Bevacizumab and Cetuximab With or Without Irinotecan in Treating Patients With Irinotecan-Refractory Metastatic Colorectal Cancer
A Randomized Phase II Study of Bevacizumab in Combination With Cetuximab Plus Irinotecan, or in Combination With Cetuximab Alone, in Irinotecan-Refractory Colorectal Cancer
調査の概要
状態
詳細な説明
PRIMARY OBJECTIVES:
I. Evaluate time to tumor progression in patients with irinotecan-refractory metastatic colorectal cancer treated with bevacizumab and cetuximab with or without irinotecan.
II. Evaluate objective response rate in patients treated with these regimens. III. Evaluate overall survival of patients treated with these regimens. IV. Evaluate safety, tolerability, and adverse event profiles of these regimens in these patients.
V. Correlate a panel of molecular markers (e.g., those involved in the epidermal growth factor receptor signaling pathway, angiogenic pathway, and irinotecan metabolism) with clinical outcome in patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, ECOG performance status (0 vs 1), and albumin (> 3.0 g/dL vs ≤ 3.0 g/dL). Patients are randomized to 1 of 2 treatment arms.
ARM A: Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36; bevacizumab IV over 30-90 minutes on days 1*, 15, and 29 OR on days 1 and 22; and irinotecan IV over 30-90 minutes (at the same dose and schedule that the patient previously received) beginning on day 1.
ARM B: Patients receive cetuximab as in Arm A and bevacizumab IV over 30-90 minutes on days 1*, 15, and 29.
NOTE: *Bevacizumab is given on day 2 (instead of day 1) of course 1, and is given on day 1 of subsequent courses.
In both arms, courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Patients are followed 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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New York
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New York、New York、アメリカ、10065
- Memorial Sloan-Kettering Cancer 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:
Histologically or cytologically confirmed colorectal cancer
- Metastatic disease by diagnostic imaging studies
Measurable disease
- At least 1 unidimensionally measurable lesion with minimum lesion size at least twice the slice thickness of the imaging study used
Refractory to irinotecan, evidenced by clinical documentation
- Received at least 1 prior irinotecan-containing chemotherapy regimen for metastatic disease and progressed during or within 6 weeks after completion of therapy
Must have received prior irinotecan according to 1 of the following schedules:
- Weekly administration with a starting dose of 100-125 mg/m^2
- Biweekly administration (every other week) with a starting dose of approximately 180 mg/m^2
- Once every three weekly administration with a starting dose of 300-350 mg/m^2
- No known brain metastases
- No prior primary CNS tumors
- Performance status - ECOG 0-1
- Performance status - Karnofsky 80-100%
- More than 3 months
- WBC >= 3,000/mm^3
- Absolute neutrophil count >= 1,500/mm^3
- Platelet count >= 100,000/mm^3
- Hemoglobin >= 9 g/dL
- No bleeding diathesis or coagulopathy
- Bilirubin normal
- AST and ALT =< 2.5 times upper limit of normal (ULN) (5 times ULN in the presence of known liver metastases)
- INR < 1.5 (for patients receiving warfarin)
- Creatinine =< ULN
- Creatinine clearance ≥ 60 mL/min
- No proteinuria
- No prior stroke
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No uncontrolled hypertension
- No clinically significant cardiac arrhythmia
None of the following arterial thromboembolic events within the past 6 months:
- Myocardial infarction
- Cerebrovascular accident
- Transient ischemic attack
- Unstable angina
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 3 months after study participation
- No significant traumatic injury within the past 28 days
- No grade 3 or greater neurotoxicity
- No uncontrolled seizures
- No prior allergic reactions attributed to compounds of similar chemical or biological composition to study agents
- No prior irinotecan intolerance
- No ongoing or active infection requiring parenteral antibiotics
- No serious nonhealing active wound, ulcer, or bone fracture
- No psychiatric illness or social situation that would preclude study compliance
- No other concurrent uncontrolled illness that would preclude study participation
- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
- No prior cetuximab
- No other prior epidermal growth factor receptor-directed therapy
No prior anticancer murine or chimeric monoclonal antibody therapy
- Prior humanized monoclonal antibody therapy allowed
- No prior bevacizumab
- No other prior vascular endothelial growth factor-targeted therapy
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- More than 4 weeks since prior radiotherapy
- More than 28 days since prior major surgical procedure or open biopsy
- Recovered from all prior therapy
- Any number of prior standard or investigational regimens allowed
- No other concurrent investigational agents
- No other concurrent anticancer therapy
- No recent or concurrent thrombolytic agents
- No recent or concurrent full-dose warfarin except as required to maintain patency of preexisting, permanent indwelling IV catheters
No concurrent therapeutic heparin
- Concurrent prophylactic low-molecular weight heparin allowed
- No concurrent chronic daily aspirin (> 325 mg/day)
- No concurrent nonsteroidal anti-inflammatory medications known to inhibit platelet function
- No concurrent combination antiretroviral therapy for HIV-positive patients
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 |
---|---|
実験的:Arm A (cetuximab, bevacizumab, irinotecan)I
Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36; bevacizumab IV over 30-90 minutes on days 1*, 15, and 29 OR on days 1 and 22; and irinotecan IV over 30-90 minutes (at the same dose and schedule that the patient previously received) beginning on day 1. NOTE: *Bevacizumab is given on day 2 (instead of day 1) of course 1, and is given on day 1 of subsequent courses. |
相関研究
与えられた IV
他の名前:
与えられた IV
他の名前:
与えられた IV
他の名前:
|
実験的:Arm B (cetuximab and bevacizumab)
Patients receive cetuximab as in Arm A and bevacizumab IV over 30-90 minutes on days 1*, 15, and 29. NOTE: *Bevacizumab is given on day 2 (instead of day 1) of course 1, and is given on day 1 of subsequent courses. |
相関研究
与えられた IV
他の名前:
与えられた IV
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 |
時間枠 |
---|---|
Time to tumor progression
時間枠:Date of randomization to the date of either documentation of disease progression, or death, assessed up to 3 years
|
Date of randomization to the date of either documentation of disease progression, or death, assessed up to 3 years
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Objective response rate
時間枠:Up to 3 years
|
Up to 3 years
|
|
Overall survival
時間枠:Up to 3 years
|
Survival probabilities will be computed using Kaplan-Meier methods and compared using the log-rank test.
|
Up to 3 years
|
協力者と研究者
捜査官
- 主任研究者:Leonard Saltz、Memorial Sloan Kettering Cancer Center
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-2012-01445 (レジストリ識別子:CTRP (Clinical Trial Reporting Program))
- N01CM17101 (米国 NIH グラント/契約)
- 03-135 (その他の識別子:Memorial Sloan-Kettering Cancer Center)
- N01CM17105 (米国 NIH グラント/契約)
- N01CM17102 (米国 NIH グラント/契約)
- N01CM17103 (米国 NIH グラント/契約)
- MSKCC-03135
- NCI-6444
- CDR0000350086
- 6444 (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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