Azacitidine and Entinostat in Treating Patients With Metastatic Colorectal Cancer

• Status: Completed
• Trial end date: 2014-05-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Azacitidine; Entinostat; Histone Deacetylase Inhibitors

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

• ANC ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

• AST and ALT ≤ 2.5 times ULN

• Creatinine normal OR creatinine clearance ≥ 60 mL/min

• Negative pregnancy test

• Not pregnant or nursing

• Fertile patients must use effective contraception

• Sensory neuropathy ≤ grade 2 allowed

• Willing to provide tissue and blood samples

• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to entinostat, azacitidine, mannitol, or other agents used in the study

• No uncontrolled intercurrent illness including, but not limited to, any of the following:

• Ongoing or active infection

• NYHA class II-IV symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia

• Psychiatric illness and/or social situations that would limit compliance with study requirements

• No history of severe bleeding without thrombocytopenia

• No concurrent radiotherapy including palliative treatment

• Toxicities from prior therapy have resolved to ≤ grade 1

• More than 4 weeks since prior chemotherapy (> 6 weeks for nitrosoureas or mitomycin C)

• More than 4 weeks since prior major surgical procedure

• No prior histone deacetylase inhibitors (including valproic acid) or demethylating agents

• No concurrent investigational agents

• No concurrent combination antiretroviral therapy in HIV-positive patients

• No concurrent investigational or commercial anticancer agents or therapies