Recurrent GlioblastomaPhase 3REGALNCT00777153
Cediranib in Combination With Lomustine Chemotherapy in Recurrent Glioblastoma
A Phase 3 study testing Cediranib and Lomustine Chemotherapy in people with Recurrent Glioblastoma, run by AstraZeneca at 62 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Recurrent Glioblastoma
- What is being tested?
- Cediranib and Lomustine Chemotherapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 423 participants
- Where
- 62 sitesin 10 countries
- Study dates
- Oct 2008to Sep 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmation of recurrent glioblastoma
- Life expectancy ≥ 12 weeks
- Received only one prior systemic chemotherapy regimen and this regimen must contain temozolomide
Who cannot join
- Patients on enzyme-inducing anti-epileptic drugs within 3 weeks prior to randomisation
- Poorly controlled hypertension
- Previous anti-angiogenesis (eg bevacizumab, sorafenib, sunitinib) therapy
Trial locations and contacts
62 sites in 10 countries.
62 sites in 10 countries
United States21 sites
Research Site
Amherst, New York
Research Site
Birmingham, Alabama
Research Site
Boston, Massachusetts
Research Site
Chicago, Illinois
Research Site
Cincinnati, Ohio
Research Site
Cleveland, Ohio
Research Site
Columbus, Ohio
Research Site
Detroit, Michigan
Research Site
Evanston, Illinois
Research Site
Gainesville, Florida
Research Site
Houston, Texas
Research Site
Jacksonville, Florida
Research Site
Kansas City, Kansas
Research Site
Los Angeles, California
Research Site
Morgantown, West Virginia
Research Site
New Haven, Connecticut
Research Site
New York, New York
Research Site
Pheonix, Arizona
Research Site
Philadelphia, Pennsylvania
Research Site
Pittsburgh, Pennsylvania
Research Site
Seattle, Washington
Germany11 sites
Research Site
Berlin
Research Site
Bielefeld
Research Site
Dresden
Research Site
Düsseldorf
Research Site
Göttingen
Research Site
Hanover
Research Site
Heidelberg
Research Site
Kiel
Research Site
Leipzig
Research Site
Nordhausen
Research Site
Regensburg
Australia6 sites
Research Site
Camperdown
Research Site
Heidelberg
Research Site
Nedlands
Research Site
Parkville
Research Site
St Leonards
Research Site
Woodville
France6 sites
Research Site
Bobigny
Research Site
Marseille
Research Site
Paris
Research Site
Rennes
Research Site
Saint-Herblain
Research Site
Villejuif
Netherlands5 sites
Research Site
Amsterdam
Research Site
Groningen
Research Site
Maastricht
Research Site
Rotterdam
Research Site
The Hague
Belgium4 sites
Research Site
Brussels (Anderlecht)
Research Site
Brussels (Jette)
Research Site
Brussels (Woluwé-St-Lambert)
Research Site
Leuven
United Kingdom4 sites
Research Site
Glasgow
Research Site
London
Research Site
Manchester
Research Site
Sutton
Canada3 sites
Research Site
Calgary, Alberta
Research Site
Montreal, Quebec
Research Site
Toronto, Ontario
About this study
Official title: 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.
- Conditions
- Recurrent Glioblastoma
- Being tested
- Cediranib, Lomustine Chemotherapy, Placebo Cediranib
- Keywords
- Cancer, Tumour, Advanced Solid Tumour, GBM, Glioblastoma
- Medical subject headings
- Glioblastoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CediranibDrug
30 mg/day, oral, until progression
CediranibDrug
20 mg/day, oral, until progression
Lomustine ChemotherapyDrug
110 mg/m2 / Q6W, oral, until progression
Placebo CediranibDrug
Oral, until progression
| Study group | Role | What they receive |
|---|---|---|
| Cediranib 30mg | Experimental | Cediranib 30mg Receives: Drug: Cediranib |
| Cediranib 20mg + lomustine | Other | Cediranib 20mg + lomustine Receives: Drug: Cediranib; Drug: Lomustine Chemotherapy |
| Lomustine and Placebo Cediranib | Active comparator | Lomustine and Placebo Cediranib Receives: Drug: Lomustine Chemotherapy; Drug: Placebo Cediranib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline at 6 weeks and then every 6 weeks to discontinuation
Secondary outcomes (5)
Overall Survival (OS)
Number of months from randomisation to the date of death from any cause
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: Baseline to the date of first documented progression or date of death or study discontinuation, whichever came first, assessed up to 2014-April-25
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2008 (estimated)
- Study startOct 2008
- Primary completionApr 2010
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Recurrent GlioblastomaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 423 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jane Robertson, Study director, AstraZenecaTracy Batchelor, MD, MPH, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00777153
- Sponsor's protocol ID
- D8480C00055
- Acronym
- REGAL
- Status last verified
- Oct 2016
- First submitted
- 20 Oct 2008
- Last updated
- 28 Dec 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Batchelor TT, Mulholland P, Neyns B, Nabors LB, Campone M, Wick A, Mason W, Mikkelsen T, Phuphanich S, Ashby LS, Degroot J, Gattamaneni R, Cher L, Rosenthal M, Payer F, Jurgensmeier JM, Jain RK, Sorensen AG, Xu J, Liu Q, van den Bent M. Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. J Clin Oncol. 2013 Sep 10;31(26):3212-8. doi: 10.1200/JCO.2012.47.2464. Epub 2013 Aug 12.
PubMed 23940216
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00777153
- Acronym / sponsor ID
- REGAL / D8480C00055
- Conditions
- Recurrent Glioblastoma
- Keywords
- Cancer, Tumour, Advanced Solid Tumour, GBM, Glioblastoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 423 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- Oct 2008
- Primary completion
- Apr 2010 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 22 Oct 2008 (estimated)
- Results
- Posted 21 Dec 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cediranib 30mg | Experimental | Drug: CediranibCediranib 30mg |
| Cediranib 20mg + lomustine | Other | Drug: Cediranib, Drug: Lomustine ChemotherapyCediranib 20mg + lomustine |
| Lomustine and Placebo Cediranib | Active comparator | Drug: Lomustine Chemotherapy, Drug: Placebo CediranibLomustine and Placebo Cediranib |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Confirmation of recurrent glioblastoma
- Life expectancy ≥ 12 weeks
- Received only one prior systemic chemotherapy regimen and this regimen must contain temozolomide
Key exclusion criteria (3 listed)
- Patients on enzyme-inducing anti-epileptic drugs within 3 weeks prior to randomisation
- Poorly controlled hypertension
- Previous anti-angiogenesis (eg bevacizumab, sorafenib, sunitinib) therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cediranib30 mg/day, oral, until progression | Drug | Cediranib 30mg |
| Cediranib20 mg/day, oral, until progression | Drug | Cediranib 20mg + lomustine |
| Lomustine Chemotherapy110 mg/m2 / Q6W, oral, until progression | Drug | Cediranib 20mg + lomustine, Lomustine and Placebo Cediranib |
| Placebo CediranibOral, until progression | Drug | Lomustine and Placebo Cediranib |
Primary outcome
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.
5 secondary outcomes
Overall Survival (OS)
Time frame: 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
Alive and Progression Free Rate at 6 Months (APF6)
Time frame: 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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23940216Batchelor TT, Mulholland P, Neyns B, Nabors LB, Campone M, Wick A, Mason W, Mikkelsen T, Phuphanich S, Ashby LS, Degroot J, Gattamaneni R, Cher L, Rosenthal M, Payer F, Jurgensmeier JM, Jain RK, Sorensen AG, Xu J, Liu Q, van den Bent M. Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. J Clin Oncol. 2013 Sep 10;31(26):3212-8. doi: 10.1200/JCO.2012.47.2464. Epub 2013 Aug 12.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jane Robertson study director
AstraZeneca
Tracy Batchelor, MD, MPH principal investigator
Massachusetts General Hospital
62 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cediranib and Lomustine Chemotherapy in people with Recurrent Glioblastoma, run by AstraZeneca at 62 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 62 sites in United States, Germany, Australia, France, Netherlands and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) (time frame: Baseline at 6 weeks and then every 6 weeks to discontinuation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00777153, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2016.