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

Phase 1

Completed

Conditions: Stomach Neoplasms

Interventions: Drug: capecitabine
Drug: oxaliplatin
Drug: cisplatin
Drug: sunitinib malate

Registration Number: NCT00555620

Lead Sponsor: Pfizer

Brief Summary: 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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 76

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	capecitabine	-
A	oxaliplatin	-
A	sunitinib malate	-
B	capecitabine	-
B	cisplatin	-
B	sunitinib malate	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With First-cycle Dose Limiting Toxicities (DLTs)	Baseline up to Day 21	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.

Secondary Outcome Measures

Name	Time	Method
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)	Day 14 of Cycle 1 (predose and 2, 4, 6, 8, 10, and 24 hours postdose)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
t1/2 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)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
t1/2 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)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
t1/2 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)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
t1/2 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)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Area Under the Curve From Time 0 to 24 Hours Postdose (AUC [0-24]) for SU, SU012662, and Total Drug (SU + SU012662)	Day 14 of Cycle 1 (predose and 2, 4, 6, 8, 10, and 24 hours postdose)	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.
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]: CAP, 5'DFCR, 5'DFUR, and 5-FU	Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose)	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 - ∞).
Area Under the Curve From Time Zero to 12 Hours [AUC (12)] for CAP, 5'DFCR, 5'DFUR, and 5-FU	Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose)	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)
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for CAP	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)	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
AUClast for 5'DFCR	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)	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
AUClast for 5'DFUR	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)	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
AUClast for 5-FU	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)	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Percentage of Participants With Objective Response	Baseline, Day 21 of every even-numbered cycle up to 15 months	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.
Duration of Response (DR)	Baseline up to Month 15	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.
Progression-Free Survival (PFS)	Baseline up to Month 15	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.