A Phase I/II Study to Evaluate the Safety and Tolerance of Escalating Doses of RSR13 Administered With a Fixed Dose of BCNU Every Six Weeks in Patients With Recurrent Malignant Glioma
18 Years
N/A
Both
Brain and Central Nervous System Tumors
Trial Information
A Phase I/II Study to Evaluate the Safety and Tolerance of Escalating Doses of RSR13 Administered With a Fixed Dose of BCNU Every Six Weeks in Patients With Recurrent Malignant Glioma
OBJECTIVES:
- Evaluate the safety and tolerability of escalating doses of efaproxiral (RSR13) when
administered concurrently with carmustine in patients with progressive or recurrent
malignant glioma.
- Determine the maximum tolerated dose (MTD) of RSR13 when administered with carmustine
in this patient population.
- Determine the pharmacokinetic profile of this regimen in these patients.
- Estimate the efficacy of this regimen at the MTD in these patients.
OUTLINE: This is a nonrandomized, open-label, multicenter, dose-escalation study of
efaproxiral (RSR13).
Patients receive RSR13 IV over 30 minutes followed 30 minutes later by carmustine IV over
1-2 hours on day 1. Treatment repeats every 6 weeks for a maximum of 6 courses in the
absence of unacceptable toxicity or disease progression.
Cohorts of 6-12 patients receive escalating doses of RSR13 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 or 5 of
12 patients experience dose-limiting toxicity. Once the MTD is determined, additional
patients are accrued to receive treatment with RSR13 and carmustine at the recommended phase
II dose.
Patients are followed at 6 weeks and then every 2 months thereafter.
PROJECTED ACCRUAL: A maximum of 48 patients will be accrued for the phase I portion of this
study. A maximum of 47 patients will be accrued for the phase II portion of this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed malignant glioma that is progressive or recurrent after
radiotherapy with or without chemotherapy
- Anaplastic astrocytoma
- Anaplastic oligodendroglioma
- Glioblastoma multiforme
- Prior low-grade glioma allowed provided progression has occurred after radiotherapy
with or without chemotherapy and then high-grade glioma is found on biopsy
- Measurable disease by serial MRI or CT scan
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
- Hemoglobin at least 10 g/dL
- Platelet count at least 100,000/mm^3
Hepatic:
- Bilirubin no greater than 2.0 mg/dL
- Alkaline phosphatase no greater than 3 times upper limit of normal (ULN)
- SGOT and SGPT no greater than 3 times ULN
Renal:
- Creatinine no greater than 2.0 mg/dL
Pulmonary:
- Resting oxygen saturation on room air at least 90% by pulse oximetry
- FVC, DLCO, and FEV_1 at least 50% of normal
Other:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No other serious concurrent medical illness that would preclude study compliance
- No other prior malignancy within the past 5 years except curatively treated basal
cell or squamous cell skin cancer or carcinoma in situ
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- At least 3 weeks since prior investigational biologics
Chemotherapy:
- See Disease Characteristics
- No prior nitrosoureas for glioma
- No more than 1 prior chemotherapy regimen
- At least 4 weeks since prior chemotherapy
- No prior efaproxiral
Endocrine therapy:
- Concurrent corticosteroids (e.g., dexamethasone) allowed
Radiotherapy:
- See Disease Characteristics
- At least 90 days since prior radiotherapy
Surgery:
- Not specified
Other:
- At least 3 weeks since other prior investigational drugs or devices
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Safety and tolerability
Safety Issue:
Yes
Principal Investigator
Pamela Z. New, MD
Investigator Role:
Study Chair
Investigator Affiliation:
The University of Texas Health Science Center, Houston
Authority:
United States: Federal Government
Study ID:
CDR0000067881
NCT ID:
NCT00005855
Start Date:
July 2000
Completion Date:
October 2006
Related Keywords:
- Brain and Central Nervous System Tumors
- adult glioblastoma
- adult anaplastic astrocytoma
- adult anaplastic oligodendroglioma
- recurrent adult brain tumor
- adult giant cell glioblastoma
- adult gliosarcoma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
- Glioma
Name | Location |
|---|---|
| University of Texas Health Science Center at San Antonio | San Antonio, Texas 78284-7811 |
| Abramson Cancer Center of the University of Pennsylvania | Philadelphia, Pennsylvania 19104-4283 |
| Massachusetts General Hospital Cancer Center | Boston, Massachusetts 02114 |
| University of Alabama at Birmingham Comprehensive Cancer Center | Birmingham, Alabama 35294-3300 |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
| Josephine Ford Cancer Center at Henry Ford Hospital | Detroit, Michigan 48202 |
| Winship Cancer Institute of Emory University | Atlanta, Georgia 30322 |
| Wake Forest University Comprehensive Cancer Center | Winston-Salem, North Carolina 27157-1096 |
| H. Lee Moffitt Cancer Center and Research Institute at University of South Florida | Tampa, Florida 33612 |
