Cilengitide in Treating Younger Patients With Recurrent or Progressive High-Grade Glioma That Has Not Responded to Standard Therapy

PRIMARY OBJECTIVES:

I. To determine the objective response rate to cilengitide in younger patients with recurrent
or progressive high-grade glioma that is refractory to standard therapy.

SECONDARY OBJECTIVES:

I. To estimate the distribution of time to progression, time to treatment failure, and time
to death in these patients.

II. To estimate the rate of toxicity, especially symptomatic intratumoral hemorrhage, in
these patients.

III. To evaluate the pharmacokinetics of cilengitide in plasma using a limited sampling
strategy.

IV. To evaluate the pharmacogenetic polymorphisms in drug transporters (eg, breast cancer
resistance protein [BCRP], P-glycoprotein [P-gp]) and relate to cilengitide disposition.

OUTLINE:

Patients receive cilengitide IV over 1 hour on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and
then periodically for 3 years.

Inclusion Criteria:

- Histologically confirmed primary central nervous system (CNS) high-grade glioma,
including any of the following:

- Glioblastoma multiforme

- Anaplastic astrocytoma

- Anaplastic oligodendroglioma

- High-grade astrocytoma not otherwise specified (i.e., anaplastic ganglioglioma,
anaplastic mixed glioma, or anaplastic mixed glioneuronal tumors)

- No diffuse pontine gliomas, gliomatosis cerebri, and primary spinal cord
high-grade astrocytoma

- Gliosarcoma

- Recurrent or progressive disease that is refractory to standard therapy

- Radiographically documented measurable disease

- Lesion must be at least twice the thickness of the image from which it is derived
(e.g., 10 mm for a 5 mm slice thickness)

- No diffuse pontine gliomas

- No evidence of prior CNS bleeding

- Karnofsky performance status (PS) 50-100% (patients > 16 years of age)

- Lansky PS 50-100% (patients =< 16 years of age)

- Life expectancy >= 8 weeks

- Absolute neutrophil count (ANC) >= 1,000/μL

- Platelet count >= 100,000/μL (transfusion independent)

- Hemoglobin >= 8.0 g/dL (red blood cell [RBC] transfusions allowed)

- Creatinine clearance or radioisotope glomerular filtration rate >= 70mL/min OR serum
creatinine based on age/gender as follows:

- 0.4 mg/dL (1 month to < 6 months of age)

- 0.5 mg/dL (6 months to < 1 year of age)

- 0.6 mg/dL (1 to < 2 years of age)

- 0.8 mg/dL (2 to < 6 years of age)

- 1.0 mg/dL (6 to < 10 years of age)

- 1.2 mg/dL (10 to < 13 years of age)

- 1.5 mg/dL (male) or 1.4mg/dL (female) (13 to < 16 years of age)

- 1.7 mg/dL (male) or 1.4mg/dL (female) (>= 16 years of age)

- Total bilirubin =< 1.5 times upper limit of normal (ULN) for age

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 times ULN
for age

- No evidence of dyspnea at rest

- No exercise intolerance

- Pulse oximetry > 94%, if determination is clinically indicated

- Seizure disorder is allowed provided it is well-controlled with anticonvulsants

- No uncontrolled infection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Recovered from all prior therapy

- No more than two prior treatments for high-grade glioma (i.e., one initial treatment
and one treatment for relapse)

- More than 2 weeks since prior myelosuppressive chemotherapy (>= 6 weeks for
nitrosoureas)

- At least 1 week since prior non-myelosuppressive chemotherapy, immunotherapy, or
biologic therapy

- At least 2 weeks since prior local palliative radiotherapy (i.e., small port) to a
symptomatic non-target lesion only

- At least 3 months since prior craniospinal radiotherapy

- At least 6 weeks since prior substantial bone marrow radiotherapy

- At least 6 months since prior allogeneic stem cell transplant (SCT) or rescue

- Patients who have undergone prior allogeneic SCT and who have graft-versus-host
disease (GVHD) must have controlled GVHD that is =< grade 2

- At least 1 month since prior autologous SCT

- More than 1 week since prior growth factors (> 3 weeks for pegfilgrastim [Neulasta®])

- No other concurrent anticancer therapy, including chemotherapy or immunomodulating
agents

- No other concurrent experimental agents or therapies

- No concurrent alternative or complimentary therapies

- No concurrent homeopathic medicines

- No concurrent nonsteroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid
(aspirin)

- No concurrent steroids as anti-emetics

- Concurrent steroids for treatment of increased intracranial pressure allowed if on a
stable or decreasing dose for >= 1 week before study entry

- Concurrent radiotherapy to localized painful lesions allowed provided >= 1 measurable
lesion is not irradiated