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Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

Study Purpose

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

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT00085254
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

National Cancer Institute (NCI)
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Louis Nabors, MD
Principal Investigator Affiliation National Cancer Institute (NCI)
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

NIH
Overall Status Completed
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma
Additional Details

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.
(Safety Run-In)
  • 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, safety run-in study of cilengitide followed by a randomized phase II study. Safety Run-In: 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 (3 Pre-defined study dose levels are defined as: 500, 1000 and 2000mg). The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity. If no MTD (maximum tolerable dose) is defined through three steps of the dose escalation process, we will pursue the phase II safety/efficacy study with randomized treatment allocation. Patients will be randomized into one of two pre-specified treatment dosage arms, 500mg group or 2000mg group. PHASE II: Patients are stratified according to age (50 and under vs.#46;over 50), Karnofsky performance score (60%-80% vs.#46;90%-100%), and tumor status (measurable vs.#46;nonmeasurable). Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive radiotherapy and temozolomide as in safety run-in initiation course and cilengitide at the lower dose as in safety run-in initiation and maintenance courses. ARM II: Patients receive radiotherapy and temozolomide as in safety run-in initiation course and cilengitide at the higher dose as in safety run-in initiation and maintenance courses. Patients are followed every 2 months. PROJECTED ACCRUAL: A total of 9-112 patients (9-18 for safety run-in and 94 [47 per treatment arm] for phase II) will be accrued for this study within 1.5-37 months

Arms & Interventions

Arms

Experimental: Arm 1 (Safety Run In)

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. Doses of cilengitide: 500mg, 1000mg and 2000mg Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study

Experimental: Phase II (Arm1-500mg)

INITIATION COURSE: Patients receive cilengitide (500mg) 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 (500mg) 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. cilengitide, Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study

Experimental: Phase II (Arm 2 -2000mg)

INITIATION COURSE: Patients receive cilengitide (2000mg) 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 (2000mg) 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. cilengitide,Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study

Interventions

Drug: - cilengitide

Given IV

Drug: - temozolomide

Given orally

Radiation: - radiation therapy

Undergo radiotherapy

Other: - laboratory biomarker analysis

Correlative studies

Other: - pharmacological study

Correlative studies

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

University of Alabama at Birmingham, Birmingham, Alabama

Status

Address

University of Alabama at Birmingham

Birmingham, Alabama, 35294

Emory University, Atlanta, Georgia

Status

Address

Emory University

Atlanta, Georgia, 30322

Johns Hopkins University, Baltimore, Maryland

Status

Address

Johns Hopkins University

Baltimore, Maryland, 21287

Massachusetts General Hospital, Boston, Massachusetts

Status

Address

Massachusetts General Hospital

Boston, Massachusetts, 02114

Henry Ford Hospital, Detroit, Michigan

Status

Address

Henry Ford Hospital

Detroit, Michigan, 48202

Wake Forest University Health Sciences, Winston-Salem, North Carolina

Status

Address

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157

Cleveland Clinic Foundation, Cleveland, Ohio

Status

Address

Cleveland Clinic Foundation

Cleveland, Ohio, 44195

University of Pennsylvania, Philadelphia, Pennsylvania

Status

Address

University of Pennsylvania

Philadelphia, Pennsylvania, 19104