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.
연구 개요
상세 설명
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.
연구 유형
등록 (실제)
단계
- 2 단계
연락처 및 위치
연구 장소
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Birmingham, 영국
- Queen Elizabeth Hospital
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Bristol, 영국
- Bristol Haematology and Oncology Centre
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Cambridge, 영국
- Addenbrooke's Hospital
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Guildford, 영국
- Royal Surrey County Hospital
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Hull, 영국
- Castle Hill Hospital
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London, 영국
- Charing Cross Hospital
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Manchester, 영국
- The Christie NHS Foundation Trust
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Southampton, 영국
- Southampton General Hospital
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Sutton, 영국
- Royal Marsden Hospital
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England
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London, England, 영국, NW1 2BU
- University College Hospital
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 네 배로
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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활성 비교기: 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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위약 비교기: 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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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Progression-free Survival
기간: 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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2차 결과 측정
결과 측정 |
기간 |
|---|---|
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Overall Survival
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: from date of randomisation to death
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from date of randomisation to death
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공동 작업자 및 조사자
협력자
수사관
- 수석 연구원: Paul Mulholland, PhD, MRCP, MSC, MBBS, University College London Hospitals
간행물 및 유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- CDR0000696313
- UCL-10/0035
- ZENECA-ISSRECE00002
- EUDRACT-2010-021531-13
- CRUKE/10/044
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