Sorafenib Plus S-1 in Advanced Solid Tumors

Study Overview
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Brief Summary
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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.

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

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: Sorafenib
* Drug: S-1


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: S-1 and Sorafenib<br> | Drug: Sorafenib<br>* Name: Sorafenib Dosage form: 200 mg / Tablet Dosing schedule: 200 mg bid, po, everyday, since Day 8 of Cycle 1<br>* Other names: Nexavar;Drug: S-1<br>* 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<br>* Other names: TS-1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of MTD/RD |  | First two cycles | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting Toxicity |  | First two cycles | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sorafenib, S1, Advanced Solid Tumors, RD, MTD, DLT, PK, PG, Biomarker