An Open-Labeled, Non-Randomized Phase I Study Of Flavopiridol Administered With Irinotecan (CPT-11) In Patients With Advanced Solid Tumors
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Locations
- 1
Study Overview
Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of combining flavopiridol with irinotecan in treating patients who have locally advanced or metastatic solid tumors.
Detailed Description
OBJECTIVES:
- Determine the maximum tolerated dose of flavopiridol when combined with irinotecan in patients with advanced solid tumors.
- Determine the clinical pharmacokinetics of this regimen, as well as the plasma levels of the active metabolite SN-38 and metabolic product SN-38 glucuronide in these patients.
- Determine, in a preliminary manner, the therapeutic activity of this regimen in these patients.
- Determine the role of p21 relative to treatment response and apoptosis in these patients treated with this regimen.
OUTLINE: This is a dose-escalation, open-label, non-randomized study of flavopiridol.
Patients receive irinotecan IV over 30 minutes followed 7 hours later by flavopiridol IV over 1 hour on days 1, 8, 15, and 22. Treatment continues every 6 weeks for a minimum of 2 courses in the absence of disease progression or unacceptable toxicity. During the first week of the second course, patients receive flavopiridol alone on day 1 and irinotecan alone on day 2.
Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 or more of 6 patients in the initial cohort experience dose limiting toxicity during the first course of treatment. An additional 10 patients are treated at the MTD.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •DISEASE CHARACTERISTICS:
- •Histologically proven locally advanced or metastatic solid tumor that is refractory to standard therapy or for which no standard therapy exists
- •Eligible for treatment at the maximum tolerated dose only if disease accessible for tissue biopsy by Tru-Cut, CT guidance, or endoscopy
- •Pleural effusions or abdominal ascites do not constitute adequate tissue for biopsy
- •No known CNS metastasis or primary CNS tumor
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status:
- •Karnofsky 60-100%
- •Life expectancy:
- •Not specified
- •Hematopoietic:
- •WBC at least 3,500/mm^3
- •Total neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Bilirubin no greater than 1.5 mg/dL
- •SGOT and SGPT no greater than 2.5 times upper limit of normal
- •Creatinine no greater than 1.5 mg/dL
- •Cardiovascular:
- •No cardiac arrhythmias, congestive heart failure, or myocardial infarction within the past 6 months
- •Not pregnant or nursing (during and for at least 2 months after study)
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for at least 2 months after study
- •No concurrent serious or uncontrolled infection
- •HIV negative
- •No other medical condition that would preclude study participation
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •At least 4 weeks since prior immunotherapy and recovered
- •Chemotherapy:
- •At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- •Prior irinotecan allowed
- •Endocrine therapy:
- •Not specified
- •Radiotherapy:
- •At least 4 weeks since prior radiotherapy and recovered
- •See Disease Characteristics
- •Recovered from prior therapy
- •No other concurrent investigational medication
- •No concurrent vitamins (except a single multivitamin tablet), antioxidants, or herbal preparations or supplements
- •No concurrent subcutaneous heparin or heparinoids
Exclusion Criteria
- Not provided