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Cediranib Maleate With or Without Gefitinib in Treating Patients With Recurrent or Progressive Glioblastoma

Primary Purpose

Glioblastoma

Status
Terminated
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
cediranib maleate
gefitinib
Placebo
Sponsored by
University College, London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring adult giant cell glioblastoma, adult glioblastoma, adult gliosarcoma, recurrent adult brain tumor

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University College Hospital
  • Queen Elizabeth Hospital
  • Bristol Haematology and Oncology Centre
  • Addenbrooke's Hospital
  • Royal Surrey County Hospital
  • Castle Hill Hospital
  • Charing Cross Hospital
  • The Christie NHS Foundation Trust
  • Southampton General Hospital
  • Royal Marsden Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Cediranib & Gefitinib

Cediranbib & placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Overall Survival
Radiographic Response Rate
Progression-free Survival Rate at 6 Months
Steroid Use
Time to Deterioration of Neurological Status
Safety and Tolerability

Full Information

First Posted
March 5, 2011
Last Updated
May 2, 2017
Sponsor
University College, London
Collaborators
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT01310855
Brief Title
Cediranib Maleate With or Without Gefitinib in Treating Patients With Recurrent or Progressive Glioblastoma
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)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Terminated
Why Stopped
closed to recruitment early due to AstraZeneca not developing cediranib further
Study Start Date
May 2011 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
January 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University College, London
Collaborators
AstraZeneca

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma
Keywords
adult giant cell glioblastoma, adult glioblastoma, adult gliosarcoma, recurrent adult brain tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
38 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cediranib & Gefitinib
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Cediranbib & placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
cediranib maleate
Intervention Type
Drug
Intervention Name(s)
gefitinib
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Progression-free Survival
Description
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.
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)
Secondary Outcome Measure Information:
Title
Overall Survival
Time Frame
from date of randomization to date of Death due to any cause.
Title
Radiographic Response Rate
Time Frame
from baseline scan to six week and 12 week scans
Title
Progression-free Survival Rate at 6 Months
Time Frame
from the date of randomisation to 6 months
Title
Steroid Use
Time Frame
from randomization to first increase in dexamethasone dose
Title
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.
Title
Safety and Tolerability
Time Frame
from date of randomisation to death

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Mulholland, PhD, MRCP, MSC, MBBS
Organizational Affiliation
University College London Hospitals
Official's Role
Principal Investigator
Facility Information:
Facility Name
University College Hospital
City
London
State/Province
England
ZIP/Postal Code
NW1 2BU
Country
United Kingdom
Facility Name
Queen Elizabeth Hospital
City
Birmingham
Country
United Kingdom
Facility Name
Bristol Haematology and Oncology Centre
City
Bristol
Country
United Kingdom
Facility Name
Addenbrooke's Hospital
City
Cambridge
Country
United Kingdom
Facility Name
Royal Surrey County Hospital
City
Guildford
Country
United Kingdom
Facility Name
Castle Hill Hospital
City
Hull
Country
United Kingdom
Facility Name
Charing Cross Hospital
City
London
Country
United Kingdom
Facility Name
The Christie NHS Foundation Trust
City
Manchester
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
Country
United Kingdom
Facility Name
Royal Marsden Hospital
City
Sutton
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
27232884
Citation
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.
Results Reference
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Cediranib Maleate With or Without Gefitinib in Treating Patients With Recurrent or Progressive Glioblastoma

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