Cediranib in Combination With Lomustine Chemotherapy in Recurrent Glioblastoma (REGAL)

• Overall Survival (OS) [ Time Frame: Baseline through to date of death up to 25th April 2010 ] [ Designated as safety issue: No ]
  Number of months from randomisation to the date of death from any cause
• Response Rate [ Time Frame: Baseline at 6 weeks and then every 6 weeks to discontinuation ] [ Designated as safety issue: No ]

  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) [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
  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 [ Time Frame: Baseline to the date of first documented progression or date of death or study discontinuation, whichever came first, assed up to 2014-April-25 ] [ Designated as safety issue: No ]

  % change in mean daily steroid dose from baseline to progression (based on central review or death) or study discontinuation (whichever is earlier).

  If a patient had not progressed or discontinued the study, the data cut-off date was used (2010-04-25).

• Steroid Free Days [ Time Frame: Baseline to the date of first documented progression or date of death or study discontinuation, whichever came first, assed up to 2014-April-25 ] [ Designated as safety issue: No ]
  Number of days known not to have used any steroids prior to progression

• Assessment of overall survival and overall response rate, APF6 and steriod sparing effects of cediranib (either in monotherapy or in combination with oral lomustine) compared to oral lomustine alone [ Time Frame: Prior to first administration of investigational product (IP). After intake of IP, assessments taken every week for first 6 weeks, then every 3 weeks through study end ] [ Designated as safety issue: No ]
• Assessment of safety, tolerability and Quality of life of cediranib (either in monotherapy or in combination with oral lomustine) compared to oral lomustine alone [ Time Frame: Prior to first administration of investigational product (IP). After intake of IP, assessments taken every week for first 6 weeks, then every 3 weeks through study end ] [ Designated as safety issue: Yes ]

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.

• Drug: Cediranib
  30 mg/day, oral, until progression
• Drug: Cediranib
  20 mg/day, oral, until progression
• Drug: Lomustine Chemotherapy
  110 mg/m2 / Q6W, oral, until progression
• Drug: Placebo Cediranib
  Oral, until progression

• Experimental: Cediranib 30mg
  Cediranib 30mg
  Intervention: Drug: Cediranib
• Cediranib 20mg + lomustine
  Cediranib 20mg + lomustine
  Interventions:

  • Drug: Cediranib
  • Drug: Lomustine Chemotherapy
• Active Comparator: Lomustine and Placebo Cediranib
  Lomustine and Placebo Cediranib
  Interventions:

  • Drug: Lomustine Chemotherapy
  • Drug: Placebo Cediranib

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