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

Adult Glioblastoma Clinical Trial

Official title:

Phase II Trial of EMD 121974 for Recurrent Glioblastoma: A Clinical Trial With Tissue Correlates of Response

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00112866
• Other study ID #: NCI-2012-02653
• Secondary ID: NCI-2012-02653CD
• Status: Completed
• Phase: Phase 2
• First received: June 2, 2005
• Last updated: October 25, 2013
• Start date: January 2005

Study information

• Verified date: October 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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%

• WBC = 3,000/mm^3

• Absolute neutrophil count = 1,500/mm^3

• Platelet count = 100,000/mm^3

• Hemoglobin = 10 g/dL (transfusion allowed)

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adult Giant Cell Glioblastoma
• Adult Glioblastoma
• Adult Gliosarcoma
• Glioblastoma
• Gliosarcoma
• Recurrent Adult Brain Tumor

Intervention

Drug:
• cilengitide
Given IV

Procedure:
• therapeutic conventional surgery
Undergo tumor resection

Other:
• pharmacological study
Correlative studies
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	North American Brain Tumor Consortium	Watertown	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival		6 months	No
Secondary	Changes in avb3 integrin expression on tumor cells and endothelial cells	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.	Baseline and up to 4 years	No
Secondary	Changes in vitronectin expression	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.	Baseline and up to 4 years	No
Secondary	Changes in tumor cell apoptosis	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.	Baseline and up to 4 years	No
Secondary	Changes in tumor cell proliferation	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.	Baseline and up to 4 years	No
Secondary	Changes in endothelial cell apoptosis	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.	Baseline and up to 4 years	No