Evaluating Patients With Varying Degrees of Renal Function

This study has been completed.
Sponsor:
Information provided by:
Taiho Pharma USA, Inc.
ClinicalTrials.gov Identifier:
NCT00398307
First received: November 8, 2006
Last updated: April 7, 2011
Last verified: April 2011
  Purpose

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 renal function. Patients will be stratified by baseline 24-hour creatinine clearance(CrCL) into 4 cohorts using the normal clearance formula:

Group A: Control Group B:Mild renal dysfunction Group C:Moderate renal function and Group D: Severe renal dysfunction. Six patients will be enrolled into each cohort.


Condition Intervention Phase
Renal Impairment
Drug: S-1/Cisplatin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label Study Evaluating the Pharmacokinetics of Components of S-1 in Patients With Varying Degrees of Renal Function

Resource links provided by NLM:


Further study details as provided by Taiho Pharma USA, Inc.:

Primary Outcome Measures:
  • To provide specific dosing recommendations for S-1 in patients with renal impairment based on the PK of S-1 and its components after single dose and steady state conditions. [ Time Frame: The Pharmacokinetic Phase (Part 1) of the study will last 24 days. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assess Anti-tumor activity, and safety profile of S-1 in patients with impaired renal function [ Time Frame: 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. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 24
Study Start Date: February 2006
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: S-1/Cisplatin

    S-1 administration will be determined by degree of renal impairment as follows:

    Group A (Control): 30 mg/m2 BID Group B (Mild renal dysfunction): 30 mg/m2 BID Group C (Moderate renal dysfunction): 20 mg/m2 BID Group D (Severe renal dysfunction): 20 mg/m2 QD

    Pharmacokinetic Phase (Part 1):

    On Days -2 and 14 of the Pharmacokinetic Phase, patients will receive a single dose of S-1 administered orally in the morning.

    Treatment will be followed by 1 week of recovery (Days 15 through 21).

    Extension Phase (Part 2):

    S-1 will be administered orally 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.

  Eligibility

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

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. Transaminases AST (SGOT) and ALT (SGPT) ≤ 2.5 times the upper limit of normal(ULN). If liver function abnormalities are due to underlying malignancy, then AST(SGOT) and ALT (SGPT) may be ≤ 5 times ULN.
      2. Total serum bilirubin ≤ 1.5 times ULN.
      3. Absolute granulocyte count ≥ 1,500/mm3 (ie, ≥ 1.5 x 109/L by International Units [IU]).
      4. Has a platelet count ≥ 100,000/mm3 (IU: ≥ 100 x 109/L).
      5. Has a hemoglobin value of ≥ 9.0 g/dL.
    7. Is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

3.3.2 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.
  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, Appendix E, 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. Known brain metastasis.
    4. Known leptomeningeal metastases.
    5. Requires hemodialysis.
    6. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome(AIDS)-related illness.
    7. 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00398307

Locations
United States, Arizona
Premiere Oncology of Arizona
Scottsdale, Arizona, United States, 85260
United States, California
LAC/USC Medical Center
Los Angeles, California, United States, 90033
Premiere Oncology
Santa Monica, California, United States, 90404
United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06520
United States, Kentucky
University of Kentucky/Division of Hematology/Oncology and Blood Marrow Transplantation
Lexington, Kentucky, United States, 40536
United States, Maryland
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, United States, 21201
United States, Missouri
Washington University School of Medicine
St Louis, Missouri, United States, 63110
United States, New Mexico
Cancer Research & Treatment Center/University of New Mexico
Albuquerque, New Mexico, United States, 87131
United States, Texas
The Institute for Drug Development
San Antonio, Texas, United States, 78245
Sponsors and Collaborators
Taiho Pharma USA, Inc.
  More Information

No publications provided

Responsible Party: Michele Houghton/Global Senior Director, Clinical Operations, Taiho Pharma USA, Inc.
ClinicalTrials.gov Identifier: NCT00398307     History of Changes
Other Study ID Numbers: TPU-S1111
Study First Received: November 8, 2006
Last Updated: April 7, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Taiho Pharma USA, Inc.:
Renal Impairment

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014