Irinotecan Followed by Fluorouracil in Treating Patients With Advanced Solid Tumors

Roswell Park Comprehensive Cancer Center

Status and phase: Completed; Phase 1

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Treatments: Drug: irinotecan hydrochloride; Drug: fluorouracil

Study type: Interventional

Funder types: Other

Identifiers

NCT00024141

CDR0000068895

RPCI-RP-01-01

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of irinotecan followed by fluorouracil in treating patients who have advanced solid tumors.

Full description

OBJECTIVES:

• Determine the optimal dose of irinotecan when administered before fluorouracil in patients with advanced solid tumors.
• Determine the toxic effects of this regimen in these patients.
• Correlate the pharmacokinetics of irinotecan with its biologic effects in these patients.
• Assess, in a preliminary manner, the antitumor activity of this regimen in these patients.

OUTLINE: This is a dose de-escalation study of irinotecan.

Patients receive irinotecan IV over 90 minutes on days 1, 8, 15, and 22 and fluorouracil IV over 5 minutes on days 2, 9, 16, and 23. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 6 patients receive decreasing doses of irinotecan until the optimal dose is determined. The optimal dose is defined as the dose at which at least 3 of 6 patients show evidence of recruitment of cells into the S phase at 24 hours after irinotecan administration.

PROJECTED ACCRUAL: A total of 18-24 patients will be accrued for this study within 12-18 months.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically proven recurrent or metastatic solid tumor that is not amenable to curative surgery, radiotherapy, or conventional chemotherapy of proven value
• Must have disease that can be safely and readily biopsied under local anesthesia (including, but not limited to, subcutaneous metastases, superficial lymph node metastases, or ascites)

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• WBC at least 4,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST less than 2 times ULN
• Alkaline phosphatase less than 2 times ULN
• Lactic dehydrogenase less than 2 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN

Other:

• HIV negative
• No active uncontrolled bacterial, viral, or fungal infection
• No nonmalignant systemic disease that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• No prior irinotecan

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy except small-port radiotherapy for local control
• No concurrent radiotherapy except small-port radiotherapy for local disease control (e.g., pain relief or impending fracture)

Surgery:

• See Disease Characteristics
• At least 2 weeks since prior major surgery

Other:

• No concurrent anticoagulants except warfarin or subcutaneous heparin