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

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ClinicalTrials.gov Identifier: NCT00112866
Recruitment Status : Terminated (due to poor accrual)
First Posted : June 3, 2005
Results First Posted : June 14, 2017
Last Update Posted : June 14, 2017
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Recurrent Adult Brain Tumor Drug: cilengitide Procedure: therapeutic conventional surgery Other: pharmacological study Other: laboratory biomarker analysis Phase 2

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 : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of EMD 121974 for Recurrent Glioblastoma: A Clinical Trial With Tissue Correlates of Response
Study Start Date : January 2005
Actual Primary Completion Date : December 2008
Actual Study Completion Date : March 2009


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.

Drug: cilengitide
Given IV
Other Name: EMD 121974
Procedure: therapeutic conventional surgery
Undergo tumor resection
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
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

Drug: cilengitide
Given IV
Other Name: EMD 121974
Procedure: therapeutic conventional surgery
Undergo tumor resection
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies



Primary Outcome Measures :
  1. 6m-Progression-free Survival [ Time Frame: 6 months ]
    progression within 6 months (26 weeks) of treatment


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Plasma Concentration of EMD 121974 [ Time Frame: 24 hour post concentration ]
    24 hour post dose concentration plasma, at time of resection

  7. 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.


Other Outcome Measures:
  1. Overall Progression Free Survival [ Time Frame: 1 year ]
    Kaplan-meier curve



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00112866


Locations
United States, Massachusetts
North American Brain Tumor Consortium
Watertown, Massachusetts, United States, 02472
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Mark Gilbert North American Brain Tumor Consortium

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00112866     History of Changes
Other Study ID Numbers: NCI-2012-02653
NCI-2012-02653 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000428409
NABTC-03-02 ( Other Identifier: North American Brain Tumor Consortium )
NABTC-03-02 ( Other Identifier: CTEP )
U01CA062399 ( U.S. NIH Grant/Contract )
First Posted: June 3, 2005    Key Record Dates
Results First Posted: June 14, 2017
Last Update Posted: June 14, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Glioblastoma
Gliosarcoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue