An Open-Label, Non-Randomized Phase I Study of the Protein Kinase C Inhibitor Flavopiridol Administered in Combination With Paclitaxel in Patients With Advanced Solid Tumors
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
An Open-Label, Non-Randomized Phase I Study of the Protein Kinase C Inhibitor Flavopiridol Administered in Combination With Paclitaxel in Patients With Advanced Solid Tumors
OBJECTIVES: I. Determine the maximum tolerated dose of flavopiridol when administered in
combination with paclitaxel and cisplatin in patients with refractory adult solid tumors.
II. Investigate the clinical pharmacokinetics of intravenous flavopiridol when administered
in combination with paclitaxel in these patients. III. Obtain preliminary data on the
therapeutic activity of flavopiridol when administered in combination with paclitaxel in
these patients. IV. Evaluate surrogate markers of activity such as inhibition of PKC or CDK1
in these patients.
OUTLINE: This is an open label, dose escalation study. Patients receive paclitaxel IV over 3
hours on day 1. On day 2, patients receive cisplatin IV over 20 minutes followed by a 24
hour infusion of flavopiridol. Courses are repeated every 21 days in the absence of disease
progression or unacceptable toxicity. Sequential dose escalation of flavopiridol is followed
by sequential dose escalation of cisplatin. Dose escalation in cohorts of 3-6 patients each
continues 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. Patients are
followed every 6 weeks.
PROJECTED ACCRUAL: Approximately 46-73 patients will be accrued for this study within 6 more
months.
Inclusion Criteria
DISEASE CHARACTERISTICS: Histologically proven solid tumors that are refractory or
recurrent -No CNS primary or metastatic disease
PATIENT CHARACTERISTICS: Age: 18 and over Performance Status: Karnofsky at least 60%
Hematopoietic: WBC at least 3,500/mm3 Absolute neutrophil count at least 1,500/mm3
Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 mg/dL AST and
ALT no greater than 2.5 times upper limit of normal Renal: Creatinine no greater than 1.5
mg/dL Cardiovascular: At least 6 months since prior cardiac arrhythmias, myocardial
infarction, or congestive heart failure Other: Not pregnant or nursing Effective
contraceptive method must be used for 2 months after study completion Not HIV positive No
uncontrolled or serious infection No pre-existing grade 3 or greater neurotoxicity Must be
mentally capable of understanding the explanation of the study
PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior immunotherapy
Chemotherapy: At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or
mitomycin) Endocrine therapy: Not specified Radiotherapy: At least 4 weeks since prior
radiotherapy Surgery: Not specified Other: No presence of toxic effects from prior therapy
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:
96-077
NCT ID:
NCT00003004
Start Date:
July 1997
Completion Date:
October 2001
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 |
