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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: May 2, 2017
Last verified: May 2017
  Purpose

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.


Condition Intervention Phase
Glioblastoma Drug: cediranib maleate Drug: gefitinib Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 38
Study Start Date: May 2011
Study Completion Date: January 2014
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
Drug: cediranib maleate Drug: Placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01310855

Locations
United Kingdom
University College Hospital
London, England, United Kingdom, NW1 2BU
Queen Elizabeth Hospital
Birmingham, United Kingdom
Bristol Haematology and Oncology Centre
Bristol, United Kingdom
Addenbrooke's Hospital
Cambridge, United Kingdom
Royal Surrey County Hospital
Guildford, United Kingdom
Castle Hill Hospital
Hull, United Kingdom
Charing Cross Hospital
London, United Kingdom
The Christie NHS Foundation Trust
Manchester, United Kingdom
Southampton General Hospital
Southampton, United Kingdom
Royal Marsden Hospital
Sutton, United Kingdom
Sponsors and Collaborators
University College, London
AstraZeneca
Investigators
Principal Investigator: Paul Mulholland, PhD, MRCP, MSC, MBBS University College London Hospitals
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01310855     History of Changes
Other Study ID Numbers: CDR0000696313
UCL-10/0035
ZENECA-ISSRECE00002
EUDRACT-2010-021531-13
CRUKE/10/044
Study First Received: March 5, 2011
Results First Received: December 2, 2016
Last Updated: May 2, 2017

Keywords provided by University College, London:
adult giant cell glioblastoma
adult glioblastoma
adult gliosarcoma
recurrent adult brain tumor

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Gefitinib
Cediranib
Maleic acid
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2017