Clinical trial NCT00112866: Cilengitide in Treating Patients Who Are Undergoing Surgery for Recurrent or Progressive Glioblastoma Multiforme
Official title: Phase II Trial of EMD 121974 for Recurrent Glioblastoma: A Clinical Trial With Tissue Correlates of Response
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2005-06-03
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: 6m-Progression-free Survival
timeFrame: 6 months
Secondary outcomes:
measure: Changes in avb3 Integrin Expression on Tumor Cells and Endothelial Cells
timeFrame: Baseline and time of surgery
measure: Changes in Vitronectin Expression
timeFrame: Baseline and time of surgery
measure: Changes in Tumor Cell Apoptosis
timeFrame: Baseline and time of surgery
measure: Changes in Tumor Cell Proliferation
timeFrame: Baseline and time of surgery
measure: Changes in Endothelial Cell Apoptosis
timeFrame: Baseline and up to 4 years
measure: Plasma Concentration of EMD 121974
timeFrame: 24 hour post concentration
measure: Tumor Tissue Concentrations
timeFrame: at time of surgery
Other outcomes:
measure: Overall Progression Free Survival
timeFrame: 1 year
Locations:
city: Watertown
country: United States
facility: North American Brain Tumor Consortium
state: Massachusetts
Study officials:
affiliation: North American Brain Tumor Consortium
name: Mark Gilbert
role: PRINCIPAL_INVESTIGATOR
References: