Evaluating Patients With Impaired Hepatic Function

Impaired Hepatic Function Clinical Trial

Official title:

A Phase I, Open-Label Study Evaluating The Pharmacokinetics of Components of S-1 Patients With Impaired Hepatic Function

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00398424
• Other study ID #: TPU-S1112
• Status: Completed
• Phase: Phase 1
• First received: November 8, 2006
• Last updated: August 6, 2009
• Start date: February 2006
• Est. completion date: March 2009

Study information

• Verified date: August 2009
• Source: Taiho Oncology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a Phase I, Open-Label study evaluating the PK of S-1 components and their metabolites in patients with advanced solid tumors and varying degrees of hepatic function defined by the NCI classification for hepatic impairment. Patients will be stratified into 4 Cohorts- Normal, Mild, Moderate or Severe.

Six patients will be enrolled inot each cohort and receive S-1.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: March 2009
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

A patient must meet all of the following inclusion criteria to be eligible for enrollment in this study:

1. Has histologically or cytologically proven advanced solid tumors for which no standard therapy exists.

2. Has provided written informed consent.

3. Is 18 years of age or older.

4. Is able to take medications orally.

5. Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to = 2 (Appendix A, ECOG Performance Status).

6. Has adequate organ function as defined by the following criteria:

1. Absolute granulocyte count = 1,500/mm3 (ie, = 1.5 x 109/L by International Units [IU]).

2. Has a platelet count = 100,000/mm3 (IU: = 100 x 109/L).

3. Has a hemoglobin value of = 9.0 g/dL.

4. Has a calculated creatinine clearance > 60 mL/min (by Cockcroft-Gault

7. Is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria

Exclude a patient from this study if he/she does not fulfill the inclusion criteria, or if any of the following conditions are observed:

1. Has had treatment with any of the following within the specified time frame prior to study drug administration:

1. Any investigational agent received either concurrently or within the last 30 days.

2. Previous therapy for malignancy within 21 days, including any chemotherapy, immunotherapy, biologic or hormonal therapy (6 weeks for nitrosoureas or mitomycin C).

3. Previous radiotherapy within 14 days.

4. Current enrollment in another clinical trial.

5. Required shunting or stenting of the liver within prior 28 days or planned during the first study treatment cycle.

2. Has a serious illness or medical condition(s) including, but not limited to, the following:

1. Myocardial infarction within the last 6 months, severe/unstable angina, congestive heart failure (New York Heart Association [NYHA] Class III or IV, see Appendix F, NYHA Classification).

2. Known (at the time of entry) gastrointestinal disorder, including malabsorption,chronic nausea, vomiting, or diarrhea present to the extent that it might interfere with oral intake and absorption of the study medication.

3. Previous organ allograft, including liver transplantation.

4. Known brain metastasis.

5. Known leptomeningeal metastases.

6. Manifest ascites.

7. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.

8. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the patient inappropriate for entry into this study. • 3. Is receiving a concomitant treatment with drugs interacting with S-1. The following drugs are prohibited because there may be an interaction with S-1:

1. Sorivudine, uracil, dipyridamole, cimetidine and folinic acid (may enhance S-1 activity).

2. Allopurinol (may diminish S-1 activity).

3. Phenytoin (S-1 may enhance phenytoin activity).

4. Flucytosine, a fluorinated pyrimidine antifungal agent (may enhance S-1 and flucytosine activity).

5. Pilocarpine (may inhibit CYP2A6 activity).

4. Has known sensitivity to 5-FU. 5. Is a pregnant or lactating female. 6. Is a patient with reproductive potential who refuses to use an adequate means of contraception (including male patients).

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Impaired Hepatic Function

Intervention

Drug:
• S-1/Cisplatin
PK Phase (Part 1), Beginning on Day 1 of the Pharmacokinetic Phase, 30 mg/m2 S-1 will be administered orally BID for 14 days (Days 1 through 14), followed by a 1-week recovery period. On Day -2 and Day 14 of the Pharmacokinetic Phase, all patients will receive a single dose of 30 mg/m2 S-1 administered orally. Extension Phase, Patients will receive S-1 at the dose that they tolerated in the PK Phase. S-1 will be administered orally BID for 2 weeks (Day 1 through Day 14) followed by a 1-week recovery period (Day 15 through Day 21). This cycle will be repeated every 3 weeks.

Locations

Country	Name	City	State
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	University of Kentucky/Division of Hematology/Oncology and Blood Marrow Transplantation	Lexington	Kentucky
United States	Yale Cancer Center	New Haven	Connecticut
United States	The Institute for Drug Development	San Antonio	Texas
United States	Premiere Oncology of Arizona	Scottsdale	Arizona
United States	Washington University School of Medicine	St Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Taiho Oncology, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To provide specific dosing recommendations for S-1 in patients with hepatic impairment based on the PK of S-1 and its components after single dose and during steady state condition		The Pharmacokinetic Phase (Part 1) of the study will last 24 days.	No
Secondary	To assess the antitumor activity and safety profile of S-1 in patients with impaired hepatic function		Each cycle of the Extension Phase (Part 2) will be 21 days (14 days of S-1 treatment, 7 days recovery). The end of study for the Extension Phase will be 30 days after the last dose of S-1.	Yes