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

Glioblastoma Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01310855
• Other study ID #: CDR0000696313
• Secondary ID: UCL-10/0035ZENEC
• Status: Terminated
• Phase: Phase 2
• First received: March 5, 2011
• Last updated: July 3, 2014
• Start date: May 2011
• Est. completion date: January 2014

Study information

• Verified date: July 2014
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 39
• Est. completion date: January 2014
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Drug:
• cediranib maleate

• gefitinib

• Placebo

Locations

Country	Name	City	State
United Kingdom	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	University College Hospital	London	England
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Southampton General Hospital	Southampton
United Kingdom	Royal Marsden Hospital	Sutton

Sponsors (2)

Lead Sponsor	Collaborator
University College, London	AstraZeneca

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival		from the date of randomisation to the date of first progression or death due to any cause	No
Secondary	Overall survival		from date of randomization to date of Death due to any cause.	No
Secondary	Radiographic response rate		from baseline scan to six week and 12 week scans	No
Secondary	Progression-free survival rate at 6 months		from the date of randomisation to 6 months	No
Secondary	Steroid use		from randomization to first increase in dexamethasone dose	No
Secondary	Time to deterioration of neurological status		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.	No
Secondary	Safety and tolerability		from date of randomisation to death	Yes