Sorafenib Plus S-1 in Advanced Solid Tumors

Sponsor

National Health Research Institutes, Taiwan (Other)

Overall Status

Completed

CT.gov ID

NCT01128998

Collaborator

National Cheng-Kung University Hospital (Other)

Enrollment

Location

Arm

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary Objective:

To define the recommended dose for phase II study of S-1 combined with sorafenib
To evaluate the dose-limiting toxicities of the combination therapy

Secondary Objectives:

To characterize the pharmacokinetics (PK) of sorafenib and S-1 in the combination therapy
To investigate the impact of genetic polymorphisms of metabolic genes on the PK of sorafenib and S-1, respectively, as well as on the toxicity profile of the combination.
To determine the changes of biomarkers between pre- and post-treatments.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Drug: Sorafenib Drug: S-1	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-Label Phase I Dose-Escalation Study of Sorafenib Plus S-1 in Advanced Solid Tumors

Study Start Date :

Nov 1, 2009

Actual Primary Completion Date :

Nov 1, 2009

Actual Study Completion Date :

Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: S-1 and Sorafenib	Drug: Sorafenib Name: Sorafenib Dosage form: 200 mg / Tablet Dosing schedule: 200 mg bid, po, everyday, since Day 8 of Cycle 1 Other Names: Nexavar Drug: S-1 Name:S-1 Dosage form: 20 mg or 25 mg / Capsule Dosing schedule: 20-40 mg/m2 bid,po, 14 days on & 7 days off Other Names: TS-1

Arm

Intervention/Treatment

Experimental: S-1 and Sorafenib

Drug: Sorafenib

Name: Sorafenib Dosage form: 200 mg / Tablet Dosing schedule: 200 mg bid, po, everyday, since Day 8 of Cycle 1

Other Names:

Nexavar

Drug: S-1

Name:S-1 Dosage form: 20 mg or 25 mg / Capsule Dosing schedule: 20-40 mg/m2 bid,po, 14 days on & 7 days off

Other Names:

TS-1

Outcome Measures

Primary Outcome Measures

Determination of MTD/RD [First two cycles]

Secondary Outcome Measures

Dose-limiting Toxicity [First two cycles]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically proven metastatic or locally advanced malignant solid tumors, which are refractory to current standard systemic treatment.
Have measurable lesion.
20-75 y/o.
ECOG performance score no more than 2.
Life expectancy > 12 weeks.
Adequate hematopoietic, hepatic and renal functions.

Hemoglobin > 9.0 g/dl
Absolute neutrophil count > 1,500/mm3
Platelet count 100,000/ mm3
Total bilirubin < 1.5 times the upper limit of normal (ULN)
ALT and AST < 2.5 x ULN
Serum creatinine < 1.0 x ULN

Recovery from prior therapy that given > 4 weeks before enrolment.
No pregnancy and breast-feeding.
Signed informed consent.

Exclusion Criteria:

Severe cardiovascular disorders.
Pulmonary fibrosis or interstitial pneumonia.
HIV infection.
Active infection.
Major anti-cancer treatment within 4 weeks of study entry.
Exposure to the current investigational agent before.
Known or suspected allergy to the current investigational agent.
Unable to swallow oral medications.
Substance abuse, medical, psychological or social conditions interfering with the patient's participation or evaluation of the study results.
Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study.
Symptoms of bowel obstruction, malnutrition, splenomegaly.
Receiving active anti-coagulant therapy.
Patients with concurrent CYP 2A6 and/or CYP 3A4 or 3A5 inducers or inhibitors; a minimal of 2 weeks wash-out period required.