A Phase I Trial of 5-Fluorouracil Given With 776C85 (GW776) and Low-Dose Leucovorin in Adult Patients With Solid Tumors

NCT00001579 | Completed Phase 1

• 2 other identifiers: 97013697-C-0136
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This is a dose escalation study. During the first period of this study, an initial pharmacological assessment of fluorouracil administered intravenously along with oral leucovorin calcium is made. Leucovorin calcium is given orally bid on days 1-3. Fluorouracil is given as a 24 hour infusion on day 2. After a 2 week rest period and resolution of any toxicities experienced during the first period of treatment, patients are given an escalating dose of fluorouracil with fixed doses of leucovorin calcium and ethynyluracil. Ethynyluracil and leucovorin calcium are given bid orally on days 1-3 of each week. Fluorouracil is given bid orally on day 2 of each week. Treatment is repeated for three weeks followed by a one week rest period. 3 to 6 patients are enrolled at each dose level. Dose escalation proceeds until the maximum tolerated dose (MTD) is determined. MTD is defined as the dose preceding that at which 2 or more patients experience dose limiting toxicity.

Conditions

Lymphoma; Neoplasms

Keywords

Biochemical Modulation; Dihydropyrimidine Dehydrogenase; Oral Administration; Pharmacokinetics

Interventions

5-Fluorouracil DRUG

Ethynyluracil DRUG

Leucovorin DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: Histologically proven solid tumor that has failed standard therapy or for which no such therapy exists. Tumor may be locally advanced and unresectable, recurrent and/or metastatic. Lymphomas with minimal or no involvement of bone marrow are also eligible. No primary malignancies or metastatic disease of the CNS. No symptomatic pre-existing peripheral neuropathy. PRIOR/CURRENT THERAPY: BIOLOGIC THERAPY: No immunotherapy within past 4 weeks. Recovered from toxic effects. CHEMOTHERAPY: No chemotherapy within past 4 weeks (6 weeks for nitrosoureas). No mitomycin within past 12 weeks. Recovered from toxic effects. ENDOCRINE THERAPY: Not specified. RADIOTHERAPY: No radiotherapy within past 2 weeks (8 weeks for strontium therapy). Recovered from toxic effects. SURGERY: Recovered from prior surgery. OTHER: No concurrent cimetidine. PATIENT CHARACTERISTICS: AGE: 18 and over. PERFORMANCE STATUS: ECOG 0-2. LIFE EXPECTANCY: Not specified. HEMATOPOIETIC: Absolute granulocyte count at least 2000/mm(3); Platelet count at least 100,000/mm(3). HEPATIC: Bilirubin no greater than 2 times upper normal limit; SGOT/SGPT no greater than 4 times upper normal limit. RENAL: Creatinine no greater than 1.6 mg/dL; Creatinine clearance greater than 55 mL/min. OTHER: Not pregnant or nursing. Fertile patients must use effective contraception. Not HIV positive. No active infections requiring intravenous antibiotic therapy. No other serious concurrent illness. No evidence of hemolytic uremic syndrome.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Cancer Institute (NCI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Evans RM, Laskin JD, Hakala MT. Assessment of growth-limiting events caused by 5-fluorouracil in mouse cells and in human cells. Cancer Res. 1980 Nov;40(11):4113-22. No abstract available.

  PMID: 6162543 BACKGROUND

• Spears CP, Shani J, Shahinian AH, Wolf W, Heidelberger C, Danenberg PV. Assay and time course of 5-fluorouracil incorporation into RNA of L1210/0 ascites cells in vivo. Mol Pharmacol. 1985 Feb;27(2):302-7.

  PMID: 2578605 BACKGROUND

• Calabro-Jones PM, Byfield JE, Ward JF, Sharp TR. Time-dose relationships for 5-fluorouracil cytotoxicity against human epithelial cancer cells in vitro. Cancer Res. 1982 Nov;42(11):4413-20. No abstract available.

  PMID: 7127282 BACKGROUND

MeSH Terms

Conditions

Lymphoma; Neoplasms

Interventions

Fluorouracil; eniluracil; Leucovorin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: December 10, 2002
• Study Start: June 1, 1997
• Study Completion: March 1, 2001
• Last Updated: July 17, 2006

Record last verified: 2000-05

Locations

US (1)