Irinotecan and Gemcitabine in Treating Patients With Refractory 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: gemcitabine hydrochloride

Study type

Interventional

Funder types

Other

Identifiers

NCT00054288

CDR0000270343

RPCI-DS-01-18

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. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining irinotecan with gemcitabine in treating patients who have refractory advanced solid tumors.

Full description

OBJECTIVES:

Determine the maximum tolerated dose of irinotecan when administered with gemcitabine in patients with refractory advanced solid tumors.
Determine the antitumor activity and toxicity of this regimen in these patients.
Determine the pharmacokinetics and pharmacodynamics of this regimen in these patients.
Determine the optimal dose and time interval for this regimen in these patients.

OUTLINE: This is an open-label, non-randomized, dose-escalation study of irinotecan.

Patients receive irinotecan IV over 90 minutes on days 1 and 8 and gemcitabine IV over 30 minutes on days 2 and 9. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 8 weeks.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study within 2 years.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed advanced solid tumor that is refractory to prior treatment
- Considered incurable with other modalities
Measurable or evaluable disease
- The following are not considered measurable or evaluable:
  - Bone metastases
  - Pleural, pericardial, or peritoneal effusions
  - Irradiated lesions (unless progression is documented after radiotherapy)
- Metastatic disease that has been followed using serum tumor markers allowed
No symptomatic brain metastases
Brain metastases may not be sole site of metastatic disease

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-1

Life expectancy

At least 12 weeks

Hematopoietic

WBC at least 3,000/mm^3
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3

Hepatic

AST and ALT no greater than 1.5 times normal
Bilirubin no greater than 1.5 mg/dL
No clinically apparent jaundice

Renal

Creatinine no greater than 1.6 mg/dL OR
Creatinine clearance at least 50 mL/min

Cardiovascular

Cardiac function normal
No uncontrolled heart disease
No myocardial infarction within the past 3 months
No congestive heart failure
No unstable or uncontrolled angina

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
No active infection requiring systemic therapy
No uncontrolled seizures
No uncontrolled diabetes mellitus

PRIOR CONCURRENT THERAPY:

Biologic therapy