GlioblastomaPhase 2NCT01310855
Cediranib Maleate With or Without Gefitinib in Treating Patients With Recurrent or Progressive Glioblastoma
A Phase 2 study testing cediranib maleate and gefitinib in people with Glioblastoma, run by University College, London at 10 sites in United Kingdom.
Trial summary
RATIONALE: Cediranib Maleate and gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether cediranib maleate given together with gefitinib is more effective than cediranib maleate given alone in treating… Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Glioblastoma
- What is being tested?
- cediranib maleate and gefitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 10 sitesUnited Kingdom
- Study dates
- May 2011to Jan 2014
- Phase
- Phase 2
- 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 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed glioblastoma
- Measurable disease by MRI
- Completed standard first-line treatment for glioblastoma including surgery (unless not received due to anatomical location), radiotherapy and temozolomide (last dose given at least 28 days prior to enrollment)
- No other prior treatment for glioblastoma except Gliadel or steroids
- Recurrent or progressive disease after standard first-line treatment
- No disease progression within 3 months of completion of radiotherapy
- No intra- or peri-tumoral hemorrhage
PATIENT CHARACTERISTICS:
- Karnofsky performance status 70-100%
- Mini-mental status score ≥ 15
- Life expectancy ≥ 12 weeks
- Serum bilirubin, ALT/AST, creatinine, and urine protein normal
- Adequate bone marrow reserve
- Not pregnant or nursing
- Normal ECG
- No history of familial long QT syndrome
- No absorption or swallowing difficulties
- No uncontrolled hypertension or cardiac ventricular arrhythmias
- No current or history of uncontrolled hypertension or requiring maximal doses of calcium channel blockers
- No severe or uncontrolled disease
- No history of lung disease
- No recent hemorrhage or hemoptysis
- No known hypersensitivity to cediranib maleate, gefitinib, or any excipients
- No history of other malignancies except adequately treated basal cell or squamous cell carcinoma or carcinoma in situ within the past 5 years, unless disease-free for 2 years with tissue diagnosis
- No known HIV positivity
- No known hepatitis B or C infection
- No unhealed surgical incision
- Not involved in planning or conducting this study
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered from prior anticancer therapy, including radiotherapy
- At least 3 months since prior cranial radiation
- At least 30 days since prior investigational drugs
- At least 28 days since prior craniotomy
- At least 2 weeks since prior enzyme-inducing antiepileptic drugs
- At least 2 weeks since prior and no concurrent dexamethasone (> 8 mg/day) or equivalent
- At least 14 days since prior major surgery or brain biopsy
- No concurrent steroids OR on stable dose 5 days prior to baseline MRI
- No other concurrent anticancer therapy, except for steroids (dexamethasone only)
- No previous enrollment on the current study
- No prior inhibitors of angiogenesis, EGFR, or downstream targets
- No prior radiosurgery or brachytherapy
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United Kingdom10 sites
Queen Elizabeth Hospital
Birmingham
Bristol Haematology and Oncology Centre
Bristol
Addenbrooke's Hospital
Cambridge
Royal Surrey County Hospital
Guildford
Castle Hill Hospital
Hull
University College Hospital
London, England, NW1 2BU
Charing Cross Hospital
London
The Christie NHS Foundation Trust
Manchester
Southampton General Hospital
Southampton
Royal Marsden Hospital
Sutton
About this study
Official title: Multi-Center, Randomized, Double-Blind Phase II Study Comparing Cediranib (AZD2171) Plus Gefitinib (Iressa, ZD1839) With Cediranib Plus Placebo in Subjects With Recurrent/Progressive Glioblastoma (DORIC Trial)
RATIONALE: Cediranib Maleate and gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether cediranib maleate given together with gefitinib is more effective than cediranib maleate given alone in treating patients with recurrent or progressive glioblastoma.
PURPOSE: This randomized phase II trial is studying the side effects of giving cediranib maleate together with gefitinib and to see how well it works compared with giving cediranib maleate together with a placebo in treating patients with recurrent or progressive glioblastoma.
Read the detailed description
OBJECTIVES:
- To compare progression-free survival, overall survival, radiological response, and safety and tolerability of cediranib maleate in combination with gefitinib versus cediranib maleate in combination with a placebo in patients with recurrent or progressive glioblastoma following standard front-line treatment.
OUTLINE: This is a multicenter study.
Patients receive cediranib maleate and gefitinib or cediranib maleate and a placebo once daily on days 1-42. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Blood and tissue samples are collected from some patients for genetic profiling and biomarker analysis.
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
- Conditions
- Glioblastoma
- Being tested
- cediranib maleate, gefitinib, Placebo
- Keywords
- adult giant cell glioblastoma, adult glioblastoma, adult gliosarcoma, recurrent adult brain tumor
- Medical subject headings
- Glioblastoma, Gliosarcoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cediranib maleateDrug
gefitinibDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Cediranib & Gefitinib | Active comparator | Cediranib maleate 30mg od orally and gefitinib 500mg od orally. Each cycle of treatment lasts 6 weeks. Treatment will continue until confirmation of progression, patient decision or the development of unacceptable toxicity (if there is radiological progression only treatment can continue if the investigator has the opinion that the patient is receiving benefit. Receives: Drug: cediranib maleate; Drug: gefitinib |
| Cediranbib & placebo | Placebo comparator | Cediranib maleate 30mg od orally and placebo 500mg od orally. Each cycle of treatment lasts 6 weeks. Treatment will continue until confirmation of progression, patient decision or the development of unacceptable toxicity (if there is radiological progression only treatment can continue if the investigator has the opinion that the patient is receiving benefit. Receives: Drug: cediranib maleate; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival
Progression free survival (PFS) defined as the time from the date of randomisation to the date of first progression or death due to any cause, whichever one comes first.
The progression definition will be based on modified RANO criteria (Wen 2010), such that progression will be defined as the earliest time that at least one of the following occurs:
- Clinical deterioration
- Failure to return for evaluation as a result of death or deteriorating condition Or, by retrospective radiographic central review:
- Any new lesion
- Increase in ≥25% of sum of the products of perpendicular diameters of enhancing lesions compared with baseline scan, on stable or increasing doses of steroids (dexamethasone) compared to baseline (T1 post-contrast scan)
- Clear progression of non-measureable disease
- Significant increase in T2/FLAIR non-enhancing lesion - on stable or increasing steroids (dexamethasone) compared with baseline or best response not caused by co-morbid events.
Measured: from the date of randomisation to the date of first progression or death due to any cause, until 6 months from the date the last patient finished trial treatment (the day after the date that the last trial drug was taken)
Secondary outcomes (6)
Overall Survival
Measured: from date of randomization to date of Death due to any cause.
Radiographic Response Rate
Measured: from baseline scan to six week and 12 week scans
Progression-free Survival Rate at 6 Months
Measured: from the date of randomisation to 6 months
Steroid Use
Measured: from randomization to first increase in dexamethasone dose
Time to Deterioration of Neurological Status
Measured: from date of randomization to the date of first neurological status worsening in comparison to baseline (first of 2 confirmatory reports at 2 consecutive visits, 6 weeks apart) as assessed by the clinician, or until date of death, whichever is first.
Safety and Tolerability
Measured: from date of randomisation to death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2011 (estimated)
- Study startMay 2011
- Primary completionMay 2013
- Study completionJan 2014
Why it stopped: closed to recruitment early due to AstraZeneca not developing cediranib further
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 GlioblastomaStudies of the same condition, open and under way.
- More trials run by University College, LondonThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Paul Mulholland, PhD, MRCP, MSC, MBBS, Principal investigator, University College London Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01310855
- Sponsor's protocol ID
- CDR0000696313
- Other IDs
- UCL-10/0035, ZENECA-ISSRECE00002, EUDRACT-2010-021531-13, CRUKE/10/044
- Status last verified
- May 2017
- First submitted
- 5 Mar 2011
- Last updated
- 31 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Brown N, McBain C, Nash S, Hopkins K, Sanghera P, Saran F, Phillips M, Dungey F, Clifton-Hadley L, Wanek K, Krell D, Jeffries S, Khan I, Smith P, Mulholland P. Multi-Center Randomized Phase II Study Comparing Cediranib plus Gefitinib with Cediranib plus Placebo in Subjects with Recurrent/Progressive Glioblastoma. PLoS One. 2016 May 27;11(5):e0156369. doi: 10.1371/journal.pone.0156369. eCollection 2016.
PubMed 27232884
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-Center, Randomized, Double-Blind Phase II Study Comparing Cediranib (AZD2171) Plus Gefitinib (Iressa, ZD1839) With Cediranib Plus Placebo in Subjects With Recurrent/Progressive Glioblastoma (DORIC Trial)
- ClinicalTrials.gov ID
- NCT01310855
- Acronym / sponsor ID
- CDR0000696313
- Conditions
- Glioblastoma
- Keywords
- adult giant cell glioblastoma, adult glioblastoma, adult gliosarcoma, recurrent adult brain tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: closed to recruitment early due to AstraZeneca not developing cediranib further
- Enrolment
- 38 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- May 2011
- Primary completion
- May 2013 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 9 Mar 2011 (estimated)
- Results
- Posted 27 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Cediranib Maleate and gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether cediranib maleate given together with gefitinib is more effective than cediranib maleate given alone in treating patients with recurrent or progressive glioblastoma.
PURPOSE: This randomized phase II trial is studying the side effects of giving cediranib maleate together with gefitinib and to see how well it works compared with giving cediranib maleate together with a placebo in treating patients with recurrent or progressive glioblastoma.
Detailed description
OBJECTIVES:
- To compare progression-free survival, overall survival, radiological response, and safety and tolerability of cediranib maleate in combination with gefitinib versus cediranib maleate in combination with a placebo in patients with recurrent or progressive glioblastoma following standard front-line treatment.
OUTLINE: This is a multicenter study.
Patients receive cediranib maleate and gefitinib or cediranib maleate and a placebo once daily on days 1-42. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Blood and tissue samples are collected from some patients for genetic profiling and biomarker analysis.
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cediranib & Gefitinib | Active comparator | Drug: cediranib maleate, Drug: gefitinibCediranib maleate 30mg od orally and gefitinib 500mg od orally. Each cycle of treatment lasts 6 weeks. Treatment will continue until confirmation of progression, patient decision or the development of unacceptable toxicity (if there is radiological progression only treatment can continue if the investigator has the opinion that the patient is receiving benefit. |
| Cediranbib & placebo | Placebo comparator | Drug: cediranib maleate, Drug: PlaceboCediranib maleate 30mg od orally and placebo 500mg od orally. Each cycle of treatment lasts 6 weeks. Treatment will continue until confirmation of progression, patient decision or the development of unacceptable toxicity (if there is radiological progression only treatment can continue if the investigator has the opinion that the patient is receiving benefit. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| cediranib maleate | Drug | Cediranbib & placebo, Cediranib & Gefitinib |
| gefitinib | Drug | Cediranib & Gefitinib |
| Placebo | Drug | Cediranbib & placebo |
Primary outcome
Progression-free Survival
Time frame: from the date of randomisation to the date of first progression or death due to any cause, until 6 months from the date the last patient finished trial treatment (the day after the date that the last trial drug was taken)
Progression free survival (PFS) defined as the time from the date of randomisation to the date of first progression or death due to any cause, whichever one comes first. The progression definition will be based on modified RANO criteria (Wen 2010), such that progression will be defined as the earliest time that at least one of the following occurs: 1. Clinical deterioration 2. Failure to return for evaluation as a result of death or deteriorating condition Or, by retrospective radiographic central review: 3. Any new lesion 4. Increase in ≥25% of sum of the products of perpendicular diameters of enhancing lesions compared with baseline scan, on stable or increasing doses of steroids (dexamethasone) compared to baseline (T1 post-contrast scan) 5. Clear progression of non-measureable disease 6. Significant increase in T2/FLAIR non-enhancing lesion - on stable or increasing steroids (dexamethasone) compared with baseline or best response not caused by co-morbid events.
6 secondary outcomes
Overall Survival
Time frame: from date of randomization to date of Death due to any cause.
Radiographic Response Rate
Time frame: from baseline scan to six week and 12 week scans
Progression-free Survival Rate at 6 Months
Time frame: from the date of randomisation to 6 months
Steroid Use
Time frame: from randomization to first increase in dexamethasone dose
Time to Deterioration of Neurological Status
Time frame: from date of randomization to the date of first neurological status worsening in comparison to baseline (first of 2 confirmatory reports at 2 consecutive visits, 6 weeks apart) as assessed by the clinician, or until date of death, whichever is first.
Safety and Tolerability
Time frame: from date of randomisation to death
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27232884Brown N, McBain C, Nash S, Hopkins K, Sanghera P, Saran F, Phillips M, Dungey F, Clifton-Hadley L, Wanek K, Krell D, Jeffries S, Khan I, Smith P, Mulholland P. Multi-Center Randomized Phase II Study Comparing Cediranib plus Gefitinib with Cediranib plus Placebo in Subjects with Recurrent/Progressive Glioblastoma. PLoS One. 2016 May 27;11(5):e0156369. doi: 10.1371/journal.pone.0156369. eCollection 2016.
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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.
Paul Mulholland, PhD, MRCP, MSC, MBBS principal investigator
University College London Hospitals
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cediranib maleate and gefitinib in people with Glioblastoma, run by University College, London at 10 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: stopped early, as of the sponsor's last update on 31 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United Kingdom. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 27 Jan 2017). 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 (time frame: from the date of randomisation to the date of first progression or death due to any cause, until 6 months from the date the last patient finished trial treatment (the day after the date that the last trial drug was taken)). 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 NCT01310855, 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 31 May 2017.