Overview

This trial is active, not recruiting.

Conditions adult giant cell glioblastoma, adult glioblastoma, adult gliosarcoma
Treatments cilengitide, temozolomide, radiation therapy, laboratory biomarker analysis, pharmacological study
Phase phase 1/phase 2
Sponsor National Cancer Institute (NCI)
Start date April 2005
End date November 2012
Trial size 112 participants
Trial identifier NCT00085254, CDR0000368451, NABTT 0306, NCI-2012-02932, U01CA062475

Summary

Cilengitide may stop the growth of cancer by stopping blood flow to the tumor. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving cilengitide together with temozolomide and radiation therapy may kill more tumor cells. This randomized phase I/II trial is studying the side effects and best dose of cilengitide when given together with temozolomide and radiation therapy and to compare how well they work in treating patients with newly diagnosed glioblastoma multiforme

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
INITIATION COURSE: Patients receive cilengitide IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6. MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV 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. PHASE II: Patients receive radiotherapy and temozolomide as in phase I initiation course and cilengitide at a lower dose as in phase I initiation and maintenance courses.
cilengitide EMD 121974
Given IV
temozolomide SCH 52365
Given orally
radiation therapy irradiation
Undergo radiotherapy
laboratory biomarker analysis
Correlative studies
pharmacological study pharmacological studies
Correlative studies
(Experimental)
INITIATION COURSE: Patients receive cilengitide IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6. MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV 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. PHASE II: Patients receive radiotherapy and temozolomide as in phase I initiation course and cilengitide at a higher dose as in phase I initiation and maintenance courses.
cilengitide EMD 121974
Given IV
temozolomide SCH 52365
Given orally
radiation therapy irradiation
Undergo radiotherapy
laboratory biomarker analysis
Correlative studies
pharmacological study pharmacological studies
Correlative studies

Primary Outcomes

Measure
MTD defined as the dose level producing dose limiting toxicity (DLT) in 2 out of 6 patients assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)
time frame: 28 days
Overall failure rate (Phase II)
time frame: From time of histological diagnosis to death occurrence, assessed up to 1 year

Secondary Outcomes

Measure
Separate failure rates
time frame: Up to 1 year
Frequency of grade 3 or 4 toxicities assessed using CTCAE version 4.0
time frame: Up to 1 year
Change in tumor blood volume, tumor blood flow, and permeability
time frame: Baseline and up to 1 year

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Patients must have histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme) - Patients must not have received prior radiation therapy, chemotherapy, immunotherapy or therapy with biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, TIL, LAK or gene therapy), or hormonal therapy for their brain tumor; glucocorticoid therapy is allowed - Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others) - Absolute neutrophil count >= 1500/mm^3 - Platelets >= 100,000/mm^3 - Creatinine =< 1.5 mg/dl or creatinine clearance >= 60 mL/min - Total bilirubin =< 1.5 mg/dl - Transaminases =< 4 times above the upper limits of the institutional normal - Patients must be able to provide written informed consent - Patients must have recovered from the immediate post-operative period and be maintained on a stable corticosteroid regimen (no increase for 5 days) prior to the start of treatment - Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception; women of childbearing potential must have a negative pregnancy test - Patients must have a Mini Mental State Exam score of >= 15 - Patients must have tumor tissue form completed and signed by a pathologist Exclusion Criteria: - Patients with serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety - Patients who are pregnant or breast-feeding - Patients receiving concurrent therapy for their tumor (i.e. chemotherapeutics or investigational agents) - Patients with a concurrent or prior malignancy are ineligible unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin; patients who have been free of disease (any prior malignancy) for >= five years are eligible for this study - Patients who are unable to undergo an MRI evaluation - Patients with a history of wound-healing disorders, advanced coronary disease, or with a recent history (# 1 year) of peptic ulcer disease are ineligible

Additional Information

Official title A Safety Run-in/Randomized Phase II Trial of EMD 121974 in Conjunction With Concomitant and Adjuvant Temozolomide With Radiation Therapy in Patients With Newly Diagnosed Glioblastoma Multiforme
Principal investigator Louis Nabors
Description PRIMARY OBJECTIVES: I. To assess the safety profile of EMD 121974 (cilengitide) when administered as a one-hour infusion twice a week concurrently with concomitant and adjuvant temozolomide with radiation therapy for newly diagnosed glioblastoma multiforme. (Phase I) II. To estimate overall survival in newly diagnosed patients with glioblastoma multiforme treated with EMD 121974 concurrently with concomitant and adjuvant temozolomide with radiation therapy. (Phase II) SECONDARY OBJECTIVES: I. To estimate and compare overall survival between a low dose treatment group and a high dose treatment group in newly diagnosed patients with glioblastoma multiforme treated with EMD 121974 concurrently with concomitant and adjuvant temozolomide with radiation therapy. (Phase II) II. To determine the toxicity of EMD 121974 (cilengitide) when it is administered in conjunction with concomitant and adjuvant temozolomide with radiation therapy in patients with newly diagnosed glioblastoma multiforme. (Phase II) III. To evaluate the molecular profile of individual patients and correlate molecular expression profiles with clinical outcomes. (Phase II) IV. To characterize tumor blood volume, tumor blood flow, and permeability ratios using perfusion MR in newly diagnosed glioblastoma multiforme and follow these parameters during treatment with EMD 121974 (cilengitide). (Phase II) OUTLINE: This is an open-label, multicenter, phase I dose-escalation study of cilengitide followed by a randomized phase II study. PHASE I: INITIATION COURSE: Patients receive cilengitide IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6. MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV 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. Cohorts of 3-6 patients receive escalating doses of cilengitide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity. PHASE II: Patients are stratified according to age (50 and under vs over 50), Karnofsky performance score (60%-80% vs 90%-100%), and tumor status (measurable vs nonmeasurable). Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive radiotherapy and temozolomide as in phase I initiation course and cilengitide at a lower dose as in phase I initiation and maintenance courses. ARM II: Patients receive radiotherapy and temozolomide as in phase I initiation course and cilengitide at a higher dose as in phase I initiation and maintenance courses. Patients are followed every 2 months. PROJECTED ACCRUAL: A total of 9-112 patients (9-18 for phase I and 94 [47 per treatment arm] for phase II) will be accrued for this study within 1.5-37 months
Trial information was received from ClinicalTrials.gov and was last updated in May 2013.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).