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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00085254
First received: June 10, 2004
Last updated: January 28, 2016
Last verified: October 2015
  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

Condition Intervention Phase
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Drug: cilengitide
Drug: temozolomide
Radiation: radiation therapy
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1
Phase 2

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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Dose Limiting Toxicities of EMD + RT and TMZ [ Time Frame: 10 weeks ] [ Designated as safety issue: Yes ]

    pts will be evaluated from first dose through end of initiation cycle. (6 weeks of RT+TMZ +EMD and 4 weeks of EMD alone) to review dose limiting toxicity (DLT) using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)

    DLT defined as: Known TMZ hematological toxicities will not be considered dose limiting.

    Nonhematological toxicities Grades 3-4 severity (except nausea and vomiting without sufficient antiemetic prophylaxis)


  • Maximum Tolerated or Tolerable Dose (MTD) - 3 Pre-defined Doses [ Time Frame: 10 weeks ] [ Designated as safety issue: Yes ]

    pts will be evaluated from first dose through end of initiation cycle. (6 weeks of RT+TMZ +EMD and 4 weeks of EMD alone) to review any dose limiting toxicity (DLT) using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (safety run-in)

    DLT defined as: Known TMZ hematological toxicities will not be considered dose limiting.

    cohorts at these 3 defined doses: 500mg, 1000mg and 2000mg MTD defined as: dose producing DLT in 2 out of 6 patients or dose level below the dose which produced DLT in >/= 2 out of 3 patients, or in >/= 3 out of 6 patients If no MTD (maximum tolerable dose) was defined through 3 steps of dose escalation, phase 2 will proceed with a randomized treatment allocation of the two pre-specified dosage arms: low dose; 500mg and high dose; 2000mg


  • Overall Survival (Phase II) [ Time Frame: up to 36 months ] [ Designated as safety issue: No ]
    The overall survival is calculated from time of histological diagnosis to death occurance - median based on all 112 patients, all dose levels


Secondary Outcome Measures:
  • Overall Survival Based on Dose Level - Phase 2 [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    survival calculated from date of initial histologic diagnosis and occurence of death. Pts at 500mg dose compared against Pts treated at 2000mg dose. Calculated using median

  • Frequency of Hematologic and Nonhematologic Adverse Events [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    The proportion of patients with grade 3 and grade 4 hematologic and non hematologic adverse events per CTCAE 4.0


Enrollment: 112
Study Start Date: April 2005
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Drug: cilengitide
Given IV
Other Name: EMD 121974
Drug: temozolomide
Given orally
Other Names:
  • SCH 52365
  • Temodal
  • Temodar
  • TMZ
Radiation: radiation therapy
Undergo radiotherapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
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

Drug: cilengitide
Given IV
Other Name: EMD 121974
Drug: temozolomide
Given orally
Other Names:
  • SCH 52365
  • Temodal
  • Temodar
  • TMZ
Radiation: radiation therapy
Undergo radiotherapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
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

Drug: cilengitide
Given IV
Other Name: EMD 121974
Drug: temozolomide
Given orally
Other Names:
  • SCH 52365
  • Temodal
  • Temodar
  • TMZ
Radiation: radiation therapy
Undergo radiotherapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00085254

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, North Carolina
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Louis Nabors, MD National Cancer Institute (NCI)
  More Information

Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00085254     History of Changes
Other Study ID Numbers: NCI-2012-02932  NABTT 0306  CDR0000368451  U01CA062475 
Study First Received: June 10, 2004
Results First Received: May 5, 2015
Last Updated: January 28, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Glioblastoma
Gliosarcoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 27, 2016