Clinical trial NCT01128998: Sorafenib Plus S-1 in Advanced Solid Tumors
Official title: An Open-Label Phase I Dose-Escalation Study of Sorafenib Plus S-1 in Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Sorafenib
S1
Advanced Solid Tumors
RD
MTD
DLT
PK
PG
Biomarker
Lead sponsor: National Health Research Institutes, Taiwan
Sponsor class: OTHER
Collaborators: name: National Cheng-Kung University Hospital
First posted: 2010-05-24
Enrollment: 30
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Determination of MTD/RD
timeFrame: First two cycles
Secondary outcomes:
measure: Dose-limiting Toxicity
timeFrame: First two cycles
Other outcomes:
Locations:
city: Tainan City
country: Taiwan
facility: National Cheng-Kung University Hospital
Study officials:
affiliation: National Institute of Cancer Research, National Health Research Institution, Taiwan
name: Li-Tzong Chen, M.D., Ph.D.
role: STUDY_CHAIR
References: