An Open Label, Phase 2 Study Evaluating the Safety and Efficacy of IMC-3G3 or IMC-1121B in Patients With Recurrent Glioblastoma Multiforme

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed supratentorial glioblastoma multiforme (GBM)

- Patients with prior low-grade glioma who progressed after radiotherapy ±
chemotherapy and are biopsied and found to have GBM are eligible

- Progressive or recurrent disease after radiotherapy ± chemotherapy

- Measurable disease by contrast-enhanced MRI or CT scan

PATIENT CHARACTERISTICS:

- Karnofsky performance status 60-100%

- Life expectancy ≥ 3 months

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 9 g/dL

- Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 60 mL/min

- Total bilirubin ≤ 1.5 mg/dL

- Transaminases ≤ 3 times upper limit of normal (ULN)

- Urine protein ≤ 2+ by dipstick or urinalysis or ≤ 1,000 mg by 24-hour urine
collection

- INR ≤ 1.5

- PTT ≤ 5 seconds above ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 12 weeks after
completion of study treatment

- Mini Mental State Exam score ≥ 15

- Able to undergo MRI (i.e., no pacemaker, aneurysm clip, or claustrophobia)

- No concurrent serious infection or medical illness that would jeopardize the ability
of the patient to receive the treatment outlined in this study with reasonable safety
including, but not limited to, any of the following:

- Uncontrolled hypertension

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness/social situation that would limit compliance with study
requirements

- No other malignancy within the past 5 years, except curatively treated carcinoma in
situ or basal cell carcinoma of the skin

- No major bleeding episode within the past 3 months

- No myocardial infarction, unstable angina pectoris, cerebrovascular accident, or
transient ischemic attack within the past 6 months

- No serious or non-healing wound, ulcer, or bone fracture

- No uncontrolled or poorly controlled hypertension, despite standard medical
management

- No known allergy to any of the treatment components

- No known HIV positivity or AIDS-related illness

- No uncontrolled thrombotic or hemorrhagic disorders

- No grade 3-4 gastrointestinal bleeding within the past 3 months

- No gross hemoptysis (≥ ½ teaspoon) within the past 2 months

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Recovered from prior therapy

- At least 3 months since prior radiotherapy

- At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)

- At least 2 weeks since prior FDA-approved, non-cytotoxic agents (e.g., celecoxib,
thalidomide)

- At least 3 weeks since prior investigational, non-cytotoxic agents

- More than 28 days since prior major surgery, including brain biopsy

- More than 7 days since prior subcutaneous venous access device placement

- No prior treatment with other agents that directly inhibit PDGFRα/β, PDGF, VEGF, or
VEGFRs

- No concurrent therapeutic anticoagulation, chronic daily treatment with aspirin (>
325 mg/day), or other known inhibitors of platelet function

- No concurrent prophylactic hematopoietic growth factors (e.g., erythropoietin, G-CSF,
GM-CSF, or IL-11) during the first course of treatment

- No concurrent elective or planned surgery

- No other concurrent therapy for the tumor (e.g., chemotherapy or investigational
agents)

- Concurrent steroids allowed