Combination Chemotherapy in Treating Patients With Advanced Solid Tumors
Unspecified Adult Solid Tumor, Protocol Specific
Drug: irinotecan hydrochloride
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-Labeled, Non-Randomized Phase I Study of Alvocidib (Flavopiridol) Administered With Irinotecan (CPT-11) and Cisplatin in Patients With Advanced Solid Tumors|
- MTD alvocidib when administered in conjunction with irinotecan hydrochloride and cisplatin [ Time Frame: Course 1 ] [ Designated as safety issue: Yes ]Defined as the dose one level below the dose at which two or more of the patients in the initial cohort experience dose limiting toxicity (DLT) during the first treatment course. DLT is defined as the occurrence of Grade 4 hematologic toxicity, Grade 3 or 4 non-hematologic toxicity including diarrhea despite antidiarrheal prophylaxis, or any delay in treatment resulting in less than 2 treatments in 3 weeks.
- Clinical pharmacokinetics of the regimen [ Time Frame: Week 1 of courses 1 and 2 ] [ Designated as safety issue: Yes ]
- Therapeutic activity of alvocidib in combination with irinotecan hydrochloride in patients with advanced solid tumors [ Time Frame: After 2 courses of treatment ] [ Designated as safety issue: Yes ]Evaluated using Response Evaluation Criteria In Solid Tumors (RECIST).
- Safety and tolerability [ Time Frame: Weekly ] [ Designated as safety issue: Yes ]Evaluated using the National Cancer Institute (NCI) Common Toxicity Criteria. Tabulated individually, and summarized by body system, according to dosage of study medication.
|Study Start Date:||July 2002|
|Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
Experimental: Treatment (chemotherapy)
Patients are stratified according to the number of prior treatment regimens (0 or 1 vs more than 1). Patients receive irinotecan hydrochloride IV over 30 minutes followed immediately by cisplatin IV over 30 minutes followed 7 hours later by alvocidib IV over 1-4.5 hours weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Other Names:Drug: irinotecan hydrochloride
Other Names:Drug: cisplatin
I. Determine the maximum tolerated dose of flavopiridol (alvocidib), irinotecan (irinotecan hydrochloride), and cisplatin in patients with advanced solid tumors.
II. Determine the clinical pharmacokinetics of this regimen in these patients. III. Determine, preliminarily, the therapeutic activity of this regimen in these patients.
OUTLINE: This is a dose-escalation study.
Patients are stratified according to the number of prior treatment regimens (0 or 1 vs more than 1). Patients receive irinotecan hydrochloride intravenously (IV) over 30 minutes followed immediately by cisplatin IV over 30 minutes followed 7 hours later by alvocidib IV over 1-4.5 hours weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of cisplatin, alvocidib, and irinotecan hydrochloride until the maximum tolerated dose (MTD) of each is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 12 additional patients are treated at the recommended phase II dose.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00046917
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Manish Shah||Memorial Sloan Kettering Cancer Center|