Stomach Neoplasms
Conditions
Keywords
chemotherapy, combination
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.
Interventions
DRUGCisplatin
Cisplatin 60 mg/m2 on day 1 of each 28 day cycle
DRUGS-1
S-1 80 mg/m2 on days 1-21 of each 28 day cycle
DRUGSunitinib
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
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With First Cycle Dose-limiting Toxicities (DLTs) | Cycle 1 (Baseline to Week 4) | A DLT is any of a predefined set of unacceptable adverse events, regardless of cause. DLTs were assessed during the first cycle (4 weeks). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Day 1 of Cycles 1 and 2 (pre-dose, 2, 4, 6, 8, 10, and 24 hours post-dose) | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) |
| 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 | Day 1 of Cycles 1 and 2 (pre-dose, 1, 2, 4, 6, 8, and 10 hours post-dose) | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) |
| 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) | — |
| 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) | — |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) 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 plasma concentration time-curve from zero to the last measured concentration (AUClast) |
| Number of Participants With Objective Response | Baseline up to 739 days | 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. |
| Number of Participants With Clinical Benefit Response (CBR) | Baseline up to 739 days | 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. |
| Duration of Response (DR) | Baseline up to 739 days | 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). |
| Progression-Free Survival (PFS) | Baseline up to 739 days | 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) |
| Time to Progression (TTP) | Baseline up to 739 days | 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). |
| 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) | — |
Countries
Japan
Participant flow
Pre-assignment details
Three to 6 participants at each dose regimen were to be initially assessed for dose limiting toxicity (dose escalation cohort) and 10 participants were added to the maximum tolerated dose (MTD) group after MTD was determined at Sunitinib 25 mg once daily for 2 weeks followed by 2 weeks off-treatment (Schedule 2/2) regimen (MTD expansion cohort).
Participants by arm
| Arm | Count |
|---|---|
| Sunitinib 25 mg CDD + S-1 + Cisplatin Study drugs were administered at following regimens in repeating 4 week cycles; Sunitinib at dose of 25 mg orally once daily continuously (CDD), S-1 at the starting dose of 80-120 mg/day based on body surface area as a twice daily for 3 weeks followed by 1 week off-treatment, cisplatin was administered once at 60 mg/m\^2 on Day 1 of each 4 week cycle. | 4 |
| Sunitinib 25 mg 2/2 + S-1 + Cisplatin (All) Study drugs were administered at following regimens in repeating 4 week cycles; Sunitinib at dose of 25 mg orally once daily for 2 weeks followed by 2 weeks off-treatment (Schedule 2/2), S-1 at the starting dose of 80-120 mg/day based on body surface area as a twice daily for 3 weeks followed by 1 week off-treatment, cisplatin was administered once at 60 mg/m\^2 on Day 1 (dose escalation cohort) or Day 2 (dose expansion cohort) of each 4 week cycle. Dose expansion cohort was added after the maximum tolerated dose (MTD) was determined from the dose limiting toxicity (DLT) evaluation. | 16 |
| Sunitinib 37.5 mg 2/2 + S-1 + Cisplatin Study drugs were administered at following regimens in repeating 4 week cycles; Sunitinib at dose of 37.5 mg orally once daily for 2 weeks followed by 2 weeks off-treatment (Schedule 2/2), S-1 at the starting dose of 80-120 mg/day based on body surface area as a twice daily for 3 weeks followed by 1 week off-treatment, cisplatin was administered once at 60 mg/m\^2 on Day 1 of each 4 week cycle. | 6 |
| Sunitinib 12.5 mg CDD + S-1 + Cisplatin Study drugs were administered at following regimens in repeating 4 week cycles; Sunitinib at dose of 12.5 mg orally once daily continuously (CDD), S-1 at the starting dose of 80-120 mg/day based on body surface area as a twice daily for 3 weeks followed by 1 week off -treatment, cisplatin was administered once at 60 mg/m\^2 on Day 1 of each 4 week cycle. One participant who was assigned to the sunitinib 25 mg on CDD treatment group inadvertently took sunitinib 12.5 mg/day throughout the study, therefore this participant was analyzed separately in this group. | 1 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 4 | 0 | 1 |
| Overall Study | Global deterioration of health status | 0 | 2 | 0 | 0 |
| Overall Study | Objective progression or relapse | 2 | 9 | 6 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Sunitinib 25 mg CDD + S-1 + Cisplatin | Sunitinib 25 mg 2/2 + S-1 + Cisplatin (All) | Sunitinib 37.5 mg 2/2 + S-1 + Cisplatin | Sunitinib 12.5 mg CDD + S-1 + Cisplatin | Total |
|---|---|---|---|---|---|
| Age, Continuous | 60.8 years STANDARD_DEVIATION 12.8 | 56.8 years STANDARD_DEVIATION 11.4 | 54.8 years STANDARD_DEVIATION 16.6 | 64 years STANDARD_DEVIATION 0 | 57.2 years STANDARD_DEVIATION 12.3 |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 2 Participants | 1 Participants | 8 Participants |
| Sex: Female, Male Male | 2 Participants | 13 Participants | 4 Participants | 0 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 4 | 16 / 16 | 6 / 6 | 1 / 1 |
| serious Total, serious adverse events | 2 / 4 | 8 / 16 | 2 / 6 | 1 / 1 |
Outcome results
Primary
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).
Time frame: Cycle 1 (Baseline to Week 4)
Population: DLT Evaluation Set consisted of participants who were initially enrolled for the determination of maximam tolerated dose (MTD), and either 'experienced DLT' or 'received all of the Day 1 chemotherapy, received at least 80% of their sunitinib doses, and at least 80% of S-1 doses'.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Number of Participants With First Cycle Dose-limiting Toxicities (DLTs) | 2 participants |
| Sunitinib 25 mg 2/2 + S-1 + Cisplatin (All) | Number of Participants With First Cycle Dose-limiting Toxicities (DLTs) | 1 participants |
| Sunitinib 37.5 mg 2/2 + S-1 + Cisplatin | Number of Participants With First Cycle Dose-limiting Toxicities (DLTs) | 3 participants |
Secondary
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)
Time frame: Day 1 of Cycles 1 and 2 (pre-dose, 2, 4, 6, 8, 10, and 24 hours post-dose)
Population: Participants who received Sunitinib and had sufficient plasma concentration data for calculation of pharmacokinetic parameters
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) | Cycle 1 Day 1: Sunitinib (Sunitinib Alone) | 214.6 ng*h/mL | Standard Deviation 61.682 |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) | Cycle 2 Day 1: Sunitinib (Sunitinib+S-1+Cisplatin) | 211.9 ng*h/mL | Standard Deviation 46.092 |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) | Cycle 1 Day 1: SU-012662 (Sunitinib Alone) | 39.77 ng*h/mL | Standard Deviation 12.857 |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) | Cycle 2 Day 1: SU-012662 (Sunitinib+S-1+Cisplatin) | 44.83 ng*h/mL | Standard Deviation 24.046 |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) | Cycle 1 Day 1: Total Drug (Sunitinib Alone) | 254.4 ng*h/mL | Standard Deviation 70.913 |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) | Cycle 2 Day 1:Total Drug (Sunitinib+S-1+Cisplatin) | 257.0 ng*h/mL | Standard Deviation 59.324 |
Secondary
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)
Time frame: Day 1 of Cycles 1 and 2 (pre-dose, 1, 2, 4, 6, 8, and 10 hours post-dose)
Population: Participants who received S-1 and had sufficient plasma concentration data for calculation of pharmacokinetic parameters
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Tegafur and 5-FU | Cycle 1 Day 1: Tegafur (S-1 + Cisplatin) | 8314 ng*h/mL | Standard Deviation 726.38 |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Tegafur and 5-FU | Cycle 2 Day 1: Tegafur (Sunitinib+S-1+Cisplatin) | 9182 ng*h/mL | Standard Deviation 819.65 |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Tegafur and 5-FU | Cycle 1 Day 1: 5-FU (S-1 + Cisplatin) | 582.4 ng*h/mL | Standard Deviation 109.12 |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Tegafur and 5-FU | Cycle 2 Day 1: 5-FU (Sunitinib+S-1+Cisplatin) | 494.8 ng*h/mL | Standard Deviation 124.14 |
Secondary
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)
Time frame: Day 1 of Cycles 1 and 2 (pre-dose, 0.5, 1, 2, 8, and 22 hours after completing infusion)
Population: Participants who received cisplatin and had sufficient plasma concentration data for calculation of pharmacokinetic parameters
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Total Platinum and Free Platinum | Cycle 1 Day 1: Total (S-1 + Cisplatin) | 29020 ng*h/mL | Standard Deviation 2070.5 |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Total Platinum and Free Platinum | Cycle 2 Day1: Total (Sunitinib+S-1+Cisplatin) | 33000 ng*h/mL | Standard Deviation 2192 |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Total Platinum and Free Platinum | Cycle 1 Day 1: Free (S-1 + Cisplatin) | 967.8 ng*h/mL | Standard Deviation 332.03 |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Total Platinum and Free Platinum | Cycle 2 Day 1:Free (Sunitinib+S-1+Cisplatin) | 1154 ng*h/mL | Standard Deviation 417.55 |
Secondary
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).
Time frame: Baseline up to 739 days
Population: A subgroup of participants with an objective tumor response among Full Analysis Set consisted of all participants enrolled in the study who received at least 1 dose of study medication (cisplatin, S-1 or sunitinib)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Duration of Response (DR) | 5.7 Months |
| Sunitinib 25 mg 2/2 + S-1 + Cisplatin (All) | Duration of Response (DR) | 10.4 Months |
| Sunitinib 37.5 mg 2/2 + S-1 + Cisplatin | Duration of Response (DR) | 5.0 Months |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662)
Time frame: Day 1 of Cycles 1 and 2 (pre-dose, 2, 4, 6, 8, 10, and 24 hours post-dose)
Population: Participants who received Sunitinib and had sufficient plasma concentration data for calculation of pharmacokinetic parameters
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Maximum Observed Plasma Concentration (Cmax) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) | Cycle 1 Day 1: Sunitinib (Sunitinib Alone) | 14.47 nanogram per milliliter (ng/mL) | Standard Deviation 5.3414 |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Maximum Observed Plasma Concentration (Cmax) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) | Cycle 2 Day 1:Sunitinib (Sunitinib+S-1+Cisplatin) | 13.14 nanogram per milliliter (ng/mL) | Standard Deviation 3.1675 |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Maximum Observed Plasma Concentration (Cmax) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) | Cycle 1 Day 1: SU-012662 (Sunitinib Alone) | 2.487 nanogram per milliliter (ng/mL) | Standard Deviation 1.1515 |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Maximum Observed Plasma Concentration (Cmax) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) | Cycle 2 Day 1:SU-012662(Sunitinib+S-1+Cisplatin) | 2.331 nanogram per milliliter (ng/mL) | Standard Deviation 1.2943 |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Maximum Observed Plasma Concentration (Cmax) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) | Cycle1 Day 1:Total Drug (Sunitinib Alone) | 16.86 nanogram per milliliter (ng/mL) | Standard Deviation 6.3194 |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Maximum Observed Plasma Concentration (Cmax) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) | Cycle 2 Day 1:Total Drug(Sunitinib+S-1+Cisplatin) | 15.41 nanogram per milliliter (ng/mL) | Standard Deviation 3.7667 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Tegafur and 5-FU
Time frame: Day 1 of Cycles 1 and 2 (pre-dose, 1, 2, 4, 6, 8, and 10 hours post-dose)
Population: Participants who received S-1 and had sufficient plasma concentration data for calculation of pharmacokinetic parameters
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Maximum Observed Plasma Concentration (Cmax) of Tegafur and 5-FU | Cycle 2 Day 1: Tegafur (Sunitinib+S-1+Cisplatin) | 1540 nanogram per milliliter (ng/mL) | Standard Deviation 184.39 |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Maximum Observed Plasma Concentration (Cmax) of Tegafur and 5-FU | Cycle 1 Day 1: Tegafur (S-1 + Cisplatin) | 1500 nanogram per milliliter (ng/mL) | Standard Deviation 147.65 |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Maximum Observed Plasma Concentration (Cmax) of Tegafur and 5-FU | Cycle 1 Day 1: 5-FU (S-1 + Cisplatin) | 144.4 nanogram per milliliter (ng/mL) | Standard Deviation 33.901 |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Maximum Observed Plasma Concentration (Cmax) of Tegafur and 5-FU | Cycle 2 Day 1: 5-FU (Sunitinib+S-1+Cisplatin) | 105.7 nanogram per milliliter (ng/mL) | Standard Deviation 19.318 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Total Platinum and Free Platinum
Time frame: Day 1 of Cycles 1 and 2 (pre-dose, 0.5, 1, 2, 8, and 22 hours after completing infusion)
Population: Participants who received cisplatin and had sufficient plasma concentration data for calculation of pharmacokinetic parameters
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Maximum Observed Plasma Concentration (Cmax) of Total Platinum and Free Platinum | Cycle 1 Day 1: Total (S-1 + Cisplatin) | 1794 nanogram per milliliter (ng/mL) | Standard Deviation 140.11 |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Maximum Observed Plasma Concentration (Cmax) of Total Platinum and Free Platinum | Cycle 2 Day1: Total (Sunitinib+S-1+Cisplatin) | 1984 nanogram per milliliter (ng/mL) | Standard Deviation 72.319 |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Maximum Observed Plasma Concentration (Cmax) of Total Platinum and Free Platinum | Cycle 1 Day 1: Free (S-1 + Cisplatin) | 177.8 nanogram per milliliter (ng/mL) | Standard Deviation 121.47 |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Maximum Observed Plasma Concentration (Cmax) of Total Platinum and Free Platinum | Cycle 2 Day 1:Free (Sunitinib+S-1+Cisplatin) | 186.9 nanogram per milliliter (ng/mL) | Standard Deviation 139.45 |
Secondary
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.
Time frame: Baseline up to 739 days
Population: Full Analysis Set consisted of all participants enrolled in the study who received at least 1 dose of study medication (cisplatin, S-1 or sunitinib).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Number of Participants With Clinical Benefit Response (CBR) | 2 participants |
| Sunitinib 25 mg 2/2 + S-1 + Cisplatin (All) | Number of Participants With Clinical Benefit Response (CBR) | 12 participants |
| Sunitinib 37.5 mg 2/2 + S-1 + Cisplatin | Number of Participants With Clinical Benefit Response (CBR) | 4 participants |
| Sunitinib 12.5 mg CDD + S-1 + Cisplatin | Number of Participants With Clinical Benefit Response (CBR) | 0 participants |
Secondary
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.
Time frame: Baseline up to 739 days
Population: Full Analysis Set consisted of all participants enrolled in the study who received at least 1 dose of study medication (cisplatin, S-1 or sunitinib)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Number of Participants With Objective Response | 2 participants |
| Sunitinib 25 mg 2/2 + S-1 + Cisplatin (All) | Number of Participants With Objective Response | 6 participants |
| Sunitinib 37.5 mg 2/2 + S-1 + Cisplatin | Number of Participants With Objective Response | 2 participants |
| Sunitinib 12.5 mg CDD + S-1 + Cisplatin | Number of Participants With Objective Response | 0 participants |
Secondary
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)
Time frame: Baseline up to 739 days
Population: Full Analysis Set consisted of all participants enrolled in the study who received at least 1 dose of study medication (cisplatin, S-1 or sunitinib).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Progression-Free Survival (PFS) | 7.1 Months |
| Sunitinib 25 mg 2/2 + S-1 + Cisplatin (All) | Progression-Free Survival (PFS) | 12.5 Months |
| Sunitinib 37.5 mg 2/2 + S-1 + Cisplatin | Progression-Free Survival (PFS) | 5.8 Months |
Secondary
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).
Time frame: Baseline up to 739 days
Population: Full Analysis Set consisted of all participants enrolled in the study who received at least 1 dose of study medication (cisplatin, S-1 or sunitinib).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Time to Progression (TTP) | 7.1 Months |
| Sunitinib 25 mg 2/2 + S-1 + Cisplatin (All) | Time to Progression (TTP) | 12.5 Months |
| Sunitinib 37.5 mg 2/2 + S-1 + Cisplatin | Time to Progression (TTP) | 5.8 Months |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662)
Time frame: Day 1 of Cycles 1 and 2 (pre-dose, 2, 4, 6, 8, 10, and 24 hours post-dose)
Population: Participants who received Sunitinib and had sufficient plasma concentration data for calculation of pharmacokinetic parameters
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) | Cycle 1 Day 1: Sunitinib ( Sunitinib Alone) | 5.97 hrs |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) | Cycle 2 Day 1: Sunitinib (Sunitinib+S-1+Cisplatin) | 7.97 hrs |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) | Cycle 1 Day 1: SU-012662 ( Sunitinib Alone) | 8.00 hrs |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) | Cycle 2 Day 1: SU-012662 (Sunitinib+S-1+Cisplatin) | 9.25 hrs |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) | Cycle1 Day1:Total Drug ( Sunitinib Alone) | 5.97 hrs |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) | Cycle 2 Day 1:Total Drug (Sunitinib+S-1+Cisplatin) | 7.92 hrs |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tegafur and 5-FU
Time frame: Day 1 of Cycles 1 and 2 (pre-dose, 1, 2, 4, 6, 8, and 10 hours post-dose)
Population: Participants who received S-1 and had sufficient plasma concentration data for calculation of pharmacokinetic parameters
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tegafur and 5-FU | Cycle 1 Day 1: Tegafur (S-1 + Cisplatin) | 1.98 hrs |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tegafur and 5-FU | Cycle 2 Day 1: Tegafur (Sunitinib+S-1+Cisplatin) | 2.00 hrs |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tegafur and 5-FU | Cycle 1 Day 1:5-FU (S-1 + Cisplatin) | 2.00 hrs |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tegafur and 5-FU | Cycle 2 Day 1: 5-FU (Sunitinib+S-1+Cisplatin) | 2.05 hrs |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Total Platinum and Free Platinum
Time frame: Day 1 of Cycles 1 and 2 (pre-dose, 0.5, 1, 2, 8, and 22 hours after completing infusion)
Population: Participants who received cisplatin and had sufficient plasma concentration data for calculation of pharmacokinetic parameters
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Total Platinum and Free Platinum | Cycle 1 Day 1: Total (S-1 + Cisplatin) | 2.65 hrs |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Total Platinum and Free Platinum | Cycle 2 Day1: Total (Sunitinib+S-1+Cisplatin) | 2.68 hrs |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Total Platinum and Free Platinum | Cycle 1 Day 1: Free (S-1 + Cisplatin) | 2.65 hrs |
| Sunitinib 25 mg CDD + S-1 + Cisplatin | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Total Platinum and Free Platinum | Cycle 2 Day 1:Free (Sunitinib+S-1+Cisplatin) | 2.68 hrs |