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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


Phase 1
18 Years
N/A
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

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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 CenterNew York, New York  10021