Study Of Sunitinib In Combination With Cisplatin/Capecitabine Or Oxaliplatin/Capecitabine In Patients With Advanced Gastric Cancer

Study Overview
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Brief Summary
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The purpose of the study is to determine the safe and tolerable doses of sunitinib given together with either cisplatin and capecitabine or oxaliplatin and capecitabine in patients who have advanced gastric cancer who have not received prior chemotherapy for their advanced cancer

Official Title
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A Phase 1 Study Of Sunitinib Malate In Combination With Cisplatin/Capecitabine Or Oxaliplatin/Capecitabine In Patients With Advanced Gastric Cancer

Conditions
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Stomach Neoplasms

Intervention / Treatment
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* Drug: capecitabine
* Drug: oxaliplatin
* Drug: sunitinib malate
* Drug: capecitabine
* 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 of stage IV adequate blood chemistry, blood counts and kidney function willing to participate to study requirements and sign an informed consent document Exclusion Criteria: prior chemotherapy for the 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: capecitabine<br>* Capecitabine is given orally at 1000mg/m^2 twice a day for 14 days followed by 7 days of drug free period.<br>Drug: oxaliplatin<br>* Oxaliplatin is given 110mg/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 25mg/day for 14 days followed by 7 days of drug free period.<br>* Other names: Sutent;|
| Experimental: B<br> | Drug: capecitabine<br>* Capecitabine is given orally at 1000mg/m^2 twice a day for 14 days followed by 7 days of drug free period.<br>Drug: cisplatin<br>* Cisplatin is given 80mg/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 25mg/day for 14 days followed by 7 days of drug free period.<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) | Any DLT event in Cycle 1: Grade (GR) 3/4 nausea, vomiting, or diarrhea despite anti-emetics, anti-diarrheals; GR 3 nonhematological toxicity for greater than or equal to (≥)7 days (except alopecia, skin or hair discoloration, hyperamylasemia, or hyperlipasemia without other clinical evidence of pancreatitis and asymptomatic hyperuricemia); GR 4 nonhematological toxicity; GR 4 neutropenia ≥7 days or thrombocytopenia; GR ≥3 febrile neutropenia or neutropenic infection; GR 3 thrombocytopenia ≥7 days; any treatment-related toxicity having >3 consecutive CAP or SU missed doses per cycle; delayed toxicity recovery >14 days. | Baseline up to Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of SU, SU012662 (Metabolite of SU), and Total Drug (SU + SU012662) |  | Day 14 of Cycle 1 (predose and 2, 4, 6, 8, 10, and 24 hours postdose) | 
| Cmax of CAP |  | Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) | 
| Cmax of 5'-Deoxy-5-fluorocytidine (Metabolite of CAP, 5'DFCR) |  | Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) | 
| Cmax of 5'-Deoxy-5-fluorouridine (Metabolite of CAP, 5'DFUR) |  | Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) | 
| Cmax of 5-fluorouracil (Metabolite of CAP, 5-FU) |  | Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) | 
| Minimum Observed Plasma Trough Concentration (Cmin) of SU, SU012662, and Total Drug (SU + SU012662) |  | Day 14 of Cycle 1 (predose and 2, 4, 6, 8, 10, and 24 hours postdose) | 
| Cmin of CAP |  | Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) | 
| Cmin of 5'DFCR |  | Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) | 
| Cmin of 5'DFUR |  | Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) | 
| Cmin of 5-FU |  | Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) for SU, SU012662, and Total Drug (SU + SU012662) |  | Day 14 of Cycle 1 (predose and 2, 4, 6, 8, 10, and 24 hours postdose) | 
| Tmax for CAP |  | Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) | 
| Tmax for 5'DFCR |  | Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) | 
| Tmax for 5'DFUR |  | Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) | 
| Tmax for 5-FU |  | Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) | 
| Terminal Elimination Half-Life (t1/2) for SU, SU012662, and Total Drug (SU + SU012662) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Day 14 of Cycle 1 (predose and 2, 4, 6, 8, 10, and 24 hours postdose) | 
| t1/2 for CAP | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) | 
| t1/2 for 5'DFCR | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) | 
| t1/2 for 5'DFUR | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) | 
| t1/2 for 5-FU | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) | 
| Area Under the Curve From Time 0 to 24 Hours Postdose (AUC [0-24]) for SU, SU012662, and Total Drug (SU + SU012662) | Area under the plasma concentration-time curve from time 0 to 24 hours postdose (0-24), also considered the AUC between doses at steady state. | Day 14 of Cycle 1 (predose and 2, 4, 6, 8, 10, and 24 hours postdose) | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]: CAP, 5'DFCR, 5'DFUR, and 5-FU | AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (predose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). | Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) | 
| Area Under the Curve From Time Zero to 12 Hours [AUC (12)] for CAP, 5'DFCR, 5'DFUR, and 5-FU | AUC (12) = Area under the plasma concentration versus time curve from time zero (predose) to the extrapolated time 12 hours postdose. It is obtained from AUC (0 - last) plus AUC (last - 12) | Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for CAP | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) and Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours) | 
| AUClast for 5'DFCR | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) and Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours) | 
| AUClast for 5'DFUR | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) and Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours) | 
| AUClast for 5-FU | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) and Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours) | 
| Percentage of Participants With Objective Response | Percentage 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 ≥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) | DR defined as time from start of first documented objective tumor response (CR or PR) to first documented objective tumor progression or death due to any cause, whichever occurs first. | Baseline up to Month 15 | 
| Progression-Free Survival (PFS) | PFS defined as time 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. | Baseline up to Month 15 |