Sorafenib Plus S-1 in Advanced Solid Tumors

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

Primary Objective:

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

Secondary Objectives:

1. To characterize the pharmacokinetics (PK) of sorafenib and S-1 in the combination therapy
2. 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.
3. To determine the changes of biomarkers between pre- and post-treatments.

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.

  1. Hemoglobin > 9.0 g/dl
  2. Absolute neutrophil count > 1,500/mm3
  3. Platelet count 100,000/ mm3
  4. Total bilirubin < 1.5 times the upper limit of normal (ULN)
  5. ALT and AST < 2.5 x ULN
  6. 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.