Study Of Sunitinib In Combination With Cisplatin And 5-Fluorouracil In Patients With Advanced Gastric Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine the safe and tolerable dose of sunitinib when given together with cisplatin and 5-fluorouracil in patients with advanced gastric cancer who have not received prior chemotherapy for their advanced cancer.

Official Title
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A Phase I Study Of Sunitinib Malate In Combination With Cisplatin And 5-Fluorouracil In Patients With Advanced Gastric Cancer

Conditions
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Stomach Neoplasms

Intervention / Treatment
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* Drug: 5-fluorouracil
* Drug: cisplatin
* Drug: sunitinib malate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: confirmed diagnosis of stomach cancer advanced stomach cancer stage IV adequate blood chemistry, blood counts and kidney function willing to participate to study requirements and to sign an informed consent document Exclusion Criteria: prior chemotherapy for stomach cancer in its advanced stage excessive toxicities related to prior therapies pregnant or breastfeeding patients

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: 5-fluorouracil<br>* 5- fluorouracil is given as 4000 mg/m^2 total dose over 96 hr continuous infusion of a 21 day chemotherapy cycle. Each 21 day cycle is repeated until progression of disease or unacceptable toxicity is observed.<br>Drug: cisplatin<br>* Cisplatin is given 80 mg/m^2 through a vein on day 1 every 21 days. Each 21 day cycle is repeated until progression of disease or unacceptable toxicity is observed.<br>Drug: sunitinib malate<br>* sunitinib is given orally 37.5mg /day for 14 days followed by 7 days of drug free period. Each 21 day cycle is repeated until progression of disease or unacceptable toxicity is observed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With First-cycle Dose Limiting Toxicities (DLTs) | The incidence of DLTs assessed during the first cycle (21 days). | Cycle 1 (Baseline to Day 21) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) |  | Day 1 of Cycle 1 (2, 4, 6, 8, 10, and 24 hours post dose) | 
| Area Under the Curve From Time 0 to 24 Hours Postdose [AUC (0-24)] | Area under the plasma concentration versus time curve from time 0 (pre-dose) to 24 hours postdose (0-24). | Day 1 of Cycle 1 (2, 4, 6, 8, 10, and 24 hours postdose) | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Tmax is the time to first occurrence of maximum observed plasma concentration (Cmax). | Day 1 of Cycle 1 (2, 4, 6, 8, 10, and 24 hours post dose) | 
| Steady State Concentration (Css) of 5-Fluorouracil (5-FU) | Steady state plasma concentration of 5-FU equals AUC(2-6) divided by 4, where AUC(2-6) is the area under the plasma concentration versus time curve from time 2 to 6 hours postdose (2-6). | Day 1 of Cycle 1 (2, 4, and 6 hours post infusion) | 
| Infusion Rate (Zero Order) (R0) of 5-FU | Infusion rate of 5-FU equals total dose divided by infusion time. | Day 1 of Cycle 1 (2, 4, and 6 hours post infusion) | 
| Clearance (CLss) of 5-FU | Steady state total body clearance equals infusion rate (zero order) divided by steady state plasma concentration of 5-FU (R0/Css). | Day 1 of Cycle 1 (2, 4, and 6 hours post infusion) | 
| Area Under the Curve From Time 2 to 6 Hours Postdose [AUC (2-6)] of 5-FU | Area under the plasma concentration versus time curve from time 2 to 6 hours postdose (2-6). | Day 1 of Cycle 1 (2, 4, and 6 hours post infusion) | 
| Number of Participants With Objective Response | Number of participants with an 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. | Baseline, Day 21 of every even-numbered cycle up to 15 Months | 
| 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 any cause, whichever occurrs first. DR calculated as (Months) equals (the end date for DR minus first subsequent confirmed CR or PR plus 1) divided by 30. | Baseline up to Month 15 | 
| Progression-Free Survival (PFS) | Median time (50%) from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. PFS calculated as (Months) equals (first event date minus first dose date plus 1) divided by 30. | Baseline up to Month 15 |