Study Of Sunitinib With S-1 And Cisplatin For Gastric Cancer

Study Overview
=================
Brief Summary
-----------------
To assess the maximal tolerated dose (MTD) and overall safety of sunitinib when administered in combination with S-1 and Cisplatin in patients with advanced/metastatic gastric cancer.

Official Title
-----------------
A Phase 1 Study Of Sunitinib In Combination With S-1 And Cisplatin In Patients With Advanced Or Metastatic Gastric Cancer

Conditions
-----------------
Stomach Neoplasms

Intervention / Treatment
-----------------
* Drug: Cisplatin
* Drug: S-1
* Drug: Sunitinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed diagnosis of gastric cancer Chemonaive patients Adequate organ function Exclusion Criteria: Patients who meet the contra-indications of S-1 and Cisplatin. Prior chemotherapy failure patients

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: Cisplatin<br>* Cisplatin 60 mg/m2 on day 1 of each 28 day cycle<br>Drug: S-1<br>* S-1 80 mg/m2 on days 1-21 of each 28 day cycle<br>Drug: Sunitinib<br>* Sunitinib 25 mg, 37.5 mg and 50 mg daily S-1 80 mg/m2 on days 1-21 of each 28 day cycle Cisplatin 60 mg/m2 on day 1 of each 28 day cycle<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With First Cycle Dose-limiting Toxicities (DLTs) | A DLT is any of a predefined set of unacceptable adverse events, regardless of cause. DLTs were assessed during the first cycle (4 weeks). | Cycle 1 (Baseline to Week 4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) |  | Day 1 of Cycles 1 and 2 (pre-dose, 2, 4, 6, 8, 10, and 24 hours post-dose) | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) |  | Day 1 of Cycles 1 and 2 (pre-dose, 2, 4, 6, 8, 10, and 24 hours post-dose) | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | Day 1 of Cycles 1 and 2 (pre-dose, 2, 4, 6, 8, 10, and 24 hours post-dose) | 
| Maximum Observed Plasma Concentration (Cmax) of Tegafur and 5-FU |  | Day 1 of Cycles 1 and 2 (pre-dose, 1, 2, 4, 6, 8, and 10 hours post-dose) | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tegafur and 5-FU |  | Day 1 of Cycles 1 and 2 (pre-dose, 1, 2, 4, 6, 8, and 10 hours post-dose) | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Tegafur and 5-FU | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | Day 1 of Cycles 1 and 2 (pre-dose, 1, 2, 4, 6, 8, and 10 hours post-dose) | 
| Maximum Observed Plasma Concentration (Cmax) of Total Platinum and Free Platinum |  | Day 1 of Cycles 1 and 2 (pre-dose, 0.5, 1, 2, 8, and 22 hours after completing infusion) | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Total Platinum and Free Platinum |  | Day 1 of Cycles 1 and 2 (pre-dose, 0.5, 1, 2, 8, and 22 hours after completing infusion) | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Total Platinum and Free Platinum | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | Day 1 of Cycles 1 and 2 (pre-dose, 0.5, 1, 2, 8, and 22 hours after completing infusion) | 
| Number of Participants With Objective Response | Number of participants with objective response-based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR defined as the disappearance of all target lesions. PR defined as greater than or equal to (≥) 30 percent (%) decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Confirmed responses are those that persist on repeat imaging at least 4 weeks after initial documentation of response. | Baseline up to 739 days | 
| Number of Participants With Clinical Benefit Response (CBR) | CBR is defined as a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) for at least 24 weeks on study according to RECIST. Confirmed responses are those that persist on repeat imaging at least 4 weeks after initial documentation of response. | Baseline up to 739 days | 
| Duration of Response (DR) | Time from the first objective documentation of tumor response (confirmed or partial response) to first documented objective tumor progression or death due to cancer. DR calculated as (the end date for DR minus first subsequent confirmed CR or PR plus 1 day). | Baseline up to 739 days | 
| Progression-Free Survival (PFS) | Median time from the enrollment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. PFS calculated as (first event date minus enrollment date plus 1 day) | Baseline up to 739 days | 
| Time to Progression (TTP) | Time in months from enrollment to first documentation of objective tumor progression. TTP was calculated as (first event date or last known progression-free date minus the date of enrollment plus 1 day). Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD] per RECIST). | Baseline up to 739 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
chemotherapy, combination