Decitabine With or Without Interferon Alfa-2b in Treating Patients With Unresectable or Metastatic Solid Tumors
Inhibition of DNA Methylation by 1-Hr Infusion of 5-aza-2'-Deoxycitidine (Decitabine) x 10 Days (M-F) With Escalating Doses of Sub-Q Pegylated (PEG) Interferon-alpha 2B (PEG-Intron): A Phase I Study With Molecular Correlates
調査の概要
詳細な説明
PRIMARY OBJECTIVES:
I. To assess toxicities of decitabine plus escalating doses of pegylated interferon alfa-2b (PEG-Intron) in patients with metastatic solid tumor.
II. To identify the dose-limiting toxicity of decitabine in combination with escalating doses of pegylated interferon alfa-2b in these patients.
III. To identify the maximum tolerated dose of pegylated interferon alfa-2b in combination with decitabine in these patients.
SECONDARY OBJECTIVES:
I. To evaluate pretreatment and post-treatment blood and tumor samples to identify changes in global (genomic) DNA methylation.
II. To evaluate pretreatment and post-treatment blood, skin and tumor samples to identify changes in Mage-1 mRNA and protein expression, DNMT-1 levels (due to sequestration by 5-azacytidine), p53 induction (evidence of DNA damage response), as well as changes in levels of 2'5'-oligoadenylate synthesis, MxA and HLA class I as indicators of interferon response.
III. To evaluate complete and partial response rates in patients receiving decitabine in combination with escalating doses of pegylated interferon alfa-2b.
OUTLINE:
This is a dose-escalation study of pegylated interferon alfa-2b. Patients are assigned to 1 of 2 treatment groups.
GROUP 1 (control): Patients receive decitabine IV over 1 hour on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression after the first course of treatment may crossover to receive treatment in group 2.
GROUP 2: Patients receive decitabine as in group 1 and pegylated interferon alfa-2b subcutaneously on days 1, 8, 15, and 22.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample, normal skin, and tissue biopsy collection at baseline and periodically during study. Blood, normal skin, and tissue samples are analyzed for global (genomic) DNA methylation (gene-promoter methylation, gene and protein expression, p53 induction by DNA damage) and interferon levels by high-performance (pressure) liquid chromatography and PCR methylation assays, and for pharmacodynamic studies.
After completion of study treatment, patients are followed at 28 days and then every 3 months.
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
-
-
Nevada
-
Las Vegas、Nevada、アメリカ、89135
- Nevada Cancer Institute-Summerlin Campus
-
-
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:
Biopsy-proven solid tumor
- Metastatic or unresectable disease
- Tumor amenable to biopsy
- No curative or more effective treatment for this disease exists, in the opinion of the investigator
- Measurable disease by scans as assessed by RECIST criteria
No untreated brain metastasis
- No longer receiving steroid therapy for previously treated brain metastasis
- Zubrod performance status of 0-2
- Bilirubin ≤ 1.5 times upper limit normal (ULN)
- SGOT or SGPT ≤ 2.5 times ULN (≤ 5 ULN if hepatic metastases present)
- Serum creatinine ≤ 1.5 times ULN
- Creatinine clearance ≥ 50 mL/min
- ANC > 1,500/μL
- Platelet count > 100,000/μL
- Hemoglobin > 9 g/dL (transfusion allowed)
- No NYHA class III-IV cardiac problems (e.g., congestive heart failure or myocardial infarction within the past 2 months)
- No severe and/or uncontrolled concurrent medical disease (e.g., uncontrolled diabetes, uncontrolled chronic renal or liver disease, or active uncontrolled infection [e.g., HIV])
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception during and for 3 months after completion of study therapy
- Willing to undergo biopsies
- No medical or psychological conditions that, in the opinion of the investigator, may preclude the patient's ability to tolerate or complete the treatment, or to grant reliable informed consent
- No other prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I, II, or III cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years
- No prior extensive pelvic irradiation or prolonged nucleoside analogue pretreatment
- At least 28 days since prior and no concurrent chemotherapy, radiotherapy, surgery, biological therapy, anticancer agent, or other investigational drug
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 |
|---|---|
|
アクティブコンパレータ：Group 1 (chemotherapy)
Patients receive decitabine IV over 1 hour on days 1-5 and 8-12.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients whose disease is not responding after the first course may crossover to group 2.
|
相関研究
与えられた IV
他の名前：
|
|
実験的：Group 2 (chemotherapy and antineoplastic agent)
Patients receive decitabine as in group 1 and pegylated interferon alfa-2b subcutaneously on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
相関研究
与えられた IV
他の名前：
Given SC
他の名前：
|
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 |
|---|---|---|
|
Toxicities as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
時間枠：Up to 28 days
|
The type, frequency, and severity of each toxicity will be reported.
|
Up to 28 days
|
|
Dose-limiting toxicity (DLT) of pegylated interferon alfa-2b when given with decitabine as assessed by NCI CTCAE version 3.0
時間枠：First 28-day course
|
DLT is defined as grade III drug-related non hematologic and/or grade IV drug-related hematologic toxicity.
|
First 28-day course
|
|
Maximum-tolerated dose (MTD) of pegylated interferon alfa-2b when given with decitabine as assessed by NCI CTCAE version 3.0
時間枠：First 28-day course
|
The MTD will be the dose level where not more than 1 case of a specific grade III-IV drug-related toxicity is observed, and either 2+toxicities have been observed at the next highest dose level, or the maximum dose-level of PEG-Intron has been reached.
|
First 28-day course
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Global (genomic) DNA methylation changes by high-performance liquid chromatography (HPLC)
時間枠：Baseline to up to day 1 of course 2
|
Repeated measures analysis of variance and other linear modeling techniques will be used.
|
Baseline to up to day 1 of course 2
|
|
Changes in expression of methylation-regulated genes in human biological tissues
時間枠：Baseline to up to day 1 of course 2
|
Repeated measures analysis of variance and other linear modeling techniques will be used.
|
Baseline to up to day 1 of course 2
|
|
Complete and partial response rates
時間枠：Up to 1 year
|
Up to 1 year
|
協力者と研究者
捜査官
- 主任研究者：Wolfram Samlowski、Nevada Cancer Institute-Summerlin Campus
研究記録日
主要日程の研究
研究開始
一次修了 (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-2009-00295 (レジストリ識別子：CTRP (Clinical Trial Reporting Program))
- CDR0000597624
- NVCI-0725
- NVCI 07-25 (その他の識別子：Nevada Cancer Institute-Summerlin Campus)
- 8224 (その他の識別子：CTEP)
- R21CA122270 (米国 NIH グラント/契約)
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。
実験用バイオマーカー分析の臨床試験
-
ORIOL BESTARD完了腎臓移植 | CMV感染スペイン, ベルギー
-
Central and North West London NHS Foundation TrustBritish HIV Association (BHIVA)まだ募集していませんHIV感染症 | B型肝炎
-
Hvidovre University HospitalElsassFonden終了しました
-
McGill University Health Centre/Research Institute...Northwestern University募集
-
Nantes University Hospital完了
-
Fundació Sant Joan de DéuStanley Medical Research Institute; Parc Sanitari Sant Joan de Déu; Hospital Sant Joan de Deu完了