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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00019513
• Other study ID #: 980143
• Secondary ID: 98-C-0143CDR0000
• Status: Completed
• Phase: Phase 1
• First received: July 11, 2001
• Last updated: March 21, 2012
• Start date: August 1998
• Est. completion date: June 2004

Study information

• Verified date: March 2012
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00001706

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• Est. completion date: June 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endocrine therapy:

• No steroid therapy if utilized for chronic lymphoma therapy

• At least 4 weeks since prior steroidal therapy as disease treatment

Radiotherapy:

• At least 2 weeks since prior radiotherapy to no more than 20% of bone marrow

• At least 4 weeks since prior radiotherapy to 21% or more of bone marrow

• Recovered from prior radiotherapy

Surgery:

• Recovered from prior surgery

Other:

• No concurrent cimetidine

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bile Duct Neoplasms
• Cholangiocarcinoma
• Colorectal Cancer
• Esophageal Cancer
• Esophageal Neoplasms
• Extrahepatic Bile Duct Cancer
• Gallbladder Cancer
• Gallbladder Neoplasms
• Liver Cancer
• Liver Neoplasms
• Lung Cancer
• Lymphoma
• Pancreatic Cancer
• Pancreatic Neoplasms
• Small Intestine Cancer
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• fluorouracil

• gemcitabine hydrochloride

• leucovorin calcium

Locations

Country	Name	City	State
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
National Institutes of Health Clinical Center (CC)	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Wright MA, Schuler B, Szabo E, Grem JL. Sustained partial response of an intra-abdominal desmoid tumor treated with gemcitabine, 5-fluorouracil and leucovorin. Ann Oncol. 2003 Apr;14(4):659-60. — View Citation