Advanced Solid Tumors
Conditions
Keywords
Sorafenib, S1, Advanced Solid Tumors, RD, MTD, DLT, PK, PG, Biomarker
Brief summary
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.
Interventions
DRUGS-1
1. Name:S-1 2. Dosage form: 20 mg or 25 mg / Capsule 3. Dosing schedule: 20-40 mg/m2 bid,po, 14 days on & 7 days off
DRUGSorafenib
1. Name: Sorafenib 2. Dosage form: 200 mg / Tablet 3. Dosing schedule: 200 mg bid, po, everyday, since Day 8 of Cycle 1
Sponsors
National Cheng-Kung University Hospital
National Health Research Institutes, Taiwan
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Determination of MTD/RD | First two cycles |
Secondary
| Measure | Time frame |
|---|---|
| Dose-limiting Toxicity | First two cycles |
Countries
Taiwan
Outcome results
None listed