A Phase I/II Trial of EMD 121974 for Treatment of Patients With Recurrent Anaplastic Gliomas
18 Years
N/A
Both
Brain and Central Nervous System Tumors
Trial Information
A Phase I/II Trial of EMD 121974 for Treatment of Patients With Recurrent Anaplastic Gliomas
OBJECTIVES:
- Determine the maximum tolerated dose and dose-limiting toxicity of EMD 121974 in
patients with progressive or recurrent malignant glioma.
- Determine the 6-month progression-free survival, clinical response rate, duration of
progression-free survival, and overall survival in patients treated with this drug.
- Determine the effects of this drug on tumor perfusion, measured with magnetic resonance
perfusion scan, and markers for angiogenesis in these patients.
OUTLINE: This is a dose-escalation, multicenter study.
Patients receive EMD 121974 IV over 1 hour twice weekly. Courses repeat every 4 weeks in the
absence of disease progression or unacceptable toxicity.
Cohorts of 6-12 patients receive escalating doses of EMD 121974 until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which more than 2
of 6 or 4 of 12 patients experience dose-limiting toxicity. Once the MTD is determined,
additional patients are treated at the MTD.
Patients are followed every 2 months.
PROJECTED ACCRUAL: A minimum of 6 patients will be accrued for phase I of this study within
2-3 months. A total of 23-38 patients will be accrued for phase II of this study within 5-10
months.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed malignant glioma that is progressive or recurrent after
radiotherapy and/or chemotherapy
- Eligible subtypes:
- Anaplastic astrocytoma
- Anaplastic oligodendroglioma
- Glioblastoma multiforme
- Prior low-grade glioma that has progressed to a high-grade glioma (by biopsy)
after radiotherapy and/or chemotherapy allowed
- Measurable disease by volumetric and magnetic resonance perfusion scan
- Prior biopsy or resection of recurrent brain tumor allowed
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- Karnofsky 60-100%
Life expectancy:
- Not specified
Hematopoietic:
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
Hepatic:
- Bilirubin normal
- Transaminases no greater than 2.5 times upper limit of normal
Renal:
- Creatinine no greater than 1.5 mg/dL OR
- Creatinine clearance at least 60 mL/min
Cardiovascular:
- No advanced coronary artery disease
Other:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No serious concurrent infection or medical illness that would preclude study
- No other malignancy within the past 5 years except curatively treated carcinoma in
situ or basal cell skin cancer
- No history of wound healing disorders
- No peptic ulcer disease within the past year
- Mini mental score of at least 15
- Willing and able to undergo MRI
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- No concurrent filgrastim (G-CSF)
Chemotherapy:
- See Disease Characteristics
- At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
- No more than 2 prior chemotherapy regimens
Endocrine therapy:
- Prior corticosteroids allowed if on stable dose for at least 5 days prior to study
- Concurrent corticosteroids (e.g., dexamethasone) allowed as clinically needed
Radiotherapy:
- See Disease Characteristics
- At least 3 months since prior radiotherapy and recovered
Surgery:
- See Disease Characteristics
- At least 1 week since prior surgery and recovered
- No concurrent elective surgery or dental extractions
Other:
- No other concurrent investigational agents
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Louis B. Nabors, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of Alabama at Birmingham
Authority:
United States: Federal Government
Study ID:
CDR0000068098
NCT ID:
NCT00006093
Start Date:
September 2000
Completion Date:
October 2006
Related Keywords:
- Brain and Central Nervous System Tumors
- recurrent adult brain tumor
- adult glioblastoma
- adult anaplastic astrocytoma
- adult anaplastic oligodendroglioma
- adult giant cell glioblastoma
- adult gliosarcoma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
Name | Location |
|---|---|
| H. Lee Moffitt Cancer Center and Research Institute | Tampa, Florida 33612 |
| Emory University Hospital - Atlanta | Atlanta, Georgia 30322 |
| University of Pennsylvania Cancer Center | Philadelphia, Pennsylvania 19104 |
| University of Texas Health Science Center at San Antonio | San Antonio, Texas 78284-7811 |
| Massachusetts General Hospital Cancer Center | Boston, Massachusetts 02114 |
| University of Alabama at Birmingham Comprehensive Cancer Center | Birmingham, Alabama 35294-3300 |
| Comprehensive Cancer Center at Wake Forest University | Winston-Salem, North Carolina 27157-1082 |
| Henry Ford Hospital | Detroit, Michigan 48202 |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
| Cleveland Clinic Taussig Cancer Center | Cleveland, Ohio 44195 |
