Combination Chemotherapy in Treating Patients With Advanced Solid Tumors

NCT ID: NCT00046917

Last Updated: 2014-02-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-07-31

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

alvocidib

Intervention Type: DRUG

Given IV

irinotecan hydrochloride

Intervention Type: DRUG

Given IV

cisplatin

Intervention Type: DRUG

Given IV

Interventions

alvocidib

Given IV

Intervention Type: DRUG

irinotecan hydrochloride

Given IV

Intervention Type: DRUG

cisplatin

Given IV

Intervention Type: DRUG

Other Intervention Names

FLAVO; flavopiridol; HMR 1275; L-868275; Campto; Camptosar; CPT-11; irinotecan; U-101440E; CACP; CDDP; CPDD; DDP

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Manish Shah

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

Other Identifiers

NCI-2009-00023

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-5700

Identifier Type: -

Identifier Source: secondary_id

CDR0000257034

Identifier Type: -

Identifier Source: secondary_id

MSKCC-02043

Identifier Type: -

Identifier Source: secondary_id

02-043A

Identifier Type: OTHER

Identifier Source: secondary_id

5700

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA008748

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01CA067819

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA069856

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00023

Identifier Type: -

Identifier Source: org_study_id

NCT01645462

Identifier Type: -

Identifier Source: nct_alias