Escalation Study to Determine Bioavailability of a Single Oral Dose of Decitabine in Patients With Myelodysplastic Syndrome (MDS) - Full Text View

Sponsor:	Eisai Inc.
Information provided by:	Eisai Inc.
ClinicalTrials.gov Identifier:	NCT00941109

Purpose

The purpose of this study is to determine how the body absorbs decitabine when taken orally in patients with Myelodysplastic Syndrome (MDS). Safety will also be assessed for this oral dose.

Condition	Intervention	Phase
Myelodysplastic Syndrome	Drug: decitabine	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety Study
Official Title:	A Dose Escalation Study to Determine the Absolute Bioavailability of a Single Oral Dose Administration of Decitabine in Patients With Myelodysplastic Syndrome (MDS)

Resource links provided by NLM:

Drug Information available for: 5-Aza-2'-deoxycytidine

U.S. FDA Resources

Further study details as provided by Eisai Inc.:

Primary Outcome Measures:

Pharmacokinetic (PK) endpoints will be decitabine PK parameters: Tmax, Cmax, AUC0-inf, t1/2 and F. [ Time Frame: Cycle 1 on Days 1 & 2 from predose up to 6 hours after administration. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety evaluations will include assessments of adverse events (AEs), medical history, physical examinations, vital signs measurements, use of concomitant medications, and laboratory assessments at baseline and throughout the study period. [ Time Frame: Up to 30 days after the last dose of decitabine. ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	30
Study Start Date:	September 2009
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: decitabine Cohort 1: 30 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.
2: Experimental	Drug: decitabine Cohort 2: 60 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.
3: Experimental	Drug: decitabine Cohort 3: 120 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.
4: Experimental	Drug: decitabine Cohort 4: 180 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.
5: Experimental	Drug: decitabine Cohort 5: 240 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.

Detailed Description:

Cohorts are dosed sequentially, and escalation may stop before the 5th cohort is dosed. Each cycle will be approximately 4 weeks in length. Following Cycle 1, patients may receive an additional 4 follow-up cycles of decitabine. Cycles 2-5 will include a 20 mg/m^2 1-hour IV infusion of decitabine on Days 1-5 for all cohorts.

Eligibility

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

Criteria

Inclusion Criteria:

Histologically confirmed de novo or secondary MDS.
Age ≥ 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Adequate renal and hepatic function (creatinine ≤ 2.0 mg/dL, total bilirubin < 2.0 mg/dL, aspartate aminotransferase [AST] or alanine aminotransferase [ALT] < 3 times the upper limit of normal).
Life expectancy of at least 6 weeks.
If currently receiving 5 day decitabine regimen, patient must be scheduled to receive one more cycle of 5 day decitabine.
Recovered from all toxic effects of all prior therapy before entry into this study.
Women of childbearing potential and all men must agree to practice a medically approved form of contraception (one of the following must be used: condoms [male or female] with a spermicidal agent, diaphragm or cervical cap with a spermicidal agent, intrauterine device, hormonal contraception, abstinence) during the course of the study and up to 2 months following the last dose of decitabine.

Exclusion Criteria:

Candidates for up front high dose induction chemotherapy. MDS patients who are scheduled to receive decitabine prior to a bone marrow transplant or stem cell transplant are allowed.
History of treatment failure with decitabine.
Received any experimental agent within the preceding 30 days prior to screening.
Uncontrolled cardiac or pulmonary disease.
History of intestinal surgery, pancreatic surgery, or gastric surgery.
Any clinically relevant disease, disorder (including psychiatric disorders), or condition, in the opinion of the Investigator, which may interfere with the objectives of the study, especially with the gastrointestinal (GI) absorption of the study drug, and/or with the safety of the subject in the study.
Current active colitis of any etiology (Clostridium difficile colitis, ulcerative colitis, Crohn's disease, etc.) or a recent (< 2 weeks) episode of colitis.
Pregnant or lactating. Female patients of childbearing potential must have had a negative serum pregnancy test at screening and a negative urine pregnancy test on Day 1 prior to dosing.
Known positive serology for human immunodeficiency virus (HIV).
Active viral, fungal, or bacterial infection. No patient may enter the study unless infections have been fully treated.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00941109

Contacts

Contact: Eisai Call Center Eisai Call Center

888.422.4743

Locations

United States, Colorado

Denver, Colorado, United States
United States, New York

Bronx, New York, United States
United States, Texas

Houston, Texas, United States

Sponsors and Collaborators

Eisai Inc.

Investigators

Study Director:

Jim Ferry

Eisai Inc.

More Information

No publications provided

Responsible Party:	Eisai Medical Research ( Jim Ferry / VP Global Head ClinPhm&Translational Medicine )
Study ID Numbers:	E7373-A001-101
Study First Received:	July 15, 2009
Last Updated:	September 3, 2009
ClinicalTrials.gov Identifier:	NCT00941109 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Eisai Inc.:

MDS

Additional relevant MeSH terms:

Antimetabolites
Disease
Antimetabolites, Antineoplastic
Precancerous Conditions
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Hematologic Diseases
Myelodysplastic Syndromes
Enzyme Inhibitors

Decitabine
Pharmacologic Actions
Preleukemia
Neoplasms
Pathologic Processes
Therapeutic Uses
Syndrome
Bone Marrow Diseases

ClinicalTrials.gov processed this record on February 08, 2010