A Phase I Study of the Cyclin-Dependent Kinase (CDK)/Protein Kinase C (PKC) Inhibitor UCN-01 (NSC 638850) in Combination With 5-Fluorouracil in Patients With Advanced Solid Tumors
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I Study of the Cyclin-Dependent Kinase (CDK)/Protein Kinase C (PKC) Inhibitor UCN-01 (NSC 638850) in Combination With 5-Fluorouracil in Patients With Advanced Solid Tumors
OBJECTIVES:
- Determine the maximum tolerated dose, dose limiting toxicity, and toxicity profile of
fluorouracil with UCN-01 in patients with advanced or refractory solid tumors.
- Assess the clinical pharmacokinetics of this regimen and correlate with observed
toxicities in these patients.
- Obtain preliminary data on the therapeutic activity of this regimen in these patients.
OUTLINE: This is a dose escalation study of fluorouracil.
Patients receive fluorouracil IV over 24 hours on days 1, 8, 15, and 22. Patients receive an
initial dose of UCN-01 IV over 72 hours beginning on day 2 during course 1 and then
maintenance UCN-01 IV over 36 hours beginning on day 2 during subsequent courses. Treatment
repeats every 4 weeks for at least 2 courses in the absence of disease progression or
unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of fluorouracil 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.
PROJECTED ACCRUAL: Approximately 6-48 patients will be accrued for this study within
approximately 14 months.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed solid tumor that is refractory to standard therapy or for
which no standard therapy exists
- Measurable or evaluable disease
- No CNS metastasis or primary CNS malignancy
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- Karnofsky 60-100%
Life expectancy:
- Not specified
Hematopoietic:
- WBC greater than 3,500/mm^3
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
Hepatic:
- Bilirubin no greater than 1.5 mg/dL
- SGOT and 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 history of coronary artery disease documented by prior myocardial infarction,
angiography, or coronary-artery bypass grafting
- No cardiac arrhythmias or congestive heart failure within the past 6 months
- Stable atrial fibrillation on standard treatment allowed at discretion of
investigator
Pulmonary:
- DLCO at least 60% of predicted
Other:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 2 months after study
- No active serious or uncontrolled infection
- HIV negative
- No diabetes
- No other medical condition that would preclude study
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
Biologic therapy:
- At least 4 weeks since prior immunotherapy and recovered
Chemotherapy:
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin)
and recovered
- Prior fluorouracil allowed
Endocrine therapy:
- Not specified
Radiotherapy:
- No prior mediastinal radiotherapy
- At least 4 weeks since prior radiotherapy and recovered
Surgery:
- Not specified
Other:
- No concurrent anticonvulsant medications
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Gary K. Schwartz, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Federal Government
Study ID:
99-024
NCT ID:
NCT00004059
Start Date:
July 1999
Completion Date:
September 2002
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
- Neoplasms
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
