Combination Chemotherapy in Treating Patients With Locally Advanced or Metastatic Solid Tumors

NCT ID: NCT00042874

Last Updated: 2013-06-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 77 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-05-31

Brief Summary

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. This phase I trial is studying the side effects and best dose of combination chemotherapy in treating patients with locally advanced or metastatic solid tumors.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of flavopiridol (alvocidib) when administered with irinotecan hydrochloride, fluorouracil, and leucovorin calcium in patients with locally advanced or metastatic solid tumors.

II. Determine the clinical pharmacokinetics of fluorouracil when administered in this regimen in these patients.

III. Determine, preliminarily, the therapeutic activity of this regimen in these patients.Correlate the role of p21 and Drg1 with apoptosis and treatment response in patients receiving this regimen.

OUTLINE: This is a dose-escalation study of alvocidib and fluorouracil (5-FU).

Patients receive irinotecan hydrochloride IV over 90 minutes followed 5 hours later by leucovorin calcium IV over 2 hours and alvocidib IV over 1 hour immediately followed by 5-FU IV continuously over 48 hours beginning on day 1 of weeks 1, 3, and 5. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of alvocidib and 5-FU until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Ten additional patients are treated at the MTD.

PROJECTED ACCRUAL: A total of 27-77 patients will be accrued for this study within 11-38 months.

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 (combination chemotherapy)

Patients receive irinotecan hydrochloride IV over 90 minutes followed 5 hours later by leucovorin calcium IV over 2 hours and alvocidib IV over 1 hour immediately followed by 5-FU IV continuously over 48 hours beginning on day 1 of weeks 1, 3, and 5. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of alvocidib and 5-FU until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Ten additional patients are treated at the MTD.

Group Type: EXPERIMENTAL

alvocidib

Intervention Type: DRUG

Given IV

irinotecan hydrochloride

Intervention Type: DRUG

Given IV

fluorouracil

Intervention Type: DRUG

Given IV

leucovorin calcium

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

alvocidib

Given IV

Intervention Type: DRUG

irinotecan hydrochloride

Given IV

Intervention Type: DRUG

fluorouracil

Given IV

Intervention Type: DRUG

leucovorin calcium

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

FLAVO; flavopiridol; HMR 1275; L-868275; Campto; Camptosar; CPT-11; irinotecan; U-101440E; 5-fluorouracil; 5-Fluracil; 5-FU; CF; CFR; LV

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed locally advanced or metastatic solid tumor

• Refractory to standard therapy or for which there is no standard therapy
• Preference given to colorectal cancer, upper gastrointestinal cancer, or neuroendocrine tumors
• Evaluable disease
• No CNS metastases or primary CNS malignancy
• Performance status - Karnofsky 60-100%
• WBC at least 3,500/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Bilirubin no greater than 1.5 mg/dL
• AST and ALT no greater than 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
• Creatinine no greater than 1.5 mg/dL
• No history of cardiac arrhythmia
• No congestive heart failure
• No myocardial infarction within the past 6 months
• No prior grade 3 or 4 diarrhea secondary to irinotecan, despite optimal antidiarrheal prophylaxis
• HIV negative
• 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 2 weeks since prior immunotherapy
• No more than 2 prior chemotherapy regimens unless there is no evidence of significant myelotoxicity as determined by the primary investigator
• At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin)
• Prior irinotecan and fluorouracil allowed
• At least 2 weeks since prior radiotherapy
• Recovered from all prior therapy
• No other concurrent investigational medications
• No concurrent vitamins, antioxidants, or herbal preparations or supplements except a single daily multivitamin

• 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

Gary K. Schwartz

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

5757

Identifier Type: -

Identifier Source: secondary_id

NCI-5757

Identifier Type: -

Identifier Source: secondary_id

CDR0000069479

Identifier Type: -

Identifier Source: secondary_id

MSKCC-02024

Identifier Type: -

Identifier Source: secondary_id

U01CA069856

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-01410

Identifier Type: -

Identifier Source: org_study_id