5-Fluoro-2'-Deoxcyctidine and Tetrahydrouridine to Treat Patients With Advanced Cancer
NCT ID: NCT00359606
Last Updated: 2015-05-06
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
58 participants
INTERVENTIONAL
1999-04-30
2012-06-30
Brief Summary
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Detailed Description
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I. To determine the maximum tolerated dose (MTD) of 5-fluoro-2'-deoxycytidine (5-fluoro-2-deoxycytidine) (FdCyd) administered by intravenous (IV) infusion over three hours with concomitant infusion of 350 mg/m2 of tetrahydrouridine (THU).
II. To describe the toxicities of FdCyd co-infused with THU.
III. To obtain preliminary evidence of anti-tumor activity in patients treated with this combination.
IV. To evaluate the pharmacokinetics of FdCyd and THU when co-infused.
V. To evaluate the oral bioavailability of FdCyd when co-administered with THU.
VI. When feasible, to measure the relative levels of the messenger ribonucleic acid (mRNA)'s for thymidylate synthase, deoxycytidine kinase, deoxycytidylate (dCMP) deaminase and other relevant enzymes; and the methylation status of p16 and other genes relevant to neoplasia.
OUTLINE: This is a dose-escalation study of 5-fluoro-2-deoxycytidine. Patients receive tetrahydrouridine orally (PO) on day 1; 5-fluoro-2-deoxycytidine PO on days 1 and 8; tetrahydrouridine IV over 3 hours on days 2-5, 8, and 9-12; and 5-fluoro-2-deoxycytidine IV over 3 hours on days 2-5 and 9-12 of course 1. For all subsequent courses, patients receive tetrahydrouridine IV over 3 hours and 5-fluoro-2-deoxycytidine IV over 3 hours on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment (5-fluoro-2-deoxycytidine, tetrahydrouridine)
Patients receive tetrahydrouridine PO on day 1; 5-fluoro-2-deoxycytidine PO on days 1 and 8; tetrahydrouridine IV over 3 hours on days 2-5, 8, and 9-12; and 5-fluoro-2-deoxycytidine IV over 3 hours on days 2-5 and 9-12 of course 1. For all subsequent courses, patients receive tetrahydrouridine IV over 3 hours and 5-fluoro-2-deoxycytidine IV over 3 hours on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
5-Fluoro-2-Deoxycytidine (FdCyd)
Given PO and IV
Laboratory Biomarker Analysis
Correlative Studies
Pharmacological Study
Correlative Studies
Tetrahydrouridine (THU)
Given PO and IV
Interventions
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5-Fluoro-2-Deoxycytidine (FdCyd)
Given PO and IV
Laboratory Biomarker Analysis
Correlative Studies
Pharmacological Study
Correlative Studies
Tetrahydrouridine (THU)
Given PO and IV
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Karnofsky performance status of at least 60% and estimated survival of at least two months
* Serum creatinine =\< 2.0 mg/dl or creatinine clearance \>= 50 ml/min
* Absolute neutrophil count (ANC) \>= 1,500/ul
* Platelets \>= 125,000/ul
* Bilirubin =\< 1.5 mg/dl
* Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =\< 3 times the upper limits of normal
* Prior antineoplastic therapy must have been completed at least four weeks prior to the patient's entry on this study, or patients must have recovered from any expected side effects of the prior therapy; there is no limit on the number of cycles of prior chemotherapy
* Patients must be ineligible for or have refused participation in higher priority institutional protocols
* Written, voluntary, informed consent of the patient must be obtained in compliance with institutional, state and federal guidelines
* Pregnant patients are INELIGIBLE; all patients of child-bearing potential, both male and female, must be advised to practice adequate contraception; premenopausal women must have a negative pregnancy test prior to entry on this study
* Patients with any non-malignant intercurrent illness (e.g. cardiovascular, pulmonary, or central nervous system disease) which is either poorly controlled with currently available treatment, or which is of such severity that the investigators deem it inappropriate to treat the patient on this protocol are INELIGIBLE
* Patients currently being treated for a severe infection or who are recovering from major surgery are INELIGIBLE until recovery is deemed complete by the investigators
* The presence of measurable disease is NOT required for this phase I study; if bidimensionally measurable disease is present, baseline measurements of up to 3 indicator lesions should be made no earlier than four weeks prior to the first cycle of chemotherapy; pleural effusions, ascites and bone metastases are not considered measurable
* Complete blood count (CBC), differential count, platelet count, and blood chemistries should be done no earlier than 72 hours prior to each cycle of chemotherapy
* Pretreatment tests should be done no earlier than two weeks prior to the first cycle of chemotherapy
* Priority for accrual will be given to patients with breast cancer due to the in vitro data suggesting potential activity for this disease
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
City of Hope Medical Center
OTHER
Responsible Party
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Principal Investigators
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Robert Morgan, MD
Role: PRINCIPAL_INVESTIGATOR
City of Hope Medical Center
Locations
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City of Hope National Medical Center
Duarte, California, United States
USC/Norris Comprehensive Cancer Center
Los Angeles, California, United States
University of California, Davis Cancer Center
Sacramento, California, United States
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States
Countries
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References
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Carter SK. Editorial: Large-bowel cancer-The current status of treatment. J Natl Cancer Inst. 1976 Jan;56(1):3-10. doi: 10.1093/jnci/56.1.3. No abstract available.
Doroshow JH, Multhauf P, Leong L, Margolin K, Litchfield T, Akman S, Carr B, Bertrand M, Goldberg D, Blayney D, et al. Prospective randomized comparison of fluorouracil versus fluorouracil and high-dose continuous infusion leucovorin calcium for the treatment of advanced measurable colorectal cancer in patients previously unexposed to chemotherapy. J Clin Oncol. 1990 Mar;8(3):491-501. doi: 10.1200/JCO.1990.8.3.491.
Keyomarsi K, Moran RG. Folinic acid augmentation of the effects of fluoropyrimidines on murine and human leukemic cells. Cancer Res. 1986 Oct;46(10):5229-35.
Holleran JL, Beumer JH, McCormick DL, Johnson WD, Newman EM, Doroshow JH, Kummar S, Covey JM, Davis M, Eiseman JL. Oral and intravenous pharmacokinetics of 5-fluoro-2'-deoxycytidine and THU in cynomolgus monkeys and humans. Cancer Chemother Pharmacol. 2015 Oct;76(4):803-11. doi: 10.1007/s00280-015-2857-x. Epub 2015 Sep 1.
Related Links
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NIH Clinical Center Detailed Web Page
Other Identifiers
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PHI-16
Identifier Type: OTHER
Identifier Source: secondary_id
UM1CA62505
Identifier Type: OTHER_GRANT
Identifier Source: secondary_id
NCI-2015-00655
Identifier Type: REGISTRY
Identifier Source: secondary_id
06-C-0221
Identifier Type: OTHER
Identifier Source: secondary_id
98127
Identifier Type: -
Identifier Source: org_study_id
NCT00378807
Identifier Type: -
Identifier Source: nct_alias
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