Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Cilengitide in Treating Patients With Recurrent or Progressive Glioblastoma Multiforme

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 and over NCI UCLA-0408014-01 EMD-121974-009, MERCK-EMD-121974-009, NCT0093964

Objectives

Primary

1. Determine the 6-month progression-free survival rate in patients with recurrent or progressive glioblastoma multiforme treated with 1 of 2 doses of cilengitide.

Secondary

1. Determine the objective response rate and duration in patients treated with this drug.
2. Determine the survival time of patients treated with this drug.
3. Determine the 1-year survival rate in patients treated with this drug.
4. Determine the time to disease progression in patients treated with this drug.
5. Determine the safety and tolerability of this drug in these patients.
6. Determine the pharmacokinetics of this drug in these patients.
7. Determine the quality of life of patients treated with this drug.

Entry Criteria

Disease Characteristics:

• Histologically confirmed glioblastoma multiforme (GBM)



• Recurrent or progressive disease after surgery or biopsy, external beam radiotherapy, AND 1 systemic chemotherapy* regimen
  • Recurrent disease in the contralateral hemisphere only must be histologically confirmed by biopsy
    • Bilateral recurrent disease (i.e., ipsilateral or contralateral disease) does not require histological confirmation by biopsy

   [Note: *Polifeprosan 20 with carmustine implant (Gliadel® wafer) is not considered systemic chemotherapy]




• Initial diagnosis with other conditions similar to GBM (e.g., anaplastic astrocytoma or low-grade glioma) that subsequently progressed to histologically confirmed GBM allowed



• Measurable disease
  • Solid contrast-enhancing lesion ≥ 1 cm in any dimension by gadolinium MRI within 2 weeks before initiation of study treatment



• Tumor tissue specimen available

Prior/Concurrent Therapy:

Biologic therapy

• At least 4 weeks since prior biologic therapy
• No prior antiangiogenic therapy

Chemotherapy

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
• No prior Gliadel® wafer placement during surgery for recurrent disease
• No concurrent chemotherapy

Endocrine therapy

• Concurrent corticosteroids allowed provided dose is stable for ≥ 5 days before initiation of study treatment

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy
• No prior radiotherapy dose > 66 Gray
• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• See Chemotherapy
• Recovered from prior surgery
• At least 2 weeks since prior surgery
• At least 1 week since prior biopsy
• No concurrent elective surgery
• No concurrent dental extraction or invasive dental procedures

Other

• More than 30 days since prior investigational agents
• At least 1 week since prior and no concurrent full anticoagulation with vitamin K antagonists leading to detectable changes in INR
• At least 1 week since prior and no concurrent IV heparin that results in prolonged PTT
  • Concurrent low molecular weight heparin allowed
• Concurrent anticonvulsants allowed provided dose is stable for ≥ 1 week before initiation of study treatment
• No other concurrent investigational agents

Patient Characteristics:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hematocrit ≥ 30%
• Hemoglobin ≥ 10 g/dL
• No history of coagulation disorder associated with bleeding

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• PT and PTT normal

Renal

• Creatinine ≤ 1.5 mg/dL

  OR

• Creatinine clearance ≥ 60 mL/min

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for ≥ 6 months after study participation
• Able to undergo MRI with gadolinium
• No peptic ulcer disease (i.e., endoscopically proven gastric ulcer, duodenal ulcer, or esophageal ulcer) within the past 6 months
• No other malignancy within the past 5 years except curatively treated basal cell skin cancer or carcinoma in situ of the cervix
• No severe infection
• No other significant illness that would preclude study participation
• No known hypersensitivity to study drug
• No known alcohol dependence or drug abuse

Expected Enrollment

A total of 80 patients (40 per treatment arm) will be accrued for this study within 8 months.

Outcomes

6-month progression-free survival rate

Objective response rate
Survival time
1-year survival rate
Time to disease progression
Safety and tolerability
Pharmacokinetics
Quality of life

Outline

This is an open-label, randomized, uncontrolled, multicenter study. Patients are stratified according to prior surgery at disease recurrence (yes vs no) and Karnofsky performance status (70-80% vs 90-100%). Patients are randomized to 1 of 2 doses of cilengitide.

Patients receive cilengitide IV over 1 hour on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, at the beginning of every other course during study treatment, and at the completion of study treatment.

After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter.

Trial Contact Information

Trial Lead Organizations

Jonsson Comprehensive Cancer Center at UCLA

Timothy Cloughesy, MD, Protocol chair		Ph: 310-825-5321; 888-798-0719 Email: tcloughesy@mednet.ucla.edu

Registry Information
Official Title		A Multicenter, Open-Label, Randomized, Uncontrolled, Phase IIa Trial in Subjects With Recurrent Glioblastoma Multiforme to Investigate the Clinical Activity, Safety, and Tolerability of EMD 121974 Administered as a Single Agent in Doses of 500mg or 2000 mg
Registered in ClinicalTrials.gov		NCT0093964
Date Submitted to PDQ		2004-12-15
Information Last Verified		2006-03-03
NCI Grant/Contract Number		CA16042