Cilengitide in Treating Patients Who Are Undergoing Surgery for Recurrent or Progressive Glioblastoma Multiforme
Phase II Trial of EMD 121974 for Recurrent Glioblastoma: A Clinical Trial With Tissue Correlates of Response
Study Overview
Status
Conditions
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 Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Massachusetts
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Watertown, Massachusetts, United States, 02472
- North American Brain Tumor Consortium
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
EXPERIMENTAL: Group I (high-dose cilengitide) 2000mg
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. |
Correlative studies
Correlative studies
Other Names:
Given IV
Other Names:
Undergo tumor resection
|
|
EXPERIMENTAL: Group II (low-dose cilengitide) 500mg
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 |
Correlative studies
Correlative studies
Other Names:
Given IV
Other Names:
Undergo tumor resection
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
6m-Progression-free Survival
Time Frame: 6 months
|
progression within 6 months (26 weeks) of treatment
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Changes in avb3 Integrin Expression on Tumor Cells and Endothelial Cells
Time Frame: 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.
|
Baseline and time of surgery
|
|
Changes in Vitronectin Expression
Time Frame: 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.
|
Baseline and time of surgery
|
|
Changes in Tumor Cell Apoptosis
Time Frame: 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.
|
Baseline and time of surgery
|
|
Changes in Tumor Cell Proliferation
Time Frame: 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.
|
Baseline and time of surgery
|
|
Changes in Endothelial Cell Apoptosis
Time Frame: 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.
|
Baseline and up to 4 years
|
|
Plasma Concentration of EMD 121974
Time Frame: 24 hour post concentration
|
24 hour post dose concentration plasma, at time of resection
|
24 hour post concentration
|
|
Tumor Tissue Concentrations
Time Frame: 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.
|
at time of surgery
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Overall Progression Free Survival
Time Frame: 1 year
|
Kaplan-meier curve
|
1 year
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Mark Gilbert, North American Brain Tumor Consortium
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NCI-2012-02653 (REGISTRY: CTRP (Clinical Trial Reporting Program))
- U01CA062399 (U.S. NIH Grant/Contract)
- CDR0000428409
- NABTC-03-02 (OTHER: CTEP)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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