Cediranib Maleate With or Without Gefitinib in Treating Patients With Recurrent or Progressive Glioblastoma
Multi-Center, Randomized, Double-Blind Phase II Study Comparing Cediranib (AZD2171) Plus Gefitinib (Iressa, ZD1839) With Cediranib Plus Placebo in Subjects With Recurrent/Progressive Glioblastoma (DORIC Trial)
RATIONALE: Cediranib Maleate and gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether cediranib maleate given together with gefitinib is more effective than cediranib maleate given alone in treating patients with recurrent or progressive glioblastoma.
PURPOSE: This randomized phase II trial is studying the side effects of giving cediranib maleate together with gefitinib and to see how well it works compared with giving cediranib maleate together with a placebo in treating patients with recurrent or progressive glioblastoma.
調査の概要
詳細な説明
OBJECTIVES:
- To compare progression-free survival, overall survival, radiological response, and safety and tolerability of cediranib maleate in combination with gefitinib versus cediranib maleate in combination with a placebo in patients with recurrent or progressive glioblastoma following standard front-line treatment.
OUTLINE: This is a multicenter study.
Patients receive cediranib maleate and gefitinib or cediranib maleate and a placebo once daily on days 1-42. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Blood and tissue samples are collected from some patients for genetic profiling and biomarker analysis.
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
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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Birmingham、イギリス
- Queen Elizabeth Hospital
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Bristol、イギリス
- Bristol Haematology and Oncology Centre
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Cambridge、イギリス
- Addenbrooke's Hospital
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Guildford、イギリス
- Royal Surrey County Hospital
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Hull、イギリス
- Castle Hill Hospital
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London、イギリス
- Charing Cross Hospital
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Manchester、イギリス
- The Christie NHS Foundation Trust
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Southampton、イギリス
- Southampton General Hospital
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Sutton、イギリス
- Royal Marsden Hospital
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England
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London、England、イギリス、NW1 2BU
- University College Hospital
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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
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed glioblastoma
- Measurable disease by MRI
Completed standard first-line treatment for glioblastoma including surgery (unless not received due to anatomical location), radiotherapy and temozolomide (last dose given at least 28 days prior to enrollment)
- No other prior treatment for glioblastoma except Gliadel or steroids
Recurrent or progressive disease after standard first-line treatment
- No disease progression within 3 months of completion of radiotherapy
- No intra- or peri-tumoral hemorrhage
PATIENT CHARACTERISTICS:
- Karnofsky performance status 70-100%
- Mini-mental status score ≥ 15
- Life expectancy ≥ 12 weeks
- Serum bilirubin, ALT/AST, creatinine, and urine protein normal
- Adequate bone marrow reserve
- Not pregnant or nursing
- Normal ECG
- No history of familial long QT syndrome
- No absorption or swallowing difficulties
- No uncontrolled hypertension or cardiac ventricular arrhythmias
- No current or history of uncontrolled hypertension or requiring maximal doses of calcium channel blockers
- No severe or uncontrolled disease
- No history of lung disease
- No recent hemorrhage or hemoptysis
- No known hypersensitivity to cediranib maleate, gefitinib, or any excipients
- No history of other malignancies except adequately treated basal cell or squamous cell carcinoma or carcinoma in situ within the past 5 years, unless disease-free for 2 years with tissue diagnosis
- No known HIV positivity
- No known hepatitis B or C infection
- No unhealed surgical incision
- Not involved in planning or conducting this study
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered from prior anticancer therapy, including radiotherapy
- At least 3 months since prior cranial radiation
- At least 30 days since prior investigational drugs
- At least 28 days since prior craniotomy
- At least 2 weeks since prior enzyme-inducing antiepileptic drugs
- At least 2 weeks since prior and no concurrent dexamethasone (> 8 mg/day) or equivalent
- At least 14 days since prior major surgery or brain biopsy
- No concurrent steroids OR on stable dose 5 days prior to baseline MRI
- No other concurrent anticancer therapy, except for steroids (dexamethasone only)
- No previous enrollment on the current study
- No prior inhibitors of angiogenesis, EGFR, or downstream targets
- No prior radiosurgery or brachytherapy
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：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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アクティブコンパレータ：Cediranib & Gefitinib
Cediranib maleate 30mg od orally and gefitinib 500mg od orally.
Each cycle of treatment lasts 6 weeks.
Treatment will continue until confirmation of progression, patient decision or the development of unacceptable toxicity (if there is radiological progression only treatment can continue if the investigator has the opinion that the patient is receiving benefit.
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プラセボコンパレーター：Cediranbib & placebo
Cediranib maleate 30mg od orally and placebo 500mg od orally.
Each cycle of treatment lasts 6 weeks.
Treatment will continue until confirmation of progression, patient decision or the development of unacceptable toxicity (if there is radiological progression only treatment can continue if the investigator has the opinion that the patient is receiving benefit.
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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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Progression-free Survival
時間枠：from the date of randomisation to the date of first progression or death due to any cause, until 6 months from the date the last patient finished trial treatment (the day after the date that the last trial drug was taken)
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Progression free survival (PFS) defined as the time from the date of randomisation to the date of first progression or death due to any cause, whichever one comes first. The progression definition will be based on modified RANO criteria (Wen 2010), such that progression will be defined as the earliest time that at least one of the following occurs:
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from the date of randomisation to the date of first progression or death due to any cause, until 6 months from the date the last patient finished trial treatment (the day after the date that the last trial drug was taken)
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二次結果の測定
結果測定 |
時間枠 |
|---|---|
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Overall Survival
時間枠：from date of randomization to date of Death due to any cause.
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from date of randomization to date of Death due to any cause.
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Radiographic Response Rate
時間枠：from baseline scan to six week and 12 week scans
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from baseline scan to six week and 12 week scans
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Progression-free Survival Rate at 6 Months
時間枠：from the date of randomisation to 6 months
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from the date of randomisation to 6 months
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Steroid Use
時間枠：from randomization to first increase in dexamethasone dose
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from randomization to first increase in dexamethasone dose
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Time to Deterioration of Neurological Status
時間枠：from date of randomization to the date of first neurological status worsening in comparison to baseline (first of 2 confirmatory reports at 2 consecutive visits, 6 weeks apart) as assessed by the clinician, or until date of death, whichever is first.
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from date of randomization to the date of first neurological status worsening in comparison to baseline (first of 2 confirmatory reports at 2 consecutive visits, 6 weeks apart) as assessed by the clinician, or until date of death, whichever is first.
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Safety and Tolerability
時間枠：from date of randomisation to death
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from date of randomisation to death
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協力者と研究者
協力者
捜査官
- 主任研究者：Paul Mulholland, PhD, MRCP, MSC, MBBS、University College London Hospitals
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 (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
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