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

Sponsored by:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00378807

Purpose

RATIONALE: Drugs used in chemotherapy, such as 5-fluoro-2'-deoxycytidine and tetrahydrouridine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of 5-fluoro-2'-deoxycytidine when given together with tetrahydrouridine in treating patients with advanced solid tumors.

Condition	Intervention	Phase
Breast Cancer Unspecified Adult Solid Tumor, Protocol Specific	Drug: 5-fluoro-2-deoxycytidine Drug: tetrahydrouridine Other: pharmacological study Procedure: biopsy	Phase I

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Tetrahydrouridine Deoxycytidine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Trial of 5-Fluoro-2'-Deoxycytidine With Tetrahydrouridine in Advanced Malignancies

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose of 5-fluoro-2'-deoxycytidine (5FD) given together with tetrahydrouridine (THU) [ Designated as safety issue: Yes ]
Toxicity of 5FD and THU [ Designated as safety issue: Yes ]
Pharmacokinetic profile of 5FD and THU [ Designated as safety issue: No ]
Oral bioavailability of 5FD and THU [ Designated as safety issue: No ]
Relative levels of mRNAs for thymidylate synthase, deoxycytidine kinase, dCMP deaminase, and other relevant enzymes [ Designated as safety issue: No ]
Methylation status of p16 and other genes relevant to neoplasias [ Designated as safety issue: No ]

Estimated Enrollment:	80
Study Start Date:	January 1999

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose of 5-fluoro-2'-deoxycytidine when given together with tetrahydrouridine in patients with advanced solid tumors.
Determine the toxicity of this regimen in these patients.
Assess the pharmacokinetics of this regimen in these patients.
Evalutate the oral bioavailability of this regimen in these patients.
Determine the relative levels of mRNAs for thymidylate synthase, deoxycytidine kinase, dCMP deaminase, and other relevant enzymes in patients treated with this regimen.
Determine the 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 a single dose of oral tetrahydrouridine (THU) and oral 5FD on day 1 followed by THU IV over 3 hours and 5FD IV over 3 hours on days 2-5 and 8-12 in course 1. Beginning in course 2 and all subsequent courses, patients receive 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 at baseline and periodically during study for pharmacodynamic studies. Plasma and urine samples are collected periodically during study for pharmacokinetic studies.

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

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)

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00378807

Locations

United States, California
City of Hope Comprehensive Cancer Center	Recruiting
Duarte, California, United States, 91010-3000
Contact: Clinical Trials Office - City of Hope Comprehensive Cancer Cen 800-826-4673 becomingapatient@coh.org
University of California Davis Cancer Center	Recruiting
Sacramento, California, United States, 95817
Contact: Clinical Trials Office - University of California Davis Cancer 916-734-3089
USC/Norris Comprehensive Cancer Center and Hospital	Recruiting
Los Angeles, California, United States, 90089-9181
Contact: Clinical Trials Office - USC/Norris Comprehensive Cancer Cente 323-865-0451
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center 888-NCI-1937

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Principal Investigator:

James H. Doroshow, MD

National Cancer Institute (NCI)

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Featured trial article This link exits the ClinicalTrials.gov site

Web site for additional information This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000502207, NCI-06-C-0221, NCI-P7001, CCC-PHI-16
Study First Received:	September 19, 2006
Last Updated:	March 31, 2009
ClinicalTrials.gov Identifier:	NCT00378807 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific
stage IIIA breast cancer
stage IIIB breast cancer

stage IIIC breast cancer
stage IV breast cancer
recurrent breast cancer

Study placed in the following topic categories:

Antimetabolites
Skin Diseases
Tetrahydrouridine

Breast Neoplasms
Breast Diseases
Recurrence

Additional relevant MeSH terms:

Antimetabolites
Neoplasms
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action
Skin Diseases

Tetrahydrouridine
Breast Neoplasms
Pharmacologic Actions
Breast Diseases

ClinicalTrials.gov processed this record on May 07, 2009