Azacitidine and Entinostat in Treating Patients With Stage I Non-Small Cell Lung Cancer That Has Been Removed By Surgery
Randomized Phase II Trial of Adjuvant Combined Epigenetic Therapy With 5-Azacitidine and Entinostat in Resected Stage I Non-small Cell Lung Cancer Versus Standard Care
調査の概要
詳細な説明
PRIMARY OBJECTIVES:
I. To assess the effect of 5-azacitidine and entinostat on the hazard of 3 year progression-free survival in patients with resected stage I non-small cell lung cancer.
SECONDARY OBJECTIVES:
I. To assess the safety, tolerability and toxicity of entinostat and 5-azacitidine in patients with resected stage I non-small cell lung cancer.
II. To explore the effect of entinostat and 5-azacitidine on median disease-free and overall survival in patients with resected stage I non-small cell lung cancer.
III. To assess the pharmacodynamic effects of 5-azacitidine and entinostat on DNA methylation and gene re-expression in patients with resected stage I NSCLC through analysis of sputum.
IV. To estimate the effect of entinostat and 5-azacitidine on progression free survival comparing patients with N2 lymph nodes categorized as methylated pre-treatment with those who are categorized as unmethylated.
V. To establish factors that predict clinical outcome in patients treated with combination epigenetic therapy by performing genome-wide analyses on pre-treatment tumor DNA.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive azacitidine subcutaneously (SC) on days 1-5 and 8-10 and entinostat orally (PO) once daily (QD) on days 3 and 10. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive standard of care.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 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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California
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Los Angeles、California、アメリカ、90033
- USC / Norris Comprehensive Cancer Center
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Florida
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Tampa、Florida、アメリカ、33612
- Moffitt Cancer Center
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Maryland
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Annapolis、Maryland、アメリカ、21401
- Anne Arundel Medical Center
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Baltimore、Maryland、アメリカ、21204
- Greater Baltimore Medical Center
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Baltimore、Maryland、アメリカ、21224
- Johns Hopkins Bayview Medical Center
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Baltimore、Maryland、アメリカ、21231
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
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Pennsylvania
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Pittsburgh、Pennsylvania、アメリカ、15232
- University of Pittsburgh Cancer Institute
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Tennessee
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Nashville、Tennessee、アメリカ、37232
- Vanderbilt-Ingram Cancer Center
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Texas
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Dallas、Texas、アメリカ、75390
- University of Texas Southwestern Medical Center
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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:
- Patients must be status post complete (R0) surgical resection of pathologically-proven NSCLC (stage IA-IB according to AJCC version 7)
- Patients must be at least 4 weeks out from completion of surgery
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Absolute neutrophil count >= 1,000/mcL
- Platelets >= 100,000/mcL
- Total bilirubin =< 1.5 X institutional upper limit of normal
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
- Creatinine =< 1.5 X institutional upper limit of normal
- The effects of entinostat and 5-azacitidine on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Patients must be within 8 weeks of completing surgery
- Patients who have received prior chemotherapy or radiation for treatment of their current diagnosis of lung cancer
- Patients with sub-lobar resections (ie: wedge resection or segmentectomy)
- Patients without mediastinal lymph node specimens from mediastinoscopy or surgery (at least level R4 or 7 for right sided tumors OR at least level 5, 6 or 7 for left sided tumors)
- Patients may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to entinostat, 5-azacitidine or other agents used in the study
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study because entinostat and 5-azacitidine are agents with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with entinostat or 5-azacitidine, breastfeeding should be discontinued if the mother is treated on this protocol; these potential risks may also apply to other agents used in this study
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with entinostat or 5-azacitidine; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy
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:ランダム化
- 介入モデル:並列代入
- 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:Arm I (azacitidine, entinostat)
Patients receive azacitidine SC on days 1-5 and 8-10 and entinostat PO QD on days 3 and 10.
Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
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相関研究
与えられたPO
他の名前:
与えられた SC
他の名前:
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介入なし:Arm II (standard of care)
Patients receive standard of care.
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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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Disease-free Survival (DFS)
時間枠:3 years
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The DFS hazard rate and 95% confidence interval will be reported.
At this time, event time distributions for disease-free survival in the two arms will be estimated with the method of Kaplan and Meier and compared using a stratified Cox-proportional hazards model (stratified for stage IA vs IB) with a two-sided alpha of 10%.
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3 years
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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 |
---|---|---|
Factors That Predict Clinical Outcome in Patients Treated With Combination Epigenetic Therapy in Terms of Epigenomic Data Generated From the Illumina Platform
時間枠:Up to 2 years
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The study was terminated early due to poor accrual since the requirement of clinic administration of the 5AZA daily and post-operative patients not wanting 6 months of treatment.
For this reason, 13 pts were enrolled and data was not analyzed, for which we are unable to make any conclusions or report results.
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Up to 2 years
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Median Disease-free Survival
時間枠:Up to 5 years
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Determined by the method determined by Kaplan and Meier.
Estimated with 95% confidence intervals.
Cox proportional hazard modeling will be used for multivariate analysis.
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Up to 5 years
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Number of Relapses and Deaths Per Total Time of Follow-up Comparing Patients With N2 Lymph Nodes in Terms of Methylated and Unmethylated
時間枠:Up to 5 years
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Kaplan Meier curves will be used.
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Up to 5 years
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Overall Survival
時間枠:Up to 5 years
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Determined by the method determined by Kaplan and Meier.
Estimated with 95% confidence intervals.
Cox proportional hazard modeling will be used for multivariate analysis.
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Up to 5 years
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Presence of Methylation Patterns
時間枠:Up to 2 years
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McNemar's test will be used to compare the change in methylation after treatment in sputum.
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Up to 2 years
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Toxicities Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
時間枠:Up to 5 years
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Simple descriptive statistics will be utilized to display the data.
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Up to 5 years
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協力者と研究者
捜査官
- 主任研究者:Charles Rudin、Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
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 (実際)
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-2012-02901 (レジストリ識別子:CTRP (Clinical Trial Reporting Program))
- P30CA006973 (米国 NIH グラント/契約)
- NA_00038631
- J1037 (その他の識別子:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital)
- 8311 (その他の識別子:CTEP)
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
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