Cediranib Maleate With or Without Gefitinib in Treating Patients With Recurrent or Progressive Glioblastoma
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.
Drug: cediranib maleate
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||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)|
- Progression-free Survival [ Time Frame: from the date of randomisation to the date of first progression or death due to any cause ]
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:
- Clinical deterioration
Failure to return for evaluation as a result of death or deteriorating condition
Or, by retrospective radiographic central review:
- Any new lesion
- Increase in ≥25% of sum of the products of perpendicular diameters of enhancing lesions compared with baseline scan, on stable or increasing doses of steroids (dexamethasone) compared to baseline (T1 post-contrast scan)
- Clear progression of non-measureable disease
- Significant increase in T2/FLAIR non-enhancing lesion - on stable or increasing steroids (dexamethasone) compared with baseline or best response not caused by co-morbid events.
- Overall Survival [ Time Frame: from date of randomization to date of Death due to any cause. ]
- Radiographic Response Rate [ Time Frame: from baseline scan to six week and 12 week scans ]
- Progression-free Survival Rate at 6 Months [ Time Frame: from the date of randomisation to 6 months ]
- Steroid Use [ Time Frame: from randomization to first increase in dexamethasone dose ]
- Time to Deterioration of Neurological Status [ Time Frame: 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. ]
- Safety and Tolerability [ Time Frame: from date of randomisation to death ]
|Study Start Date:||May 2011|
|Study Completion Date:||January 2014|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
Active Comparator: 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.
|Drug: cediranib maleate Drug: gefitinib|
Placebo Comparator: 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.
|Drug: cediranib maleate Drug: Placebo|
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01310855
|University College Hospital|
|London, England, United Kingdom, NW1 2BU|
|Queen Elizabeth Hospital|
|Birmingham, United Kingdom|
|Bristol Haematology and Oncology Centre|
|Bristol, United Kingdom|
|Cambridge, United Kingdom|
|Royal Surrey County Hospital|
|Guildford, United Kingdom|
|Castle Hill Hospital|
|Hull, United Kingdom|
|Charing Cross Hospital|
|London, United Kingdom|
|The Christie NHS Foundation Trust|
|Manchester, United Kingdom|
|Southampton General Hospital|
|Southampton, United Kingdom|
|Royal Marsden Hospital|
|Sutton, United Kingdom|
|Principal Investigator:||Paul Mulholland, PhD, MRCP, MSC, MBBS||University College London Hospitals|