RATIONALE: Cilengitide may stop the growth of cancer by stopping blood flow to the tumor. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining cilengitide with radiation therapy may kill more tumor cells.

PURPOSE: Randomized phase I/II trial to study the effectiveness of combining cilengitide with radiation therapy in treating patients who have newly diagnosed glioblastoma multiforme.

Condition	Treatment or Intervention	Phase
adult glioblastoma adult giant cell glioblastoma adult gliosarcoma	Drug: cilengitide  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: growth factor antagonist therapy  Procedure: radiation therapy	Phase I Phase II

OBJECTIVES:

• Determine the safety profile of cilengitide and radiotherapy in patients with newly diagnosed glioblastoma multiforme.

Primary

• Determine the overall survival of patients treated with this regimen.

Secondary

• Compare overall survival of patients treated with radiotherapy and low-dose cilengitide vs high-dose cilengitide.
• Determine the toxicity of radiotherapy and cilengitide in these patients.
• Correlate molecular expression profile with clinical outcomes of patients treated with this regimen.
• Determine tumor blood volume, tumor blood flow, and permeability ratios using perfusion MR in patients treated with this regimen.

OUTLINE: This is an open-label, multicenter, phase I dose-escalation study of cilengitide followed by a randomized phase II study.

• Initiation course: Patients receive cilengitide IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also undergo radiotherapy once daily on days 1-5 of weeks 1-6.
• Maintenance courses: Patients receive cilengitide IV 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. Cohorts of 3-6 patients receive escalating doses of cilengitide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity.
• Patients are stratified according to age (50 and under vs over 50), Karnofsky performance score (60%-80% vs 90%-100%), and tumor status (measurable vs nonmeasurable). Patients are randomized to 1 of 2 treatment arms.
• Arm I: Patients receive radiotherapy as in phase I initiation course and cilengitide at a lower dose as in phase I initiation and maintenance courses.
• Arm II: Patients receive radiotherapy as in phase I initiation course and cilengitide at a higher dose as in phase I initiation and maintenance courses. Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 9-112 patients (9-18 for phase I and 94 [47 per treatment arm] for phase II) will be accrued for this study within 1.5-37 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed glioblastoma multiforme
• Supratentorial grade IV astrocytoma

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Transaminases ≤ 4 times upper limit of normal
• Bilirubin ≤ 1.5 mg/dL

Renal

• Creatinine ≤ 1.5 mg/dL OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No advanced coronary disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 8 weeks after study participation
• Mini Mental State Exam score ≥ 15
• Able to undergo MRI evaluation
• No history of wound-healing disorders
• No peptic ulcer disease within the past year
• No concurrent serious infection or medical illness that would preclude study participation
• No other malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior immunotherapy for brain tumor
• No prior biologic agents for brain tumor, including any of the following:
• Immunotoxins
• Immunoconjugates
• Antisense agents
• Peptide receptor antagonists
• Interferons
• Interleukins
• Tumor-infiltrating lymphocytes
• Lymphokine-activated killer cells
• Gene therapy
• No concurrent prophylactic filgrastim (G-CSF)

Chemotherapy

• No prior chemotherapy for brain tumor
• No concurrent chemotherapy for brain tumor

Endocrine therapy

• No prior hormonal therapy for brain tumor
• Patients must be maintained on a corticosteroid regimen that has been stable for the past 5 days
• Prior glucocorticoid therapy allowed

Radiotherapy

• No prior radiotherapy for brain tumor
• No concurrent intensity modulated radiotherapy

Surgery

• Recovered from prior immediate post-operative period
• At least 1 week since prior craniotomy

Other

• No other concurrent investigational agents for brain tumor

Study chairs or principal investigators

Louis Burt Nabors, MD,  Study Chair,  UAB Comprehensive Cancer Center   

Study ID Numbers:  CDR0000368451; NABTT-0306
Record last reviewed:  May 2004
Record first received:  June 10, 2004
ClinicalTrials.gov Identifier:  NCT00085254
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-20