The Pharmacokinetic and Safety Profile of UCN-01 in Combination With Irinotecan in Solid Tumors (Primarily Lung, Ovarian and GI Cancers)
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
The Pharmacokinetic and Safety Profile of UCN-01 in Combination With Irinotecan in Solid Tumors (Primarily Lung, Ovarian and GI Cancers)
OBJECTIVES:
- Determine the maximum tolerated dose and recommended phase II dose of UCN-01 and
irinotecan in patients with advanced solid tumors, primarily lung, ovarian, and
gastrointestinal tumors.
- Determine the acute and chronic toxicity profile of this regimen in these patients.
- Determine the pharmacokinetics of this regimen in these patients.
- Determine, preliminarily, the anti-tumor effect of this regimen in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive UCN-01 IV over 3 hours on day 1 and irinotecan IV over 90 minutes on days 1
and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable
toxicity.
Cohorts of 3-6 patients receive escalating doses of UCN-01 and irinotecan until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2
of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated
at the recommended phase II dose.
Patients are followed at 1 month.
PROJECTED ACCRUAL: Approximately 20-30 patients will be accrued for this study within 7-15
months.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed malignancy that is metastatic or unresectable and for which
standard curative or palliative therapy does not exist or is no longer effective
- Gastrointestinal, lung, and ovarian malignancies are given priority
- No brain metastases
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2 OR
- Karnofsky 60-100%
Life expectancy
- More than 3 months
Hematopoietic
- WBC at least 3,000/mm^3
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
Hepatic
- Bilirubin normal
- AST/ALT no greater than 2.5 times upper limit of normal (ULN)
Renal
- Creatinine normal OR
- Creatinine clearance at least 60 mL/min
Cardiovascular
- No symptomatic coronary artery disease
- No symptomatic cardiac dysfunction
- No symptoms suggestive of coronary artery disease
- LVEF at least 50%
Pulmonary
- No symptomatic pulmonary dysfunction
- FEV_1 greater than 75% of predicted
- DLCO greater than 75% of predicted
Other
- Amylase no greater than 2 times ULN
- No other concurrent uncontrolled illness
- No ongoing or active infection
- No psychiatric illness or social situation that would preclude study compliance
- No diabetes mellitus or random glucose more than 200 mg/dL
- No prior allergic reaction attributed to compounds of similar biological or chemical
composition to UCN-01 or irinotecan (including rash and systemic allergic reaction
causing hypotension and respiratory distress)
- No chronic diarrhea (more than 5 stools/day)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception for 14 days before, during, and for
at least 30 days after study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and
recovered
- Prior UCN-01 and irinotecan allowed
Endocrine therapy
- Not specified
Radiotherapy
- At least 4 weeks since prior radiotherapy and recovered
- No prior mediastinal radiation
Surgery
- Not specified
Other
- At least 14 days since prior warfarin
- No concurrent warfarin unless required for maintaining patency of existing, permanent
IV catheters
- No concurrent commercial or other investigational anticancer agents or therapies
- No concurrent combination antiretroviral therapy for HIV-positive patients
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Ross C. Donehower, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Sidney Kimmel Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
JHOC-J0173, CDR0000257566
NCT ID:
NCT00047242
Start Date:
August 2002
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
- Neoplasms
Name | Location |
|---|---|
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
