Trial Information

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

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