Azacitidine and Entinostat in Treating Patients With Metastatic Colorectal Cancer
Phase II Study of Azacitadine and Entinostat in Patients With Metastatic Colorectal Cancer
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
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Arizona
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Scottsdale、Arizona、アメリカ、85259
- Mayo Clinic in Arizona
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California
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Los Angeles、California、アメリカ、90033
- University of Southern California/Norris Cancer Center
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Florida
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Jacksonville、Florida、アメリカ、32224-9980
- Mayo Clinic in Florida
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Maryland
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Baltimore、Maryland、アメリカ、21287
- Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
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Michigan
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Detroit、Michigan、アメリカ、48201
- Wayne State University/Karmanos Cancer Institute
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Minnesota
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Maplewood、Minnesota、アメリカ、55109
- Minnesota Oncology Hematology PA-Maplewood
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Rochester、Minnesota、アメリカ、55905
- Mayo Clinic
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Saint Louis Park、Minnesota、アメリカ、55416
- Metro-Minnesota CCOP
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Saint Paul、Minnesota、アメリカ、55102
- United Hospital
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Stillwater、Minnesota、アメリカ、55082
- Lakeview Hospital
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Missouri
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Saint Louis、Missouri、アメリカ、63110
- Washington University School of Medicine
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Pennsylvania
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Pittsburgh、Pennsylvania、アメリカ、15232
- University of Pittsburgh
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Pittsburgh、Pennsylvania、アメリカ、15232
- University of Pittsburgh Cancer Institute
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Wisconsin
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Madison、Wisconsin、アメリカ、53792
- University of Wisconsin Hospital and Clinics
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：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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相関研究
経口投与
他の名前：
与えられた SC
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Confirmed Tumor Response
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Time to Progression
時間枠：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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協力者と研究者
捜査官
- 主任研究者：Nilofer Azad、Mayo Clinic
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- NCI-2010-02024 (レジストリ識別子：CTRP (Clinical Trial Reporting Program))
- P30CA015083 (米国 NIH グラント/契約)
- N01CM00099 (米国 NIH グラント/契約)
- N01CM00038 (米国 NIH グラント/契約)
- 8341 (その他の識別子：CTEP)
- CDR0000670136
- MC084B (その他の識別子：Mayo Clinic)
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