A Phase 1, Open-Label, Randomized, Cross-Over, Pharmacokinetic Study Evaluating the Effect of S-1 on Advanced Solid Tumors

NCT00400023 | Completed Phase 1

• 1 other identifier: TPU-S1108
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

Brief Summary

This is a Phase 1, open-label, randomized, 2-sequence, cross-over, pharmacokinetic (PK) study evaluating the effect of the DPD inhibitory action of CDHP as an S-1 component compared with FT alone on the PK of 5-FU in patients with advanced solid tumors. The study will be conducted in 2 parts (Cross-Over Pharmacokinetic Phase and S-1 Extension Phase).

Conditions

Tumors

Keywords

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (4)

• Cross-Over Pharmacokinetic Phase: To compare plasma concentrations, investigate the plasma and urine pharmacokinetic profiles, and to evaluate the duration of DPD inhibition after the administration of S-1

  The Cross-Over Pharmacokinetic phase (Part 1) will last 11 days

• S-1 Extension Phase: Efficacy (antitumor response)

  Each cycle of the S-1 Extension Phase (Part 2) will be 21 days (14 days 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.

• S-1 Extension Phase: Safety (Adverse events, lab assessments)

  Each cycle of the S-1 Extension Phase (Part 2) will be 21 days (14 days 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.

• S-1 Extension Phase: Pharmacokinetic profiles of the components of S-1 and their metabolites, and duration of DPD inhibition after administration of multiple doses (end of Cycle 1)

  Each cycle of the S-1 Extension Phase (Part 2) will be 21 days (14 days 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.

Study Arms (2)

1

EXPERIMENTAL

During the Cross-Over Pharmacokinetic Phase, patients will be randomly assigned to receive one of the following treatment sequences: * Sequence A: Single dose of 50 mg S-1 (2 capsules of 25 mg) on Day 1 followed by a single dose of 800 mg FT (8 capsules of 100 mg) on Day 8 * Sequence B: Single dose of 800 mg FT on Day 1 followed by a single dose of 50 mg S-1 on Day 8

Drug: S-1

2

ACTIVE COMPARATOR

During the Cross-Over Pharmacokinetic Phase, patients will be randomly assigned to receive one of the following treatment sequences: * Sequence A: Single dose of 50 mg S-1 (2 capsules of 25 mg) on Day 1 followed by a single dose of 800 mg FT (8 capsules of 100 mg) on Day 8 * Sequence B: Single dose of 800 mg FT on Day 1 followed by a single dose of 50 mg S-1 on Day 8

Drug: FT

Interventions

S-1 DRUG

During the Cross-Over PK Phase, S-1 will be administered as a 50 mg oral fixed dose and FT will be administered as an 800 mg oral fixed dose. During the S-1 Extension Phase (Part 2), S-1 30 mg/m2 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.

1

FT DRUG

During the Cross-Over PK Phase, S-1 will be administered as a 50 mg oral fixed dose and FT will be administered as an 800 mg oral fixed dose.

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has histologically or cytologically proven advanced solid tumors for which no standard therapy exists.
• Has provided written informed consent.
• Is 18 years of age or older.
• Is able to take medications orally.
• Has Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 (Appendix A, Performance Status).
• Has adequate organ function as defined by the following criteria:
• Has 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.
• Has a total serum bilirubin ≤ 1.5 times ULN.
• Has an absolute granulocyte count ≥ 1,500/mm3 (ie, ≥ 1.5 x 109/L by International Units \[IU\]).
• Has a platelet count ≥ 100,000/mm3 (IU: ≥ 100 x 109/L).
• Has a hemoglobin value of ≥ 9.0 g/dL.
• Has a calculated creatinine clearance \> 60 mL/min (by Cockcroft-Gault formula.76 See Appendix E).
• Is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

You may not qualify if:

• Has had treatment with any of the following within the specified time frame prior to study drug administration:
• An investigational agent received either concurrently or within the last 30 days.
• Previous therapy for malignancy within 21 days, including any chemotherapy, immunotherapy, biologic or hormonal therapy (6 weeks for nitrosureas or mitomycin C).
• Previous radiotherapy within 14 days.
• Current enrollment in another clinical study with an investigational agent. Patients participating in surveys or observational studies are eligible to participate in this study.
• Has a serious illness or medical condition(s) including, but not limited to, the following:
• 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).
• 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.
• 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.
• Known brain metastasis.
• Known leptomeningeal metastasis.
• Manifest ascites.
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
• Is receiving a concomitant treatment with drugs interacting with S-1 or FT. The following drugs are prohibited because there may be an interaction with S-1 or FT:
• Sorivudine, uracil, dipyridamole, cimetidine and folinic acid (may enhance S-1 or FT activity).

Sponsors & Collaborators

• Taiho Oncology, Inc.: lead

Study Sites (3)

Premiere Oncology of Arizona

Scottsdale, Arizona, 85260, United States

Location

Premiere Oncology, A Medical Corporation

Santa Monica, California, 90404, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

S 1 (combination)

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: November 14, 2006
• First Posted: November 16, 2006
• Study Start: September 1, 2006
• Primary Completion: May 1, 2007
• Study Completion: May 1, 2007
• Last Updated: September 3, 2024

Record last verified: 2024-08

Locations

US (3)