Cediranib in Combination With Lomustine Chemotherapy in Recurrent Glioblastoma

Study Overview
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Brief Summary
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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.

Official Title
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A Phase III, Randomised, Parallel Group, Multi-Centre Study in Recurrent Glioblastoma Patients to Compare the Efficacy of Cediranib [RECENTIN™, AZD2171] Monotherapy and the Combination of Cediranib With Lomustine to the Efficacy of Lomustine Alone

Conditions
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Recurrent Glioblastoma

Intervention / Treatment
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* Drug: Cediranib
* Drug: Cediranib
* Drug: Lomustine Chemotherapy
* Drug: Placebo Cediranib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cediranib 30mg<br>Cediranib 30mg | Drug: Cediranib<br>* 30 mg/day, oral, until progression<br>|
| Other: Cediranib 20mg + lomustine<br>Cediranib 20mg + lomustine | Drug: Cediranib<br>* 20 mg/day, oral, until progression<br>Drug: Lomustine Chemotherapy<br>* 110 mg/m2 / Q6W, oral, until progression<br>|
| Active Comparator: Lomustine and Placebo Cediranib<br>Lomustine and Placebo Cediranib | Drug: Lomustine Chemotherapy<br>* 110 mg/m2 / Q6W, oral, until progression<br>Drug: Placebo Cediranib<br>* Oral, until progression<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | 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: 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. The patient has died from any cause. A new lesion is detected that is outside the original tumor volume and has a shortest diameter ≥10 mm. | Baseline at 6 weeks and then every 6 weeks to discontinuation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Number of months from randomisation to the date of death from any cause | Baseline through to date of death up to 25th April 2010 | 
| Response Rate | 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. | Baseline at 6 weeks and then every 6 weeks to discontinuation | 
| Alive and Progression Free Rate at 6 Months (APF6) | Proportion of patients alive and progression free at 6 months (based on central review) as estimated from Kaplan-Meier techniques. Values are percentages. | 6 Months | 
| Daily Steroid Dose | 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. | Baseline to the date of first documented progression or date of death or study discontinuation, whichever came first, assed up to 2014-April-25 | 
| Steroid Free Days | Number of days known not to have used any steroids prior to progression | Baseline to the date of first documented progression or date of death or study discontinuation, whichever came first, assessed up to 2014-April-25 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Tumour, Advanced Solid Tumour, GBM, Glioblastoma