Clinical trial NCT00046917: Combination Chemotherapy in Treating Patients With Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase I trial to study the effectiveness of combining alvocidib, irinotecan hydrochloride, and cisplatin in treating patients who have advanced solid tumors. 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.

Detailed description: OBJECTIVES:

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.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed locally advanced or metastatic solid tumor that is refractory to standard therapy or for which no standard therapy exists
* Evaluable disease
* No previously untreated CNS metastasis
* No primary CNS tumors
* Performance status - Karnofsky 60-100%
* Performance status - ECOG 0-2
* Not specified
* WBC at least 3,000/mm\^3
* Neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3
* Bilirubin no greater than 2.0 mg/dL
* AST and ALT no greater than 3 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
* Creatinine no greater than 1.5 mg/dL
* Creatinine clearance at least 60 mL/min
* No cardiac arrhythmia
* No congestive heart failure
* No myocardial infarction within the past 6 months
* HIV negative
* No neuropathy grade 2 or greater
* No serious or uncontrolled infection
* No other medical condition or reason that would preclude study participation
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for at least 2 months after study participation
* At least 4 weeks since prior immunotherapy
* At least 1 week since prior irinotecan and cisplatin alone
* At least 4 weeks since other prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
* Not specified
* At least 4 weeks since prior radiotherapy
* Not specified
* Recovered from all prior therapy
* No concurrent vitamins, antioxidants, or herbal supplements except a daily multivitamin
* No other concurrent investigational drugs

Primary outcomes:
measure: MTD alvocidib when administered in conjunction with irinotecan hydrochloride and cisplatin
timeFrame: Course 1
Secondary outcomes:
measure: Clinical pharmacokinetics of the regimen
timeFrame: Week 1 of courses 1 and 2
measure: Therapeutic activity of alvocidib in combination with irinotecan hydrochloride in patients with advanced solid tumors
timeFrame: After 2 courses of treatment
measure: Safety and tolerability
timeFrame: Weekly
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Manish Shah
role: PRINCIPAL_INVESTIGATOR
References: