Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

5-Fluoro-2'-Deoxycytidine and Tetrahydrouridine in Treating Patients With Advanced Solid Tumors

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Diagnostic, Treatment Active 18 and over NCI NCI-06-C-0221 NCI-P7001, CCC-PHI-16, NCT00378807

Special Category: NIH Clinical Center trial, NIH Clinical Center trial

Objectives

1. Determine the maximum tolerated dose of 5-fluoro-2'-deoxycytidine when given together with tetrahydrouridine in patients with advanced solid tumors.
2. Determine the toxicity of this regimen in these patients.
3. Assess the pharmacokinetics of this regimen in these patients.
4. Determine the relative levels of mRNAs for thymidylate synthase, deoxycytidine kinase, dCMP deaminase, and other relevant enzymes in patients treated with this regimen.
5. Determine the methylation status of p16 and other genes relevant to neoplasias.

Entry Criteria

Disease Characteristics:

• Histologically confirmed advanced solid tumor
  • Breast cancer patients have a higher priority for accrual



• Disease must be refractory to standard therapy OR no standard therapy exists



• Measurable disease allowed, but not required
  • If bidimensionally measurable disease is present, baseline measurements of ≤ 3 indicator lesions must be available within the past 4 weeks
  • No pleural effusions, ascites, or bone metastases as measurable disease



• Hormone receptor status not specified

Prior/Concurrent Therapy:

• Recovered from all prior therapy
• Recovered from prior major surgery
• At least 4 weeks since prior and no other concurrent antineoplastic therapies
• No concurrent treatment for severe infection
• No other concurrent investigational therapy

Patient Characteristics:

• Karnofsky performance status 60-100%
• Male or female
• Menopausal status not specified
• Life expectancy ≥ 2 months
• Creatinine ≤ 2.0 mg/dL
• Creatinine clearance ≥ 50 mL/min
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 125,000/mm³
• Bilirubin ≤ 1.5 mg/dL
• SGOT and SGPT ≤ 3 times upper limit of normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No concurrent severe poorly controlled nonmalignant illness (e.g., cardiovascular, pulmonary, or central nervous system disease)

Expected Enrollment

A total of 80 patients will be accrued for this study.

Outcomes

Maximum tolerated dose of 5-fluoro-2'-deoxycytidine (5FD) given together with tetrahydrouridine (THU)
Toxicity of 5FD and THU
Pharmacokinetic profile of 5FD and THU
Relative levels of mRNAs for thymidylate synthase, deoxycytidine kinase, dCMP deaminase, and other relevant enzymes
Methylation status of p16 and other genes relevant to neoplasias

Outline

This is a multicenter, dose-escalation study of 5-fluoro-2'-deoxycytidine (5FD).

Patients receive tetrahydrouridine (THU) IV over 3 hours and 5FD IV over 3 hours on days 1-5 and 8-12. Treatment repeats every 28 days in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of 5FD until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Blood and biopsy samples are collected before course 1 and on the last day of study treatment for pharmacodynamic studies. During course 1, plasma is collected on days 1, 3, and 5 and urine is collected on days 1 and 3 for pharmacokinetic studies.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research-Medical Oncology

James Doroshow, MD, Principal investigator		Ph: 301-496-4291 Email: doroshoj@mail.nih.gov

U.S.A.
California
	Duarte
	City of Hope Comprehensive Cancer Center
		Clinical Trials Office - City of Hope Comprehensive Cancer Center	Ph:  800-826-4673
			Email: becomingapatient@coh.org
	Los Angeles
	USC/Norris Comprehensive Cancer Center and Hospital
		Clinical Trials Office - USC/Norris Comprehensive Cancer Center and Hospital	Ph:  323-865-0451
	Sacramento
	University of California Davis Cancer Center
		Clinical Trials Office - University of California Davis Cancer Center	Ph:  916-734-3089
Maryland
	Bethesda
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
		Clinical Trials Office - Warren Grant Magnusen Clinical Center - NCI Clinical Trials Referral Office	Ph:  888-NCI-1937

Related Information

Featured trial article
Web site for additional information

Registry Information
Official Title		A Phase I Trial of 5-Fluoro-2'-Deoxycytidine with Tetrahydrouridine in Advanced Malignancies
Trial Start Date		1999-01-26
Registered in ClinicalTrials.gov		NCT00378807
Date Submitted to PDQ		2006-08-09
Information Last Verified		2008-04-04