Phase II Trial of EMD 121974 for Recurrent Glioblastoma: A Clinical Trial With Tissue Correlates of Response
Phase II Trial of EMD 121974 for Recurrent Glioblastoma: A Clinical Trial With Tissue Correlates of Response
Cilengitide may stop the growth of glioblastoma multiforme by blocking blood flow to the tumor. Giving cilengitide before and after surgery may be an effective treatment for glioblastoma multiforme. This phase II trial is studying how well cilengitide works in treating patients who are undergoing surgery for recurrent or progressive glioblastoma multiforme.
PRIMARY OBJECTIVES:
I. Determine the 6-month progression-free survival rate in operative patients with recurrent or progressive glioblastoma multiforme treated with cilengitide.
SECONDARY OBJECTIVES:
I. Determine the safety and toxicity of this drug in these patients.
OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment groups for the preoperative treatment component.
Preoperative Treatment Group I: Patients receive high-dose cilengitide IV over 1 hour on days -8, -4, and -1.
Preoperative Treatment Group II: Patients receive low-dose cilengitide IV over 1 hour on days -8, -4, and -1.
Resection: All patients undergo tumor resection on day 0.
Postoperative Treatment: Beginning within 2 weeks after surgery, all patients receive high-dose cilengitide IV over 1 hour twice weekly for 4 weeks. Treatment repeats every 4 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 44 patients (22 per preoperative treatment group) will be accrued for this study.
Inclusion Criteria:
Histologically confirmed intracranial glioblastoma multiforme (GBM)
Original diagnosis of low-grade glioma with subsequent histological confirmation of GBM allowed
Recurrent disease
Must require a surgical procedure (gross total or near gross total resection) for tumor removal
Performance status - Karnofsky 60-100%
White Blood Count (WBC) ≥ 3,000/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 10 g/dL (transfusion allowed)
Serum glutamic oxaloacetic transaminase (SGOT) < 2 times upper limit of normal (ULN)
Bilirubin < 2 times ULN
Creatinine < 1.5 mg/dL
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective barrier contraception during and for ≥ 2 weeks after study participation (for female patients) or for 3 months after study participation (for male patients)
No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
No active infection
No other significant uncontrolled medical illness that would preclude study participation
At least 3 weeks since prior interferon
No prior cilengitide
No other prior targeted antiangiogenic treatment (e.g., vatalanib, SU5416, or thalidomide)
No concurrent anticancer immunotherapy
No concurrent routine prophylactic filgrastim (G-CSF)
At least 2 weeks since prior vincristine
At least 3 weeks since prior procarbazine
At least 6 weeks since prior nitrosoureas
No concurrent anticancer chemotherapy
At least 3 weeks since prior tamoxifen
No concurrent anticancer hormonal therapy
See Disease Characteristics
At least 4 weeks since prior radiotherapy
No concurrent anticancer radiotherapy
Recovered from all prior therapies
No more than 3 prior treatments for GBM (1 initial treatment; and treatment for 2 relapses)
At least 4 weeks since prior investigational agents
At least 4 weeks since prior cytotoxic therapy
At least 3 weeks since other prior non-cytotoxic therapy (e.g., isotretinoin), except radiosensitizers
No other concurrent anticancer therapy
No other concurrent investigational agents