Azacitidine and Entinostat in Treating Patients With Metastatic Colorectal Cancer
Phase II Study of Azacitadine and Entinostat in Patients With Metastatic Colorectal Cancer
연구 개요
상세 설명
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.
연구 유형
등록 (실제)
단계
- 2 단계
연락처 및 위치
연구 장소
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Arizona
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Scottsdale, Arizona, 미국, 85259
- Mayo Clinic in Arizona
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California
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Los Angeles, California, 미국, 90033
- University of Southern California/Norris Cancer Center
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Florida
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Jacksonville, Florida, 미국, 32224-9980
- Mayo Clinic in Florida
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Maryland
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Baltimore, Maryland, 미국, 21287
- Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
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Michigan
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Detroit, Michigan, 미국, 48201
- Wayne State University/Karmanos Cancer Institute
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Minnesota
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Maplewood, Minnesota, 미국, 55109
- Minnesota Oncology Hematology PA-Maplewood
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Rochester, Minnesota, 미국, 55905
- Mayo Clinic
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Saint Louis Park, Minnesota, 미국, 55416
- Metro-Minnesota CCOP
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Saint Paul, Minnesota, 미국, 55102
- United Hospital
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Stillwater, Minnesota, 미국, 55082
- Lakeview Hospital
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Missouri
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Saint Louis, Missouri, 미국, 63110
- Washington University School of Medicine
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Pennsylvania
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Pittsburgh, Pennsylvania, 미국, 15232
- University of Pittsburgh
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Pittsburgh, Pennsylvania, 미국, 15232
- University of Pittsburgh Cancer Institute
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Wisconsin
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Madison, Wisconsin, 미국, 53792
- University of Wisconsin Hospital and Clinics
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: 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.
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상관 연구
구두로 주어진
다른 이름들:
주어진 SC
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Confirmed Tumor Response
기간: At 6 month evaluation
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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.
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At 6 month evaluation
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Time to Progression
기간: From the start of treatment to the earliest of the date documenting disease progression, assessed up to 3 years
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Time to disease progression (TTP) is defined as the time from the start of treatment to the earliest of the date documenting disease progression or most recent assessment for patients having no progression.
The distribution of TTP is estimated using the method of Kaplan-Meier.
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From the start of treatment to the earliest of the date documenting disease progression, assessed up to 3 years
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공동 작업자 및 조사자
수사관
- 수석 연구원: Nilofer Azad, Mayo Clinic
간행물 및 유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- NCI-2010-02024 (레지스트리 식별자: CTRP (Clinical Trial Reporting Program))
- P30CA015083 (미국 NIH 보조금/계약)
- N01CM00099 (미국 NIH 보조금/계약)
- N01CM00038 (미국 NIH 보조금/계약)
- 8341 (기타 식별자: CTEP)
- CDR0000670136
- MC084B (기타 식별자: Mayo Clinic)
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