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An Open-Labeled, Non-Randomized Phase I Study of Alvocidib (Flavopiridol) Administered With Irinotecan (CPT-11) and Cisplatin in Patients With Advanced Solid Tumors

Phase 1
18 Years
Not Enrolling
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

An Open-Labeled, Non-Randomized Phase I Study of Alvocidib (Flavopiridol) Administered With Irinotecan (CPT-11) and Cisplatin in Patients With Advanced Solid Tumors


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.

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

- 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

- No other concurrent investigational drugs

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD alvocidib when administered in conjunction with irinotecan hydrochloride and cisplatin

Outcome Description:

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.

Outcome Time Frame:

Course 1

Safety Issue:


Principal Investigator

Manish Shah

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

July 2002

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • Neoplasms



Memorial Sloan Kettering Cancer Center New York, New York  10021