Clinical trial NCT01310855: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Glioblastoma
Keywords: adult giant cell glioblastoma
adult glioblastoma
adult gliosarcoma
recurrent adult brain tumor
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2011-03-09
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression-free Survival
timeFrame: 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:
measure: Overall Survival
timeFrame: from date of randomization to date of Death due to any cause.
measure: Radiographic Response Rate
timeFrame: from baseline scan to six week and 12 week scans
measure: Progression-free Survival Rate at 6 Months
timeFrame: from the date of randomisation to 6 months
measure: Steroid Use
timeFrame: from randomization to first increase in dexamethasone dose
measure: Time to Deterioration of Neurological Status
timeFrame: 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.
measure: Safety and Tolerability
timeFrame: from date of randomisation to death
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: University College Hospital
state: England
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
city: Hull
country: United Kingdom
facility: Castle Hill Hospital
city: London
country: United Kingdom
facility: Charing Cross Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: University College London Hospitals
name: Paul Mulholland, PhD, MRCP, MSC, MBBS
role: PRINCIPAL_INVESTIGATOR
References:
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.