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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


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma

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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


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome 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)

Outcome Time Frame:

28 days

Safety Issue:

Yes

Principal Investigator

Louis Nabors

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02932

NCT ID:

NCT00085254

Start Date:

April 2005

Completion Date:

Related Keywords:

  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Glioblastoma
  • Gliosarcoma

Name

Location

Johns Hopkins UniversityBaltimore, Maryland  21205
Cleveland Clinic FoundationCleveland, Ohio  44195
Abramson Cancer Center of the University of PennsylvaniaPhiladelphia, Pennsylvania  19104-4283
Massachusetts General Hospital Cancer CenterBoston, Massachusetts  02114
Henry Ford HospitalDetroit, Michigan  48202
Massachusetts General HospitalBoston, Massachusetts  02114-2617
University of Alabama at BirminghamBirmingham, Alabama  35294-3300
Emory UniversityAtlanta, Georgia  30322
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
Adult Brain Tumor ConsortiumBaltimore, Maryland  21231-1000