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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00112866
First received: June 2, 2005
Last updated: October 25, 2013
Last verified: October 2013
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of EMD 121974 for Recurrent Glioblastoma: A Clinical Trial With Tissue Correlates of Response

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in avb3 integrin expression on tumor cells and endothelial cells [ Time Frame: Baseline and up to 4 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and up to 4 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and up to 4 years ] [ Designated as safety issue: No ]
    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 proliferation [ Time Frame: Baseline and up to 4 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and up to 4 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 44
Study Start Date: January 2005
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group I (high-dose cilengitide)

Preoperative Treatment: Patients receive high-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.

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)

Preoperative Treatment: 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

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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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%
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00112866

Locations
United States, Massachusetts
North American Brain Tumor Consortium
Watertown, Massachusetts, United States, 02472
Sponsors and Collaborators
Investigators
Principal Investigator: Mark Gilbert North American Brain Tumor Consortium
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00112866     History of Changes
Other Study ID Numbers: NCI-2012-02653, NCI-2012-02653, CDR0000428409, NABTC-03-02, NABTC-03-02, U01CA062399
Study First Received: June 2, 2005
Last Updated: October 25, 2013
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 24, 2014