Combination Chemotherapy in Treating Patients With Recurrent, Refractory, or Metastatic Solid Tumors or Lymphomas

Sponsor

National Institutes of Health Clinical Center (CC) (NIH)

Overall Status

Completed

CT.gov ID

NCT00019513

Collaborator

National Cancer Institute (NCI) (NIH)

108

Enrollment

Location

Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 gemcitabine, fluorouracil, and leucovorin in treating patients with recurrent, refractory, or metastatic solid tumors or lymphomas.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Esophageal Cancer Extrahepatic Bile Duct Cancer Gallbladder Cancer Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Small Intestine Cancer Unspecified Adult Solid Tumor, Protocol Specific	Drug: fluorouracil Drug: gemcitabine hydrochloride Drug: leucovorin calcium	Phase 1

Detailed Description

OBJECTIVES:

Determine the clinical toxic effects associated with administering sequential gemcitabine followed by fluorouracil with leucovorin calcium in patients with refractory or recurrent or metastatic solid tumors or lymphomas.
Determine achieved steady-state plasma levels of gemcitabine and fluorouracil in these patients.
Determine any antitumor activity of this regimen in these patients.
Determine the pharmacodynamics of gemcitabine and fluorouracil in these patients.

OUTLINE: This is a dose-escalation study of fluorouracil and gemcitabine.

During the first course, patients receive gemcitabine IV over 30 minutes once weekly for 2 weeks followed by one week of rest. During subsequent courses, patients receive gemcitabine as above followed immediately by fluorouracil IV over 24 hours once weekly for 2 weeks. Patients also receive leucovorin calcium orally on days 1 and 8 and IV on days 2 and 9. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Sequential dose escalation of fluorouracil is followed by sequential dose escalation of gemcitabine. Cohorts of 3-6 patients receive escalating doses of fluorouracil and then gemcitabine until the maximum tolerated dose (MTD) of the combination is determined. The MTD is defined as the dose preceding that at which 2 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A maximum of 108 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

108 participants

Primary Purpose:

Treatment

Official Title:

A Phase I Study of Weekly Gemcitabine in Combination With Infusional 5-Fluorouracil and Oral Calcium Leucovorin in Adult Cancer Patients

Study Start Date :

Aug 1, 1998

Actual Study Completion Date :

Jun 1, 2004

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of cancer that has failed standard therapy or for which no such therapy exists, including, but not limited to:
Unresectable primary or recurrent solid tumors (e.g., colon, pancreatic, lung, esophageal, or cholangiocarcinoma)
Metastatic disease
Lymphoma with no prior high-dose chemotherapy requiring autologous or allogeneic stem cell rescue
No leukemias
No CNS metastases or primary CNS malignancies
No failure on prior gemcitabine therapy

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-2

Life expectancy:

Not specified

Hematopoietic:

Absolute granulocyte count at least 2,000/mm^3
Platelet count at least 100,000/mm^3

Hepatic:

Bilirubin no greater than 2.0 mg/dL
Transaminases less than 6 times upper limit of normal

Renal:

Creatinine no greater than 2.0 mg/dL

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No other serious concurrent medical illness that would preclude study
No active infections requiring IV antibiotics
HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

See Disease Characteristics
More than 4 weeks since prior immunotherapy and recovered

Chemotherapy:

See Disease Characteristics
More than 4 weeks since prior chemotherapy (at least 6 weeks for mitomycin or nitrosoureas) and recovered
At least 3 months since prior suramin
At least 5 weeks since prior eniluracil (8 weeks prior to start of fluorouracil) and recovered