A Phase I/II Study of Col-3 Administered on a Continuous Daily Oral Schedule in Patients With Recurrent High-Grade Astrocytoma
18 Years
N/A
Both
Brain and Central Nervous System Tumors
Trial Information
A Phase I/II Study of Col-3 Administered on a Continuous Daily Oral Schedule in Patients With Recurrent High-Grade Astrocytoma
OBJECTIVES:
- Determine the maximum tolerated dose, dose limiting toxicity, and safety profile of
oral COL-3 alone or when combined with anticonvulsants known to be metabolized by
CYP450 in patients with progressive or recurrent high grade anaplastic astrocytoma,
anaplastic oligodendroglioma, or glioblastoma multiforme.
- Define the pharmacokinetics and pharmacodynamics of COL-3 on this schedule and
determine the effects of hepatic enzyme inducing drugs, such as anticonvulsants, on the
pharmacokinetics.
- Determine the response rate, disease free survival, and survival in patients treated
with this regimen.
OUTLINE: This is a dose-escalation, multicenter study of COL-3. Patients are stratified by
anticonvulsant (anticonvulsants that cause induction of CYP450 vs anticonvulsants that cause
modest or no induction of CYP450 or no anticonvulsant).
- Phase I: Patients receive oral COL-3 daily. Treatment repeats every 4 weeks in the
absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of COL-3 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients
experience dose limiting toxicity.
- Phase II: Patients receive oral COL-3 daily at the MTD from the phase I portion of this
study.
Patients are followed every 2 months until death.
PROJECTED ACCRUAL: A total of 15-18 patients will be accrued for phase I of the study and a
total of 35 patients will be accrued for phase II of the study at a rate of 3 patients per
month.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically proven high grade glioma that is progressive or recurrent following
radiotherapy or chemotherapy
- Anaplastic astrocytoma
- Anaplastic oligodendroglioma
- Glioblastoma multiforme
- Prior low grade glioma that has progressed to high grade glioma following
radiotherapy and/or chemotherapy allowed
- Measurable disease by 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
- Platelet count at least 100,000/mm^3
Hepatic:
- Bilirubin normal
- SGOT or SGPT no greater than 2.5 times upper limit of normal
Renal:
- Creatinine no greater than 1.5 mg/dL OR
- Creatinine clearance greater than 60 mL/min
Cardiovascular:
- No myocardial infarction, stroke, or congestive heart failure within the past 3
months
Other:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 1 month after study
- No serious active infection or medical illness that would preclude compliance
- HIV negative
- No history of gastrointestinal disorders that would interfere with absorption of
study drug
- No other malignancy within the past 5 years except curatively treated carcinoma in
situ of the cervix or breast, or basal cell or squamous cell skin cancer
- No hypersensitivity to tetracyclines or its derivatives
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- No concurrent filgrastim (G-CSF)
Chemotherapy:
- At least 4 weeks since prior chemotherapy (6 weeks since prior nitrosoureas) and
recovered
- No more than 2 prior chemotherapy regimens
Endocrine therapy:
- Not specified
Radiotherapy:
- No prior large field radiotherapy (greater than 20% of total bone marrow)
- At least 3 months since other prior radiotherapy and recovered
Surgery:
- No prior major upper gastrointestinal surgery
- At least 14 days since other prior major surgery
Other:
- No other concurrent investigational agents
- No prolonged sun exposure
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Pamela Z. New, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of Texas Health Science Center at San Antonio
Authority:
United States: Federal Government
Study ID:
CDR0000067379
NCT ID:
NCT00004147
Start Date:
July 2000
Completion Date:
November 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
- Astrocytoma
- Brain Neoplasms
- 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 |
