Study Of Sunitinib With S-1 And Cisplatin For Gastric Cancer
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00553696
Collaborator
(none)
27
3
1
76
9
0.1
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
27 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1 Study Of Sunitinib In Combination With S-1 And Cisplatin In Patients With Advanced Or Metastatic Gastric Cancer
Study Start Date
:
Nov 1, 2007
Actual Primary Completion Date
:
Jul 1, 2009
Actual Study Completion Date
:
Mar 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: A
|
Drug: Cisplatin
Cisplatin 60 mg/m2 on day 1 of each 28 day cycle
Drug: S-1
S-1 80 mg/m2 on days 1-21 of each 28 day cycle
Drug: Sunitinib
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
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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) [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)]
- 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 [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).
Eligibility Criteria
Criteria
Ages Eligible for Study:
20 Years
and Older
Sexes Eligible for Study:
All
Accepts 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Aichi cancer center central hospital / Medical Oncology | Nagoya | Aichi | Japan | 464-8681 |
| 2 | Saku Central Hospital, GI Devision | Saku | Nagano | Japan | |
| 3 | Shizuoka Cancer Center | Suntougun | Shizuoka | Japan | 411-8777 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00553696
Other Study ID Numbers:
- A6181127
First Posted:
Nov 4, 2007
Last Update Posted:
Mar 13, 2015
Last Verified:
Mar 1, 2015
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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). |
| Arm/Group Title | 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 |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Period Title: Overall Study | ||||
| STARTED | 4 | 16 | 6 | 1 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 4 | 16 | 6 | 1 |
Baseline Characteristics
| Arm/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | Total of all reporting groups |
| Overall Participants | 4 | 16 | 6 | 1 | 27 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
60.8
(12.8)
|
56.8
(11.4)
|
54.8
(16.6)
|
64
(0)
|
57.2
(12.3)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
2
50%
|
3
18.8%
|
2
33.3%
|
1
100%
|
8
29.6%
|
| Male |
2
50%
|
13
81.3%
|
4
66.7%
|
0
0%
|
19
70.4%
|
Outcome Measures
| Title | Number of Participants With First Cycle Dose-limiting Toxicities (DLTs) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Sunitinib 25 mg CDD + S-1 + Cisplatin | Sunitinib 25 mg 2/2 + S-1 + Cisplatin (Dose Escalation Cohort) | Sunitinib 37.5 mg 2/2 + S-1 + Cisplatin |
|---|---|---|---|
| Arm/Group Description | 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. | 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 regimen 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. | 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. |
| Measure Participants | 4 | 6 | 6 |
| Number [participants] |
2
50%
|
1
6.3%
|
3
50%
|
| Title | Maximum Observed Plasma Concentration (Cmax) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) |
|---|---|
| Description | |
| Time Frame | Day 1 of Cycles 1 and 2 (pre-dose, 2, 4, 6, 8, 10, and 24 hours post-dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received Sunitinib and had sufficient plasma concentration data for calculation of pharmacokinetic parameters |
| Arm/Group Title | Sunitinib 25 mg 2/2 + Cisplatin + S-1 (MTD Expansion Cohort) |
|---|---|
| Arm/Group Description | Subset of Sunitinib 25 mg 2/2 + Cisplatin + S-1 arm consisted of participants who were additionally enrolled after the maximum tolerated dose (MTD) of sunitinib was determined as 25 mg orally once daily for 2 weeks followed by 2 weeks off-treatment |
| Measure Participants | 7 |
| Cycle 1 Day 1: Sunitinib (Sunitinib Alone) |
14.47
(5.3414)
|
| Cycle 2 Day 1:Sunitinib (Sunitinib+S-1+Cisplatin) |
13.14
(3.1675)
|
| Cycle 1 Day 1: SU-012662 (Sunitinib Alone) |
2.487
(1.1515)
|
| Cycle 2 Day 1:SU-012662(Sunitinib+S-1+Cisplatin) |
2.331
(1.2943)
|
| Cycle1 Day 1:Total Drug (Sunitinib Alone) |
16.86
(6.3194)
|
| Cycle 2 Day 1:Total Drug(Sunitinib+S-1+Cisplatin) |
15.41
(3.7667)
|
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) |
|---|---|
| Description | |
| Time Frame | Day 1 of Cycles 1 and 2 (pre-dose, 2, 4, 6, 8, 10, and 24 hours post-dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received Sunitinib and had sufficient plasma concentration data for calculation of pharmacokinetic parameters |
| Arm/Group Title | Sunitinib 25 mg 2/2 + Cisplatin + S-1 (MTD Expansion Cohort) |
|---|---|
| Arm/Group Description | Subset of Sunitinib 25 mg 2/2 + Cisplatin + S-1 arm consisted of participants who were additionally enrolled after the maximum tolerated dose (MTD) of sunitinib was determined as 25 mg orally once daily for 2 weeks followed by 2 weeks off-treatment |
| Measure Participants | 7 |
| Cycle 1 Day 1: Sunitinib ( Sunitinib Alone) |
5.97
|
| Cycle 2 Day 1: Sunitinib (Sunitinib+S-1+Cisplatin) |
7.97
|
| Cycle 1 Day 1: SU-012662 ( Sunitinib Alone) |
8.00
|
| Cycle 2 Day 1: SU-012662 (Sunitinib+S-1+Cisplatin) |
9.25
|
| Cycle1 Day1:Total Drug ( Sunitinib Alone) |
5.97
|
| Cycle 2 Day 1:Total Drug (Sunitinib+S-1+Cisplatin) |
7.92
|
| Title | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Sunitinib, SU-012662, and Total Drug (Sunitinib + SU-012662) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received Sunitinib and had sufficient plasma concentration data for calculation of pharmacokinetic parameters |
| Arm/Group Title | Sunitinib 25 mg 2/2 + Cisplatin + S-1 (MTD Expansion Cohort) |
|---|---|
| Arm/Group Description | Subset of Sunitinib 25 mg 2/2 + Cisplatin + S-1 arm consisted of participants who were additionally enrolled after the maximum tolerated dose (MTD) of sunitinib was determined as 25 mg orally once daily for 2 weeks followed by 2 weeks off-treatment |
| Measure Participants | 7 |
| Cycle 1 Day 1: Sunitinib (Sunitinib Alone) |
214.6
(61.682)
|
| Cycle 2 Day 1: Sunitinib (Sunitinib+S-1+Cisplatin) |
211.9
(46.092)
|
| Cycle 1 Day 1: SU-012662 (Sunitinib Alone) |
39.77
(12.857)
|
| Cycle 2 Day 1: SU-012662 (Sunitinib+S-1+Cisplatin) |
44.83
(24.046)
|
| Cycle 1 Day 1: Total Drug (Sunitinib Alone) |
254.4
(70.913)
|
| Cycle 2 Day 1:Total Drug (Sunitinib+S-1+Cisplatin) |
257.0
(59.324)
|
| Title | Maximum Observed Plasma Concentration (Cmax) of Tegafur and 5-FU |
|---|---|
| Description | |
| Time Frame | Day 1 of Cycles 1 and 2 (pre-dose, 1, 2, 4, 6, 8, and 10 hours post-dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received S-1 and had sufficient plasma concentration data for calculation of pharmacokinetic parameters |
| Arm/Group Title | Sunitinib 25 mg 2/2 + S-1 + Cisplatin (All) |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 5 |
| Cycle 1 Day 1: Tegafur (S-1 + Cisplatin) |
1500
(147.65)
|
| Cycle 2 Day 1: Tegafur (Sunitinib+S-1+Cisplatin) |
1540
(184.39)
|
| Cycle 1 Day 1: 5-FU (S-1 + Cisplatin) |
144.4
(33.901)
|
| Cycle 2 Day 1: 5-FU (Sunitinib+S-1+Cisplatin) |
105.7
(19.318)
|
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tegafur and 5-FU |
|---|---|
| Description | |
| Time Frame | Day 1 of Cycles 1 and 2 (pre-dose, 1, 2, 4, 6, 8, and 10 hours post-dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received S-1 and had sufficient plasma concentration data for calculation of pharmacokinetic parameters |
| Arm/Group Title | Sunitinib 25 mg 2/2 + S-1 + Cisplatin (All) |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 5 |
| Cycle 1 Day 1: Tegafur (S-1 + Cisplatin) |
1.98
|
| Cycle 2 Day 1: Tegafur (Sunitinib+S-1+Cisplatin) |
2.00
|
| Cycle 1 Day 1:5-FU (S-1 + Cisplatin) |
2.00
|
| Cycle 2 Day 1: 5-FU (Sunitinib+S-1+Cisplatin) |
2.05
|
| Title | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Tegafur and 5-FU |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received S-1 and had sufficient plasma concentration data for calculation of pharmacokinetic parameters |
| Arm/Group Title | Sunitinib 25 mg 2/2 + S-1 + Cisplatin (All) |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 5 |
| Cycle 1 Day 1: Tegafur (S-1 + Cisplatin) |
8314
(726.38)
|
| Cycle 2 Day 1: Tegafur (Sunitinib+S-1+Cisplatin) |
9182
(819.65)
|
| Cycle 1 Day 1: 5-FU (S-1 + Cisplatin) |
582.4
(109.12)
|
| Cycle 2 Day 1: 5-FU (Sunitinib+S-1+Cisplatin) |
494.8
(124.14)
|
| Title | Maximum Observed Plasma Concentration (Cmax) of Total Platinum and Free Platinum |
|---|---|
| Description | |
| Time Frame | Day 1 of Cycles 1 and 2 (pre-dose, 0.5, 1, 2, 8, and 22 hours after completing infusion) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received cisplatin and had sufficient plasma concentration data for calculation of pharmacokinetic parameters |
| Arm/Group Title | Sunitinib 25 mg 2/2 + S-1 + Cisplatin (All) |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 5 |
| Cycle 1 Day 1: Total (S-1 + Cisplatin) |
1794
(140.11)
|
| Cycle 2 Day1: Total (Sunitinib+S-1+Cisplatin) |
1984
(72.319)
|
| Cycle 1 Day 1: Free (S-1 + Cisplatin) |
177.8
(121.47)
|
| Cycle 2 Day 1:Free (Sunitinib+S-1+Cisplatin) |
186.9
(139.45)
|
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Total Platinum and Free Platinum |
|---|---|
| Description | |
| Time Frame | Day 1 of Cycles 1 and 2 (pre-dose, 0.5, 1, 2, 8, and 22 hours after completing infusion) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received cisplatin and had sufficient plasma concentration data for calculation of pharmacokinetic parameters |
| Arm/Group Title | Sunitinib 25 mg 2/2 + S-1 + Cisplatin (All) |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 5 |
| Cycle 1 Day 1: Total (S-1 + Cisplatin) |
2.65
|
| Cycle 2 Day1: Total (Sunitinib+S-1+Cisplatin) |
2.68
|
| Cycle 1 Day 1: Free (S-1 + Cisplatin) |
2.65
|
| Cycle 2 Day 1:Free (Sunitinib+S-1+Cisplatin) |
2.68
|
| Title | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Total Platinum and Free Platinum |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received cisplatin and had sufficient plasma concentration data for calculation of pharmacokinetic parameters |
| Arm/Group Title | Sunitinib 25 mg 2/2 + S-1 + Cisplatin (All) |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 5 |
| Cycle 1 Day 1: Total (S-1 + Cisplatin) |
29020
(2070.5)
|
| Cycle 2 Day1: Total (Sunitinib+S-1+Cisplatin) |
33000
(2192.0)
|
| Cycle 1 Day 1: Free (S-1 + Cisplatin) |
967.8
(332.03)
|
| Cycle 2 Day 1:Free (Sunitinib+S-1+Cisplatin) |
1154
(417.55)
|
| Title | Number of Participants With Objective Response |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 4 | 16 | 6 | 1 |
| Number [participants] |
2
50%
|
6
37.5%
|
2
33.3%
|
0
0%
|
| Title | Number of Participants With Clinical Benefit Response (CBR) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 4 | 16 | 6 | 1 |
| Number [participants] |
2
50%
|
12
75%
|
4
66.7%
|
0
0%
|
| Title | Duration of Response (DR) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 2 | 6 | 2 | 0 |
| Median (95% Confidence Interval) [Months] |
5.7
|
10.4
|
5.0
|
| Title | Progression-Free Survival (PFS) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 2 | 6 | 2 | 0 |
| Median (95% Confidence Interval) [Months] |
7.1
|
12.5
|
5.8
|
| Title | Time to Progression (TTP) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 2 | 6 | 2 | 0 |
| Median (95% Confidence Interval) [Months] |
7.1
|
12.5
|
5.8
|
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. | |||||||
| Arm/Group Title | 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 | ||||
| Arm/Group Description | 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. | 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. | 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. | 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. | ||||
All Cause Mortality |
||||||||
| 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 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| 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 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/4 (50%) | 8/16 (50%) | 2/6 (33.3%) | 1/1 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Disseminated intravascular coagulation | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Febrile neutropenia | 1/4 (25%) | 3/16 (18.8%) | 2/6 (33.3%) | 0/1 (0%) | ||||
| Neutropenia | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Cardiac disorders | ||||||||
| Bradycardia | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Gastrointestinal haemorrhage | 1/4 (25%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| General disorders | ||||||||
| Pyrexia | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Cholecystitis acute | 1/4 (25%) | 0/16 (0%) | 0/6 (0%) | 0/1 (0%) | ||||
| Infections and infestations | ||||||||
| Lung infection | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Neutropenic infection | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Investigations | ||||||||
| Blood creatinine increased | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Haemoglobin decreased | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Platelet count decreased | 2/4 (50%) | 2/16 (12.5%) | 0/6 (0%) | 0/1 (0%) | ||||
| White blood cell count decreased | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Dehydration | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Nervous system disorders | ||||||||
| Cerebral infarction | 0/4 (0%) | 0/16 (0%) | 0/6 (0%) | 1/1 (100%) | ||||
| Renal and urinary disorders | ||||||||
| Renal impairment | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| 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 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/4 (100%) | 16/16 (100%) | 6/6 (100%) | 1/1 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 1/4 (25%) | 3/16 (18.8%) | 1/6 (16.7%) | 1/1 (100%) | ||||
| Febrile neutropenia | 0/4 (0%) | 2/16 (12.5%) | 0/6 (0%) | 1/1 (100%) | ||||
| Leukopenia | 0/4 (0%) | 3/16 (18.8%) | 1/6 (16.7%) | 1/1 (100%) | ||||
| Lymphopenia | 0/4 (0%) | 0/16 (0%) | 1/6 (16.7%) | 1/1 (100%) | ||||
| Neutropenia | 0/4 (0%) | 3/16 (18.8%) | 1/6 (16.7%) | 1/1 (100%) | ||||
| Thrombocytopenia | 0/4 (0%) | 3/16 (18.8%) | 1/6 (16.7%) | 1/1 (100%) | ||||
| Cardiac disorders | ||||||||
| Bradycardia | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Palpitations | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Ventricular extrasystoles | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Tinnitus | 1/4 (25%) | 1/16 (6.3%) | 2/6 (33.3%) | 0/1 (0%) | ||||
| Eye disorders | ||||||||
| Conjunctival haemorrhage | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Conjunctivitis | 0/4 (0%) | 2/16 (12.5%) | 0/6 (0%) | 0/1 (0%) | ||||
| Corneal disorder | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Eyelid oedema | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Keratitis | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Lacrimation increased | 0/4 (0%) | 4/16 (25%) | 2/6 (33.3%) | 1/1 (100%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal discomfort | 1/4 (25%) | 0/16 (0%) | 0/6 (0%) | 0/1 (0%) | ||||
| Abdominal distension | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Abdominal pain | 1/4 (25%) | 4/16 (25%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Abdominal pain upper | 1/4 (25%) | 0/16 (0%) | 0/6 (0%) | 0/1 (0%) | ||||
| Cheilitis | 0/4 (0%) | 2/16 (12.5%) | 0/6 (0%) | 0/1 (0%) | ||||
| Constipation | 3/4 (75%) | 12/16 (75%) | 2/6 (33.3%) | 0/1 (0%) | ||||
| Diarrhoea | 4/4 (100%) | 8/16 (50%) | 4/6 (66.7%) | 0/1 (0%) | ||||
| Dry mouth | 0/4 (0%) | 0/16 (0%) | 0/6 (0%) | 1/1 (100%) | ||||
| Dyspepsia | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Gastrointestinal haemorrhage | 1/4 (25%) | 0/16 (0%) | 0/6 (0%) | 0/1 (0%) | ||||
| Haemorrhoidal haemorrhage | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Haemorrhoids | 0/4 (0%) | 2/16 (12.5%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Nausea | 2/4 (50%) | 14/16 (87.5%) | 5/6 (83.3%) | 0/1 (0%) | ||||
| Periodontal disease | 0/4 (0%) | 2/16 (12.5%) | 0/6 (0%) | 1/1 (100%) | ||||
| Stomatitis | 2/4 (50%) | 9/16 (56.3%) | 6/6 (100%) | 0/1 (0%) | ||||
| Tongue coated | 1/4 (25%) | 0/16 (0%) | 0/6 (0%) | 0/1 (0%) | ||||
| Vomiting | 2/4 (50%) | 6/16 (37.5%) | 4/6 (66.7%) | 0/1 (0%) | ||||
| General disorders | ||||||||
| Chest pain | 0/4 (0%) | 0/16 (0%) | 3/6 (50%) | 0/1 (0%) | ||||
| Extravasation | 1/4 (25%) | 0/16 (0%) | 0/6 (0%) | 0/1 (0%) | ||||
| Fatigue | 4/4 (100%) | 14/16 (87.5%) | 5/6 (83.3%) | 1/1 (100%) | ||||
| Influenza like illness | 0/4 (0%) | 3/16 (18.8%) | 2/6 (33.3%) | 0/1 (0%) | ||||
| Oedema | 2/4 (50%) | 3/16 (18.8%) | 3/6 (50%) | 0/1 (0%) | ||||
| Oedema peripheral | 0/4 (0%) | 2/16 (12.5%) | 0/6 (0%) | 1/1 (100%) | ||||
| Pyrexia | 1/4 (25%) | 7/16 (43.8%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Hyperbilirubinaemia | 1/4 (25%) | 4/16 (25%) | 3/6 (50%) | 0/1 (0%) | ||||
| Infections and infestations | ||||||||
| Bronchitis | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Gastroenteritis | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Gingivitis | 1/4 (25%) | 2/16 (12.5%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Infection | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Influenza | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Nasopharyngitis | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Oral candidiasis | 0/4 (0%) | 2/16 (12.5%) | 0/6 (0%) | 0/1 (0%) | ||||
| Oral herpes | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Otitis media | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Paronychia | 0/4 (0%) | 0/16 (0%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Pneumonia | 0/4 (0%) | 3/16 (18.8%) | 0/6 (0%) | 0/1 (0%) | ||||
| Skin infection | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Tinea infection | 0/4 (0%) | 0/16 (0%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Upper respiratory tract infection | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Excoriation | 0/4 (0%) | 2/16 (12.5%) | 0/6 (0%) | 0/1 (0%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 1/4 (25%) | 2/16 (12.5%) | 1/6 (16.7%) | 1/1 (100%) | ||||
| Amylase increased | 0/4 (0%) | 0/16 (0%) | 1/6 (16.7%) | 1/1 (100%) | ||||
| Aspartate aminotransferase increased | 0/4 (0%) | 1/16 (6.3%) | 1/6 (16.7%) | 1/1 (100%) | ||||
| Blood albumin decreased | 1/4 (25%) | 2/16 (12.5%) | 1/6 (16.7%) | 1/1 (100%) | ||||
| Blood alkaline phosphatase abnormal | 0/4 (0%) | 0/16 (0%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Blood alkaline phosphatase increased | 0/4 (0%) | 0/16 (0%) | 1/6 (16.7%) | 1/1 (100%) | ||||
| Blood bilirubin increased | 1/4 (25%) | 3/16 (18.8%) | 2/6 (33.3%) | 0/1 (0%) | ||||
| Blood calcium | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Blood calcium decreased | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 1/1 (100%) | ||||
| Blood creatinine increased | 3/4 (75%) | 2/16 (12.5%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Blood glucose increased | 0/4 (0%) | 0/16 (0%) | 0/6 (0%) | 1/1 (100%) | ||||
| Blood lactate dehydrogenase increased | 0/4 (0%) | 0/16 (0%) | 0/6 (0%) | 1/1 (100%) | ||||
| Blood magnesium decreased | 0/4 (0%) | 3/16 (18.8%) | 0/6 (0%) | 0/1 (0%) | ||||
| Blood phosphorus decreased | 1/4 (25%) | 4/16 (25%) | 0/6 (0%) | 1/1 (100%) | ||||
| Blood potassium decreased | 0/4 (0%) | 2/16 (12.5%) | 0/6 (0%) | 0/1 (0%) | ||||
| Blood sodium decreased | 0/4 (0%) | 0/16 (0%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Blood thyroid stimulating hormone decreased | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Blood thyroid stimulating hormone increased | 0/4 (0%) | 0/16 (0%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Blood urea increased | 0/4 (0%) | 0/16 (0%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Blood uric acid increased | 0/4 (0%) | 2/16 (12.5%) | 0/6 (0%) | 0/1 (0%) | ||||
| C-reactive protein increased | 1/4 (25%) | 0/16 (0%) | 0/6 (0%) | 0/1 (0%) | ||||
| Glucose urine present | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Haemoglobin decreased | 4/4 (100%) | 12/16 (75%) | 5/6 (83.3%) | 0/1 (0%) | ||||
| Lipase increased | 0/4 (0%) | 1/16 (6.3%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Lymphocyte count decreased | 0/4 (0%) | 0/16 (0%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Neutrophil count decreased | 4/4 (100%) | 13/16 (81.3%) | 5/6 (83.3%) | 0/1 (0%) | ||||
| Platelet count decreased | 4/4 (100%) | 12/16 (75%) | 5/6 (83.3%) | 0/1 (0%) | ||||
| Protein total decreased | 1/4 (25%) | 0/16 (0%) | 0/6 (0%) | 1/1 (100%) | ||||
| Weight decreased | 1/4 (25%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Weight increased | 1/4 (25%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| White blood cell count decreased | 4/4 (100%) | 13/16 (81.3%) | 5/6 (83.3%) | 0/1 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 4/4 (100%) | 15/16 (93.8%) | 4/6 (66.7%) | 1/1 (100%) | ||||
| Dehydration | 2/4 (50%) | 2/16 (12.5%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Hyperuricaemia | 1/4 (25%) | 0/16 (0%) | 0/6 (0%) | 0/1 (0%) | ||||
| Hypoalbuminaemia | 1/4 (25%) | 0/16 (0%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Hypokalaemia | 0/4 (0%) | 1/16 (6.3%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Hypomagnesaemia | 1/4 (25%) | 1/16 (6.3%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Hyponatraemia | 0/4 (0%) | 3/16 (18.8%) | 2/6 (33.3%) | 0/1 (0%) | ||||
| Hypophosphataemia | 0/4 (0%) | 1/16 (6.3%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 0/4 (0%) | 2/16 (12.5%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Muscular weakness | 1/4 (25%) | 0/16 (0%) | 0/6 (0%) | 0/1 (0%) | ||||
| Musculoskeletal stiffness | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Nervous system disorders | ||||||||
| Cognitive disorder | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Dysgeusia | 3/4 (75%) | 7/16 (43.8%) | 4/6 (66.7%) | 1/1 (100%) | ||||
| Headache | 0/4 (0%) | 2/16 (12.5%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Neuropathy peripheral | 0/4 (0%) | 2/16 (12.5%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Presyncope | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Sciatica | 1/4 (25%) | 0/16 (0%) | 0/6 (0%) | 0/1 (0%) | ||||
| Psychiatric disorders | ||||||||
| Insomnia | 0/4 (0%) | 5/16 (31.3%) | 2/6 (33.3%) | 0/1 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Proteinuria | 1/4 (25%) | 3/16 (18.8%) | 0/6 (0%) | 0/1 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 2/4 (50%) | 0/16 (0%) | 2/6 (33.3%) | 0/1 (0%) | ||||
| Dysphonia | 1/4 (25%) | 2/16 (12.5%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Dyspnoea | 0/4 (0%) | 0/16 (0%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Epistaxis | 3/4 (75%) | 4/16 (25%) | 6/6 (100%) | 1/1 (100%) | ||||
| Hiccups | 0/4 (0%) | 6/16 (37.5%) | 2/6 (33.3%) | 0/1 (0%) | ||||
| Hypoxia | 0/4 (0%) | 2/16 (12.5%) | 0/6 (0%) | 0/1 (0%) | ||||
| Oropharyngeal pain | 1/4 (25%) | 2/16 (12.5%) | 0/6 (0%) | 0/1 (0%) | ||||
| Pleural effusion | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Rhinitis allergic | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 0/4 (0%) | 2/16 (12.5%) | 2/6 (33.3%) | 0/1 (0%) | ||||
| Dry skin | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Eczema asteatotic | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Haemorrhage subcutaneous | 0/4 (0%) | 0/16 (0%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Hair colour changes | 0/4 (0%) | 0/16 (0%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Palmar-plantar erythrodysaesthesia syndrome | 1/4 (25%) | 4/16 (25%) | 1/6 (16.7%) | 1/1 (100%) | ||||
| Petechiae | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Pruritus | 0/4 (0%) | 1/16 (6.3%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Purpura | 0/4 (0%) | 0/16 (0%) | 0/6 (0%) | 1/1 (100%) | ||||
| Rash | 1/4 (25%) | 5/16 (31.3%) | 3/6 (50%) | 0/1 (0%) | ||||
| Skin discolouration | 3/4 (75%) | 3/16 (18.8%) | 5/6 (83.3%) | 0/1 (0%) | ||||
| Skin fissures | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Skin hyperpigmentation | 1/4 (25%) | 0/16 (0%) | 0/6 (0%) | 0/1 (0%) | ||||
| Toxic skin eruption | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Urticaria | 0/4 (0%) | 0/16 (0%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Yellow skin | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 0/4 (0%) | 1/16 (6.3%) | 1/6 (16.7%) | 0/1 (0%) | ||||
| Hypotension | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
| Orthostatic hypotension | 0/4 (0%) | 1/16 (6.3%) | 0/6 (0%) | 0/1 (0%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00553696
Other Study ID Numbers:
- A6181127
First Posted:
Nov 4, 2007
Last Update Posted:
Mar 13, 2015
Last Verified:
Mar 1, 2015