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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT01310855
First received: March 5, 2011
Last updated: November 26, 2012
Last verified: November 2012
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: from date of randomization to date of Death due to any cause. ] [ Designated as safety issue: No ]
  • Radiographic response rate [ Time Frame: from baseline scan to six week and 12 week scans ] [ Designated as safety issue: No ]
  • Progression-free survival rate at 6 months [ Time Frame: from the date of randomisation to 6 months ] [ Designated as safety issue: No ]
  • Steroid use [ Time Frame: from randomization to first increase in dexamethasone dose ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • Safety and tolerability [ Time Frame: from date of randomisation to death ] [ Designated as safety issue: Yes ]

Enrollment: 39
Study Start Date: May 2011
Estimated Study Completion Date: November 2013
Estimated Primary Completion Date: November 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 and older
Genders Eligible for Study:   Both
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
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

No publications provided

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
Last Updated: November 26, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

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
Maleic acid
Gefitinib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on April 22, 2014