Cediranib in Combination With Lomustine Chemotherapy in Recurrent Glioblastoma

Phase 3

Completed

• Conditions: Recurrent Glioblastoma
• Interventions: Drug: Cediranib; Drug: Placebo Cediranib; Drug: Lomustine Chemotherapy

• Registration Number: NCT00777153
• Lead Sponsor: AstraZeneca

Brief Summary

The purpose of this study is to see how effective cediranib is in treating a brain tumour called recurrent glioblastoma. Two drugs are being tested in this study. Lomustine is an approved oral chemotherapy that belongs to the class of drugs called alkylating agents. Cediranib is a new drug that has not yet been approved for this disease. This study will compare the use of lomustine with cediranib, cediranib alone or lomustine with placebo ("inactive substance") to see whether the combination or cediranib alone will be more effective than the chemotherapy alone (lomustine) in preventing the growth of cancer cells.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-10
• Study First Submitted: 2008-10-20
• Study First Submitted QC: 2008-10-21
• Study First Posted: 2008-10-22
• Primary Completion: 2010-04
• Disposition First Submitted: 2011-04-06
• Disposition First Submitted QC: 2011-04-06
• Disposition First Posted: 2011-04-12
• Results First Submitted: 2012-04-03
• Results First Submitted QC: 2012-11-21
• Results First Posted: 2012-12-21
• Study Completion: 2016-09
• Status Verified: 2016-10
• Last Update Submitted: 2016-11-07
• Last Update Posted: 2016-12-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 423

Inclusion Criteria

• Confirmation of recurrent glioblastoma
• Life expectancy ≥ 12 weeks
• Received only one prior systemic chemotherapy regimen and this regimen must contain temozolomide

Exclusion Criteria

• Patients on enzyme-inducing anti-epileptic drugs within 3 weeks prior to randomisation
• Poorly controlled hypertension
• Previous anti-angiogenesis (eg bevacizumab, sorafenib, sunitinib) therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lomustine and Placebo Cediranib	Placebo Cediranib	Lomustine and Placebo Cediranib
Cediranib 20mg + lomustine	Cediranib	Cediranib 20mg + lomustine
Cediranib 20mg + lomustine	Lomustine Chemotherapy	Cediranib 20mg + lomustine
Cediranib 30mg	Cediranib	Cediranib 30mg
Lomustine and Placebo Cediranib	Lomustine Chemotherapy	Lomustine and Placebo Cediranib

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	Baseline at 6 weeks and then every 6 weeks to discontinuation	For patients with measurable disease at entry (at least one lesion that has a shortest diameter; ≥10 mm at baseline on 2 axial slices), PFS will be defined as the earliest time that: 1. The sum of the products of the largest perpendicular diameters of contrast enhancement for all lesions has increased by a greater than or equal to 25% in comparison to the nadir scan as long as the shortest diameter is ≥15 mm. If the dose of steroids has been reduced within the 10 days prior to the scan being conducted, progression will be based on a follow-up scan performed after the dose of steroids has been stabilized for 10 days.; 2. The patient has died from any cause.; 3. A new lesion is detected that is outside the original tumor volume and has a shortest diameter ≥10 mm.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Baseline through to date of death up to 25th April 2010	Number of months from randomisation to the date of death from any cause
Response Rate	Baseline at 6 weeks and then every 6 weeks to discontinuation	An individual visit response of PR was defined as a greater than or equal to 50% reduction in the sum of the products of the largest perpendicular diameters of contrast enhancement for all lesions compared to baseline as long as the steroid dose has not been increased within the previous 10 days and no new lesions are present.; An individual visit response of CR was defined as the complete disappearance of all tumor on MRI scan.
Alive and Progression Free Rate at 6 Months (APF6)	6 Months	Proportion of patients alive and progression free at 6 months (based on central review) as estimated from Kaplan-Meier techniques. Values are percentages.
Daily Steroid Dose	Baseline to the date of first documented progression or date of death or study discontinuation, whichever came first, assed up to 2014-April-25	The mean steroid dosage prior to treatment will be considered as the patient's baseline. The percent change in average daily steroid dosage from baseline is calculated by following formula: PC = (md - bm)/bm\*100; where PC is the percent change in average daily steroid dosage from baseline; md the mean daily steroid dosage recorded from the first day of therapy to progression; and bm the baseline mean.
Steroid Free Days	Baseline to the date of first documented progression or date of death or study discontinuation, whichever came first, assessed up to 2014-April-25	Number of days known not to have used any steroids prior to progression

Trial Locations

Locations (1)

Research Site; 🇬🇧 Sutton, United Kingdom