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

November 7, 2016 updated by: AstraZeneca

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

423

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Camperdown, Australia
        • Research Site
      • Heidelberg, Australia
        • Research Site
      • Nedlands, Australia
        • Research Site
      • Parkville, Australia
        • Research Site
      • St Leonards, Australia
        • Research Site
      • Woodville, Australia
        • Research Site
  • Austria
      • Graz, Austria
        • Research Site
  • Belgium
      • Brussels (Anderlecht), Belgium
        • Research Site
      • Brussels (Jette), Belgium
        • Research Site
      • Brussels (Woluwé-St-Lambert), Belgium
        • Research Site
      • Leuven, Belgium
        • Research Site
  • Canada
    • Alberta
      • Calgary, Alberta, Canada
        • Research Site
    • Ontario
      • Toronto, Ontario, Canada
        • Research Site
    • Quebec
      • Montreal, Quebec, Canada
        • Research Site
  • Czech Republic
      • Liberec, Czech Republic
        • Research Site
  • France
      • Bobigny, France
        • Research Site
      • Marseille, France
        • Research Site
      • Paris cedex 13, France
        • Research Site
      • Rennes, France
        • Research Site
      • Saint Herblain, France
        • Research Site
      • Villejuif, France
        • Research Site
  • Germany
      • Berlin, Germany
        • Research Site
      • Bielefeld, Germany
        • Research Site
      • Dresden, Germany
        • Research Site
      • Düsseldorf, Germany
        • Research Site
      • Göttingen, Germany
        • Research Site
      • Hannover, Germany
        • Research Site
      • Heidelberg, Germany
        • Research Site
      • Kiel, Germany
        • Research Site
      • Leipzig, Germany
        • Research Site
      • Nordhausen, Germany
        • Research Site
      • Regensburg, Germany
        • Research Site
  • Netherlands
      • Amsterdam, Netherlands
        • Research Site
      • Den Haag, Netherlands
        • Research Site
      • Groningen, Netherlands
        • Research Site
      • Maastricht, Netherlands
        • Research Site
      • Rotterdam, Netherlands
        • Research Site
  • United Kingdom
      • Glasgow, United Kingdom
        • Research Site
      • London, United Kingdom
        • Research Site
      • Manchester, United Kingdom
        • Research Site
      • Sutton, United Kingdom
        • Research Site
  • United States
    • Alabama
      • Birmingham, Alabama, United States
        • Research Site
    • Arizona
      • Pheonix, Arizona, United States
        • Research Site
    • California
      • Los Angeles, California, United States
        • Research Site
    • Connecticut
      • New Haven, Connecticut, United States
        • Research Site
    • Florida
      • Gainesville, Florida, United States
        • Research Site
      • Jacksonville, Florida, United States
        • Research Site
    • Illinois
      • Chicago, Illinois, United States
        • Research Site
      • Evanston, Illinois, United States
        • Research Site
    • Kansas
      • Kansas City, Kansas, United States
        • Research Site
    • Massachusetts
      • Boston, Massachusetts, United States
        • Research Site
    • Michigan
      • Detroit, Michigan, United States
        • Research Site
    • New York
      • Amherst, New York, United States
        • Research Site
      • New York, New York, United States
        • Research Site
    • Ohio
      • Cincinnati, Ohio, United States
        • Research Site
      • Cleveland, Ohio, United States
        • Research Site
      • Columbus, Ohio, United States
        • Research Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
        • Research Site
      • Pittsburgh, Pennsylvania, United States
        • Research Site
    • Texas
      • Houston, Texas, United States
        • Research Site
    • Washington
      • Seattle, Washington, United States
        • Research Site
    • West Virginia
      • Morgantown, West Virginia, United States
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Cediranib 30mg
Drug: Cediranib
30 mg/day, oral, until progression
Drug: Cediranib
20 mg/day, oral, until progression
OTHER: Cediranib 20mg + lomustine
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
ACTIVE_COMPARATOR: Lomustine and Placebo Cediranib
Drug: Lomustine Chemotherapy
110 mg/m2 / Q6W, oral, until progression
Drug: Placebo Cediranib
Oral, until progression

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: 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.
Baseline at 6 weeks and then every 6 weeks to discontinuation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Baseline through to date of death up to 25th April 2010
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
Time Frame: 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.
Baseline at 6 weeks and then every 6 weeks to discontinuation
Alive and Progression Free Rate at 6 Months (APF6)
Time Frame: 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.
6 Months
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
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
Time Frame: 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
Baseline to the date of first documented progression or date of death or study discontinuation, whichever came first, assessed up to 2014-April-25

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Investigators

  • Principal Investigator: Tracy Batchelor, MD, MPH, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2008

Primary Completion (ACTUAL)

April 1, 2010

Study Completion (ACTUAL)

September 1, 2016

Study Registration Dates

First Submitted

October 20, 2008

First Submitted That Met QC Criteria

October 21, 2008

First Posted (ESTIMATE)

October 22, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

December 28, 2016

Last Update Submitted That Met QC Criteria

November 7, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D8480C00055

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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