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

Phase 2

Terminated

• Conditions: Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Tumor
• Interventions: Drug: cilengitide; Procedure: therapeutic conventional surgery; Other: pharmacological study; Other: laboratory biomarker analysis

• Registration Number: NCT00112866
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 2005-01
• Study First Submitted: 2005-06-02
• Study First Submitted QC: 2005-06-02
• Study First Posted: 2005-06-03
• Primary Completion: 2008-12
• Study Completion: 2009-03
• Results First Submitted: 2016-10-07
• Status Verified: 2017-05
• Results First Submitted QC: 2017-05-16
• Last Update Submitted: 2017-05-16
• Results First Posted: 2017-06-14
• Last Update Posted: 2017-06-14

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 30

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

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group II (low-dose cilengitide) 500mg	therapeutic conventional surgery	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
Group I (high-dose cilengitide) 2000mg	cilengitide	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.
Group I (high-dose cilengitide) 2000mg	therapeutic conventional surgery	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.
Group I (high-dose cilengitide) 2000mg	pharmacological study	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.
Group I (high-dose cilengitide) 2000mg	laboratory biomarker analysis	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.
Group II (low-dose cilengitide) 500mg	cilengitide	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
Group II (low-dose cilengitide) 500mg	pharmacological study	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
Group II (low-dose cilengitide) 500mg	laboratory biomarker analysis	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

Primary Outcome Measures

Name	Time	Method
6m-Progression-free Survival	6 months	progression within 6 months (26 weeks) of treatment

Secondary Outcome Measures

Name	Time	Method
Changes in avb3 Integrin Expression on Tumor Cells and Endothelial Cells	Baseline and time of surgery	Will be performed between the untreated matched control tumor tissue and the tissue obtained from the post-treatment tumors using either a Fisher's Exact test or the Wilcoxon rank sum test depending on whether the assay provides a measurement or is yes/no.
Changes in Vitronectin Expression	Baseline and time of surgery	Will be performed between the untreated matched control tumor tissue and the tissue obtained from the post-treatment tumors using either a Fisher's Exact test or the Wilcoxon rank sum test depending on whether the assay provides a measurement or is yes/no.
Changes in Tumor Cell Apoptosis	Baseline and time of surgery	Will be performed between the untreated matched control tumor tissue and the tissue obtained from the post-treatment tumors using either a Fisher's Exact test or the Wilcoxon rank sum test depending on whether the assay provides a measurement or is yes/no.
Changes in Endothelial Cell Apoptosis	Baseline and up to 4 years	Will be performed between the untreated matched control tumor tissue and the tissue obtained from the post-treatment tumors using either a Fisher's Exact test or the Wilcoxon rank sum test depending on whether the assay provides a measurement or is yes/no.
Tumor Tissue Concentrations	at time of surgery	a section of tumor of approximately 500mg will be snap frozen (immediately prepared and frozen) once removed from brain for analysis of the drug concentration in contrast -enhancing tumor.
Changes in Tumor Cell Proliferation	Baseline and time of surgery	Will be performed between the untreated matched control tumor tissue and the tissue obtained from the post-treatment tumors using either a Fisher's Exact test or the Wilcoxon rank sum test depending on whether the assay provides a measurement or is yes/no.
Plasma Concentration of EMD 121974	24 hour post concentration	24 hour post dose concentration plasma, at time of resection

Trial Locations

Locations (1)

North American Brain Tumor Consortium; 🇺🇸 Watertown, Massachusetts, United States