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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)

Tracking Information
First Submitted Date  ICMJE June 2, 2005
First Posted Date  ICMJE June 3, 2005
Results First Submitted Date  ICMJE October 7, 2016
Results First Posted Date  ICMJE June 14, 2017
Last Update Posted Date June 14, 2017
Study Start Date  ICMJE January 2005
Actual Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 16, 2017)
6m-Progression-free Survival [ Time Frame: 6 months ]
progression within 6 months (26 weeks) of treatment
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2017)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Plasma Concentration of EMD 121974 [ Time Frame: 24 hour post concentration ]
    24 hour post dose concentration plasma, at time of resection
  • 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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: May 16, 2017)
Overall Progression Free Survival [ Time Frame: 1 year ]
Kaplan-meier curve
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cilengitide in Treating Patients Who Are Undergoing Surgery for Recurrent or Progressive Glioblastoma Multiforme
Official Title  ICMJE Phase II Trial of EMD 121974 for Recurrent Glioblastoma: A Clinical Trial With Tissue Correlates of Response
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Recurrent Adult Brain Tumor
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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.

    Interventions:
    • Drug: cilengitide
    • Procedure: therapeutic conventional surgery
    • Other: pharmacological study
    • Other: laboratory biomarker analysis
  • 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

    Interventions:
    • Drug: cilengitide
    • Procedure: therapeutic conventional surgery
    • Other: pharmacological study
    • Other: laboratory biomarker analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: May 16, 2017)
30
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE March 2009
Actual Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00112866
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mark Gilbert North American Brain Tumor Consortium
PRS Account National Cancer Institute (NCI)
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP