Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
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| ClinicalTrials.gov Identifier: NCT00085254 |
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Recruitment Status :
Completed
First Posted : June 11, 2004
Results First Posted : February 25, 2016
Last Update Posted : February 25, 2016
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| Condition or disease | Intervention/treatment | 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 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 112 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (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 |
| Study Start Date : | April 2005 |
| Actual Primary Completion Date : | November 2012 |
| Actual Study Completion Date : | November 2012 |
| Arm | Intervention/treatment |
|---|---|
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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:
Radiation: radiation therapy Undergo radiotherapy
Other Names:
Other: laboratory biomarker analysis Correlative studies Other: pharmacological study Correlative studies
Other Name: pharmacological studies |
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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:
Radiation: radiation therapy Undergo radiotherapy
Other Names:
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:
Radiation: radiation therapy Undergo radiotherapy
Other Names:
Other: laboratory biomarker analysis Correlative studies Other: pharmacological study Correlative studies
Other Name: pharmacological studies |
- Dose Limiting Toxicities of EMD + RT and TMZ [ Time Frame: 10 weeks ]
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 ]
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 ]The overall survival is calculated from time of histological diagnosis to death occurance - median based on all 112 patients, all dose levels
- Overall Survival Based on Dose Level - Phase 2 [ Time Frame: Up to 3 years ]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 ]The proportion of patients with grade 3 and grade 4 hematologic and non hematologic adverse events per CTCAE 4.0
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, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00085254
| 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 | |
| Principal Investigator: | Louis Nabors, MD | National Cancer Institute (NCI) |
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00085254 |
| Other Study ID Numbers: |
NCI-2012-02932 NABTT 0306 CDR0000368451 U01CA062475 ( U.S. NIH Grant/Contract ) |
| First Posted: | June 11, 2004 Key Record Dates |
| Results First Posted: | February 25, 2016 |
| Last Update Posted: | February 25, 2016 |
| Last Verified: | October 2015 |
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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 Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents |