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

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.

Study Overview

• Status: Terminated
• Conditions: Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Tumor
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Drug: cilengitide; Procedure: therapeutic conventional surgery

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
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Watertown, Massachusetts, United States, 02472
      • North American Brain Tumor Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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

Number of Arms

2

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6m-Progression-free Survival	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	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	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	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	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	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	24 hour post dose concentration plasma, at time of resection	24 hour post concentration
Tumor Tissue Concentrations	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	Kaplan-meier curve	1 year

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Mark Gilbert, North American Brain Tumor Consortium

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (ACTUAL): December 1, 2008
• Study Completion (ACTUAL): March 1, 2009

Study Registration Dates

• First Submitted: June 2, 2005
• First Submitted That Met QC Criteria: June 2, 2005
• First Posted (ESTIMATE): June 3, 2005

Study Record Updates

• Last Update Posted (ACTUAL): June 14, 2017
• Last Update Submitted That Met QC Criteria: May 16, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence; Gliosarcoma
• 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)?: NO