates determined be EASL (change in tumor enhancement). OUTLINE: This is a multicenter study. Patients receive azacitidine subcutaneously on days 1-5 and 8-10 and oral entinostat on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Blood and tumor tissue samples are collected at baseline and periodically during courses 1-3 for DNA methylation, histone deacetylation activity, and acetylation of H3 and H4 histones analysis by PCR, western blot, and RT-PCR assays. Pharmacogenomic studies may also be conducted. After completion of study therapy, patients are followed up every 3-6 months for up to 3 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed metastatic colorectal cancer
- •Measurable disease
- •Patient has failed ≥ 2 prior chemotherapy regimens
- •Not a candidate for curative resection
- •No CNS metastases within ≤ 2 years
- •Treatment for brain metastasis and whole brain disease that has remained stable for \> 3 months allowed
- •Patients who have not been treated with steroid therapy may be allowed
- •ECOG performance status 0-1
- •Life expectancy ≥ 12 weeks
- •Leukocytes ≥ 3,000/mm\^3
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (entinostat, azacitidine)
Patients receive azacitidine subcutaneously on days 1-5 and 8-10 and oral entinostat on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: entinostat
Treatment (entinostat, azacitidine)
Patients receive azacitidine subcutaneously on days 1-5 and 8-10 and oral entinostat on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: azacitidine
Treatment (entinostat, azacitidine)
Patients receive azacitidine subcutaneously on days 1-5 and 8-10 and oral entinostat on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
Confirmed Tumor Response
Time Frame: At 6 month evaluation
Each evaluable patient is classified as having a confirmed tumor response if they have either a complete response (CR) or partial response (PR) lasts at least 4 weeks. Tumor response is measured by using RECIST v1.1 (Response Evaluation Criteria in Solid Tumors). A CR is defined as a disappearance of all target lesions, and each target lymph node must have reduction in short axis to \<1.0 cm. A PR is defined as a 30% decrease in the sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation, compared to pre-treatment measurements. The confirmed response rate is calculated as the number of confirmed CR+PR, divided by the total number of evaluable patients, with 95% confidence intervals estimated using the approach of Duffy and Santner.
Secondary Outcomes
- Time to Progression(From the start of treatment to the earliest of the date documenting disease progression, assessed up to 3 years)