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

This study has been terminated.
(closed to recruitment early due to AstraZeneca not developing cediranib further)
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT01310855
First received: March 5, 2011
Last updated: December 2, 2016
Last verified: December 2016

March 5, 2011
December 2, 2016
May 2011
May 2013   (Final data collection date for 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 ]

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.
Progression-free Survival
Complete list of historical versions of study NCT01310855 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Overall Survival
  • Radiographic Response Rate
  • Progression-free Survival Rate at 6 Months
  • Steroid Use
  • Time to Deterioration of Neurological Status
  • Safety and Tolerability
Not Provided
Not Provided
 
Cediranib Maleate With or Without Gefitinib in Treating Patients With Recurrent or Progressive Glioblastoma
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.

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.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Glioblastoma
  • Drug: cediranib maleate
  • Drug: gefitinib
  • Drug: Placebo
  • Active Comparator: Cediranib & Gefitinib
    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.
    Interventions:
    • Drug: cediranib maleate
    • Drug: gefitinib
  • Placebo Comparator: Cediranbib & placebo
    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.
    Interventions:
    • Drug: cediranib maleate
    • Drug: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
39
January 2014
May 2013   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 120 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
 
NCT01310855
CDR0000696313
UCL-10/0035
ZENECA-ISSRECE00002
EUDRACT-2010-021531-13
CRUKE/10/044
Yes
Not Provided
Not Provided
Not Provided
University College, London
University College, London
AstraZeneca
Principal Investigator: Paul Mulholland, PhD, MRCP, MSC, MBBS University College London Hospitals
University College, London
December 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP