Cilengitide in Treating Patients Who Are Undergoing Surgery for Recurrent or Progressive Glioblastoma Multiforme

National Cancer Institute (NCI)

Status and phase: Terminated; Phase 2

Conditions: Recurrent Adult Brain Tumor; Adult Glioblastoma; Adult Giant Cell Glioblastoma; Adult Gliosarcoma

Treatments: Other: laboratory biomarker analysis; Drug: cilengitide; Procedure: therapeutic conventional surgery; Other: pharmacological study

Study type: Interventional

Funder types: NIH

Identifiers

NCT00112866

NCI-2012-02653 (Registry Identifier)

U01CA062399 (U.S. NIH Grant/Contract)

NABTC-03-02 (Other Identifier)

CDR0000428409

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 30 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Histologically confirmed intracranial glioblastoma multiforme (GBM)

  • Original diagnosis of low-grade glioma with subsequent histological confirmation of GBM allowed

  • Recurrent disease

    • Failed prior radiotherapy

• 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)

  • For patients who received prior therapy for low-grade glioma, a subsequent surgical diagnosis of high-grade glioma is considered the first relapse

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 2 patient groups

Group I (high-dose cilengitide) 2000mg

Experimental group

Description:

Preoperative Treatment: Patients receive high-dose cilengitide IV over 1 hour on days -8, -4, and -1. (High dose 2000mg) 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.

Treatment:

Procedure: therapeutic conventional surgery

Other: laboratory biomarker analysis

Other: pharmacological study

Drug: cilengitide

Group II (low-dose cilengitide) 500mg

Experimental group

Description:

Preoperative Treatment: Patients receive low-dose cilengitide IV over 1 hour on days -8, -4, and -1. (500mg) 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

Treatment:

Procedure: therapeutic conventional surgery

Other: laboratory biomarker analysis

Other: pharmacological study

Drug: cilengitide