Cediranib Maleate With or Without Gefitinib in Treating Patients With Recurrent or Progressive Glioblastoma
Condition: Glioblastoma
MeSH terms: Glioblastoma
Intervention: cediranib maleate; gefitinib; Placebo
Intervention MeSH terms: Gefitinib; Cediranib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: adult giant cell glioblastoma; adult glioblastoma; adult gliosarcoma; recurrent adult brain tumor

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.
    

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