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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00555672
• Collaborator: (none)
• Enrollment: 34
• Locations: 3
• Arm: 1
• Duration (Months): 24
• Patients Per Site: 11.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Stomach Neoplasms	Drug: 5-fluorouracil; Drug: cisplatin; Drug: sunitinib malate	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Study Of Sunitinib Malate In Combination With Cisplatin And 5-Fluorouracil In Patients With Advanced Gastric Cancer
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: A

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

Outcome Measures

Primary Outcome Measures

1. Number of Participants With First-cycle Dose Limiting Toxicities (DLTs) [Cycle 1 (Baseline to Day 21)]

   The incidence of DLTs assessed during the first cycle (21 days).

Secondary Outcome Measures

1. Maximum Observed Plasma Concentration (Cmax) [Day 1 of Cycle 1 (2, 4, 6, 8, 10, and 24 hours post dose)]

2. Area Under the Curve From Time 0 to 24 Hours Postdose [AUC (0-24)] [Day 1 of Cycle 1 (2, 4, 6, 8, 10, and 24 hours postdose)]

   Area under the plasma concentration versus time curve from time 0 (pre-dose) to 24 hours postdose (0-24).

3. Time to Reach Maximum Observed Plasma Concentration (Tmax) [Day 1 of Cycle 1 (2, 4, 6, 8, 10, and 24 hours post dose)]

   Tmax is the time to first occurrence of maximum observed plasma concentration (Cmax).

4. Steady State Concentration (Css) of 5-Fluorouracil (5-FU) [Day 1 of Cycle 1 (2, 4, and 6 hours post infusion)]

   Steady state plasma concentration of 5-FU equals AUC(2-6) divided by 4, where AUC(2-6) is the area under the plasma concentration versus time curve from time 2 to 6 hours postdose (2-6).

5. Infusion Rate (Zero Order) (R0) of 5-FU [Day 1 of Cycle 1 (2, 4, and 6 hours post infusion)]

   Infusion rate of 5-FU equals total dose divided by infusion time.

6. Clearance (CLss) of 5-FU [Day 1 of Cycle 1 (2, 4, and 6 hours post infusion)]

   Steady state total body clearance equals infusion rate (zero order) divided by steady state plasma concentration of 5-FU (R0/Css).

7. Area Under the Curve From Time 2 to 6 Hours Postdose [AUC (2-6)] of 5-FU [Day 1 of Cycle 1 (2, 4, and 6 hours post infusion)]

   Area under the plasma concentration versus time curve from time 2 to 6 hours postdose (2-6).

8. Number of Participants With Objective Response [Baseline, Day 21 of every even-numbered cycle up to 15 Months]

   Number of participants with an objective response-based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR defined as the disappearance of all target lesions. PR defined as greater than or equal to (≥) 30 percent (%) decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.

9. Duration of Response (DR) [Baseline up to Month 15]

   Time from the first objective documentation of tumor response (confirmed or partial response) to first documented objective tumor progression or death due to any cause, whichever occurrs first. DR calculated as (Months) equals (the end date for DR minus first subsequent confirmed CR or PR plus 1) divided by 30.

10. Progression-Free Survival (PFS) [Baseline up to Month 15]

    Median time (50%) from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. PFS calculated as (Months) equals (first event date minus first dose date plus 1) divided by 30.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• confirmed diagnosis of stomach cancer

• advanced stomach cancer stage IV

• adequate blood chemistry, blood counts and kidney function

• willing to participate to study requirements and to sign an informed consent document

Exclusion Criteria:

• prior chemotherapy for stomach cancer in its advanced stage

• excessive toxicities related to prior therapies

• pregnant or breastfeeding patients

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	L'hospitalet de Llobregat	Barcelona	Spain	08907
2	Pfizer Investigational Site	Barcelona		Spain	08003
3	Pfizer Investigational Site	Madrid		Spain	28041

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00555672
• Other Study ID Numbers: A6181128
• First Posted: Nov 9, 2007
• Last Update Posted: Dec 19, 2011
• Last Verified: Dec 1, 2011

• Additional relevant MeSH terms: Stomach Neoplasms; Fluorouracil; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU	Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU
Arm/Group Description	Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Sunitinib: 37.5 mg oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m^2) on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Period Title: Overall Study
STARTED	24	10
COMPLETED	0	0
NOT COMPLETED	24	10

Baseline Characteristics

Arm/Group Title	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU	Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU	Total
Arm/Group Description	Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Sunitinib: 37.5 mg oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m^2) on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Total of all reporting groups
Overall Participants	24	10	34
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.1 (12.0)	56.4 (10.4)	59.0 (11.5)
Sex: Female, Male (Count of Participants)
Female	7 29.2%	4 40%	11 32.4%
Male	17 70.8%	6 60%	23 67.6%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety: enrolled participants who received at least 1 dose of study drug.

Arm/Group Title	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU	Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU
Arm/Group Description	Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Sunitinib: 37.5 mg oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m^2) on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Measure Participants	24	10
Number [Participants]	1 4.2%	0 0%

2. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax)
Time Frame	Day 1 of Cycle 1 (2, 4, 6, 8, 10, and 24 hours post dose)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK): participants who received Sunitinib and had sufficient plasma concentration data for calculation of PK parameters; N=number of participants contributing to summary statistics. Cmax of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) calculated for at least 6 individual participants treated at maximum tolerated dose.

Arm/Group Title	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU
Arm/Group Description	Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Measure Participants	9
Sunitinib	16.8 (8.19)
SU012662 (metabolite of Sunitinib)	2.24 (1.29)
Total Drug (Sunitinib + SU012662)	19.0 (9.35)

3. Secondary Outcome

Title	Area Under the Curve From Time 0 to 24 Hours Postdose [AUC (0-24)]
Description	Area under the plasma concentration versus time curve from time 0 (pre-dose) to 24 hours postdose (0-24).
Time Frame	Day 1 of Cycle 1 (2, 4, 6, 8, 10, and 24 hours postdose)

Outcome Measure Data

Analysis Population Description

PK; N=the number of participants contributing to the summary statistics. AUC(0-24) of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) calculated for at least 6 individual participants treated at the maximum tolerated dose (MTD; 25 mg Sunitinib).

Arm/Group Title	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU
Arm/Group Description	Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Measure Participants	9
Sunitinib	249 (127)
SU012662 (metabolite of Sunitinib)	34.0 (19.5)
Total Drug (Sunitinib + SU012662)	283 (144)

4. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax)
Description	Tmax is the time to first occurrence of maximum observed plasma concentration (Cmax).
Time Frame	Day 1 of Cycle 1 (2, 4, 6, 8, 10, and 24 hours post dose)

Outcome Measure Data

Analysis Population Description

PK; N=the number of participants contributing to the summary statistics. Tmax of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) calculated for at least 6 individual participants treated at the MTD (25 mg Sunitinib).

Arm/Group Title	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU
Arm/Group Description	Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Measure Participants	9
Sunitinib	4.00
SU012662 (metabolite of Sunitinib)	4.00
Total Drug (Sunitinib + SU012662)	4.00

5. Secondary Outcome

Title	Steady State Concentration (Css) of 5-Fluorouracil (5-FU)
Description	Steady state plasma concentration of 5-FU equals AUC(2-6) divided by 4, where AUC(2-6) is the area under the plasma concentration versus time curve from time 2 to 6 hours postdose (2-6).
Time Frame	Day 1 of Cycle 1 (2, 4, and 6 hours post infusion)

Outcome Measure Data

Analysis Population Description

PK; N=number of participants contributing to the summary statistics. Css calculated for at least 6 individual participants treated at the MTD (25 mg Sunitinib).

Arm/Group Title	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU
Arm/Group Description	Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Measure Participants	6
Mean (Standard Deviation) [ng/mL]	593 (433)

6. Secondary Outcome

Title	Infusion Rate (Zero Order) (R0) of 5-FU
Description	Infusion rate of 5-FU equals total dose divided by infusion time.
Time Frame	Day 1 of Cycle 1 (2, 4, and 6 hours post infusion)

Outcome Measure Data

Analysis Population Description

PK; N= number of participants contributing to the summary statistics. R0 calculated for at least 6 individual participants treated at the MTD (25 mg Sunitinib).

Arm/Group Title	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU
Arm/Group Description	Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Measure Participants	6
Mean (Standard Deviation) [mg/hr]	68.2 (12.5)

7. Secondary Outcome

Title	Clearance (CLss) of 5-FU
Description	Steady state total body clearance equals infusion rate (zero order) divided by steady state plasma concentration of 5-FU (R0/Css).
Time Frame	Day 1 of Cycle 1 (2, 4, and 6 hours post infusion)

Outcome Measure Data

Analysis Population Description

PK; N=the number of participants contributing to the summary statistics. CLss calculated for at least 6 individual participants treated at the MTD (25 mg Sunitinib).

Arm/Group Title	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU
Arm/Group Description	Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Measure Participants	6
Mean (Standard Deviation) [Liters per hour]	161 (93.2)

8. Secondary Outcome

Title	Area Under the Curve From Time 2 to 6 Hours Postdose [AUC (2-6)] of 5-FU
Description	Area under the plasma concentration versus time curve from time 2 to 6 hours postdose (2-6).
Time Frame	Day 1 of Cycle 1 (2, 4, and 6 hours post infusion)

Outcome Measure Data

Analysis Population Description

PK; N=number of participants contributing to the summary statistics. Css calculated for at least 6 individual participants treated at the MTD (25 mg Sunitinib).

Arm/Group Title	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU
Arm/Group Description	Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Measure Participants	6
Mean (Standard Deviation) [ng*h/mL]	2372 (1729)

9. Secondary Outcome

Title	Number of Participants With Objective Response
Description	Number of participants with an objective response-based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR defined as the disappearance of all target lesions. PR defined as greater than or equal to (≥) 30 percent (%) decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Time Frame	Baseline, Day 21 of every even-numbered cycle up to 15 Months

Outcome Measure Data

Analysis Population Description

Efficacy: all participants enrolled in the study who received at least 1 dose of study medication. N=number of participants with measurable disease at baseline.

Arm/Group Title	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU	Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU
Arm/Group Description	Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Sunitinib: 37.5 mg oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m^2) on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Measure Participants	23	10
Number [Participants]	6 25%	3 30%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU, Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Objective Response Rate (ORR) (percent)
	Estimated Value	27.3
	Confidence Interval	(2-Sided) 95%; 13.3 to 45.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

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 any cause, whichever occurrs first. DR calculated as (Months) equals (the end date for DR minus first subsequent confirmed CR or PR plus 1) divided by 30.
Time Frame	Baseline up to Month 15

Outcome Measure Data

Analysis Population Description

Efficacy; N=number of participants with objective response.

Arm/Group Title	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU	Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU
Arm/Group Description	Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Sunitinib: 37.5 mg oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m^2) on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Measure Participants	6	3
Mean (Standard Deviation) [Months]	4.17 (2.28)	4.13 (0.73)

11. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	Median time (50%) from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. PFS calculated as (Months) equals (first event date minus first dose date plus 1) divided by 30.
Time Frame	Baseline up to Month 15

Outcome Measure Data

Analysis Population Description

Efficacy

Arm/Group Title	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU	Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU
Arm/Group Description	Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Sunitinib: 37.5 mg oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m^2) on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Measure Participants	24	10
Median (95% Confidence Interval) [Months]	5.2	6.2

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an adverse event (AE) and a serious adverse event (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) in Combination With Cisplatin and 5-FU		Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU
Arm/Group Description	Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.		Sunitinib: 37.5 mg oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m^2) on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
All Cause Mortality
	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU		Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU		Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/24 (29.2%)		5/10 (50%)
Blood and lymphatic system disorders
Anaemia	0/24 (0%)		1/10 (10%)
Febrile neutropenia	1/24 (4.2%)		2/10 (20%)
Neutropenia	2/24 (8.3%)		0/10 (0%)
Cardiac disorders
Myocardial ischaemia	1/24 (4.2%)		0/10 (0%)
Gastrointestinal disorders
Diarrhoea	0/24 (0%)		1/10 (10%)
Gastrointestinal perforation	1/24 (4.2%)		0/10 (0%)
Oesophagitis	0/24 (0%)		1/10 (10%)
Vomiting	0/24 (0%)		1/10 (10%)
General disorders
Device occlusion	0/24 (0%)		1/10 (10%)
Disease progression	0/24 (0%)		1/10 (10%)
Fatigue	0/24 (0%)		1/10 (10%)
Mucosal inflammation	0/24 (0%)		3/10 (30%)
Pyrexia	1/24 (4.2%)		0/10 (0%)
Renal and urinary disorders
Renal failure acute	1/24 (4.2%)		0/10 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	2/24 (8.3%)		0/10 (0%)
Skin and subcutaneous tissue disorders
Rash	0/24 (0%)		1/10 (10%)
Other (Not Including Serious) Adverse Events
	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU		Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/24 (100%)		10/10 (100%)
Blood and lymphatic system disorders
Anaemia	12/24 (50%)		6/10 (60%)
Leukopenia	2/24 (8.3%)		0/10 (0%)
Lymphopenia	1/24 (4.2%)		0/10 (0%)
Neutropenia	21/24 (87.5%)		10/10 (100%)
Thrombocytopenia	6/24 (25%)		5/10 (50%)
Ear and labyrinth disorders
Tinnitus	1/24 (4.2%)		0/10 (0%)
Eye disorders
Conjunctival haemorrhage	2/24 (8.3%)		0/10 (0%)
Conjunctivitis	0/24 (0%)		1/10 (10%)
Eyelid oedema	1/24 (4.2%)		0/10 (0%)
Gastrointestinal disorders
Abdominal pain	6/24 (25%)		3/10 (30%)
Abdominal pain upper	6/24 (25%)		4/10 (40%)
Aerophagia	2/24 (8.3%)		0/10 (0%)
Anal pruritus	1/24 (4.2%)		0/10 (0%)
Cheilitis	2/24 (8.3%)		2/10 (20%)
Constipation	5/24 (20.8%)		4/10 (40%)
Diarrhoea	9/24 (37.5%)		4/10 (40%)
Dry mouth	1/24 (4.2%)		0/10 (0%)
Dyspepsia	2/24 (8.3%)		1/10 (10%)
Dysphagia	2/24 (8.3%)		2/10 (20%)
Flatulence	1/24 (4.2%)		0/10 (0%)
Gastrooesophageal reflux disease	4/24 (16.7%)		1/10 (10%)
Gingival bleeding	0/24 (0%)		1/10 (10%)
Haemorrhoids	0/24 (0%)		1/10 (10%)
Nausea	14/24 (58.3%)		4/10 (40%)
Odynophagia	0/24 (0%)		1/10 (10%)
Oesophagitis	1/24 (4.2%)		1/10 (10%)
Rectal haemorrhage	0/24 (0%)		1/10 (10%)
Stomatitis	1/24 (4.2%)		1/10 (10%)
Toothache	2/24 (8.3%)		0/10 (0%)
Vomiting	13/24 (54.2%)		9/10 (90%)
General disorders
Asthenia	19/24 (79.2%)		7/10 (70%)
Chest pain	1/24 (4.2%)		0/10 (0%)
Disease progression	0/24 (0%)		1/10 (10%)
Fatigue	1/24 (4.2%)		5/10 (50%)
Medical device complication	0/24 (0%)		1/10 (10%)
Mucosal inflammation	19/24 (79.2%)		8/10 (80%)
Oedema	0/24 (0%)		1/10 (10%)
Oedema peripheral	2/24 (8.3%)		2/10 (20%)
Pain	3/24 (12.5%)		1/10 (10%)
Pyrexia	3/24 (12.5%)		4/10 (40%)
Hepatobiliary disorders
Jaundice	0/24 (0%)		1/10 (10%)
Portal vein thrombosis	0/24 (0%)		1/10 (10%)
Infections and infestations
Bacteraemia	1/24 (4.2%)		0/10 (0%)
Bronchitis	1/24 (4.2%)		0/10 (0%)
Cellulitis	1/24 (4.2%)		0/10 (0%)
Device related infection	1/24 (4.2%)		0/10 (0%)
Nasopharyngitis	2/24 (8.3%)		0/10 (0%)
Oral candidiasis	0/24 (0%)		1/10 (10%)
Oral herpes	1/24 (4.2%)		0/10 (0%)
Pneumonia	0/24 (0%)		1/10 (10%)
Respiratory tract infection	0/24 (0%)		1/10 (10%)
Skin infection	2/24 (8.3%)		0/10 (0%)
Tooth infection	1/24 (4.2%)		0/10 (0%)
Urinary tract infection	2/24 (8.3%)		1/10 (10%)
Investigations
Blood alkaline phosphatase increased	2/24 (8.3%)		0/10 (0%)
Blood creatinine increased	1/24 (4.2%)		0/10 (0%)
Gamma-glutamyltransferase increased	2/24 (8.3%)		0/10 (0%)
Weight decreased	1/24 (4.2%)		2/10 (20%)
Metabolism and nutrition disorders
Cachexia	0/24 (0%)		1/10 (10%)
Decreased appetite	12/24 (50%)		7/10 (70%)
Hyperglycaemia	1/24 (4.2%)		0/10 (0%)
Hyperkalaemia	1/24 (4.2%)		0/10 (0%)
Hyperuricaemia	1/24 (4.2%)		0/10 (0%)
Hypokalaemia	0/24 (0%)		1/10 (10%)
Hyponatraemia	0/24 (0%)		1/10 (10%)
Musculoskeletal and connective tissue disorders
Back pain	3/24 (12.5%)		1/10 (10%)
Bone pain	1/24 (4.2%)		0/10 (0%)
Musculoskeletal chest pain	2/24 (8.3%)		1/10 (10%)
Musculoskeletal pain	3/24 (12.5%)		1/10 (10%)
Pain in extremity	1/24 (4.2%)		2/10 (20%)
Nervous system disorders
Dizziness	5/24 (20.8%)		2/10 (20%)
Dysgeusia	2/24 (8.3%)		1/10 (10%)
Headache	3/24 (12.5%)		1/10 (10%)
Neuropathy peripheral	1/24 (4.2%)		1/10 (10%)
Neurotoxicity	4/24 (16.7%)		0/10 (0%)
Paraesthesia	1/24 (4.2%)		2/10 (20%)
Peripheral sensory neuropathy	0/24 (0%)		2/10 (20%)
Psychiatric disorders
Anxiety	1/24 (4.2%)		0/10 (0%)
Insomnia	2/24 (8.3%)		2/10 (20%)
Renal and urinary disorders
Renal artery thrombosis	1/24 (4.2%)		0/10 (0%)
Renal pain	1/24 (4.2%)		0/10 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	3/24 (12.5%)		1/10 (10%)
Dysphonia	0/24 (0%)		1/10 (10%)
Dyspnoea	2/24 (8.3%)		1/10 (10%)
Epistaxis	6/24 (25%)		2/10 (20%)
Hiccups	1/24 (4.2%)		0/10 (0%)
Nasal inflammation	2/24 (8.3%)		0/10 (0%)
Pulmonary embolism	2/24 (8.3%)		0/10 (0%)
Skin and subcutaneous tissue disorders
Alopecia	0/24 (0%)		3/10 (30%)
Erythema	2/24 (8.3%)		0/10 (0%)
Palmar-plantar erythrodysaesthesia syndrome	1/24 (4.2%)		0/10 (0%)
Rash	1/24 (4.2%)		2/10 (20%)
Skin depigmentation	0/24 (0%)		1/10 (10%)
Vascular disorders
Aortic thrombosis	1/24 (4.2%)		0/10 (0%)
Deep vein thrombosis	1/24 (4.2%)		0/10 (0%)
Hypertension	3/24 (12.5%)		1/10 (10%)
Iliac artery thrombosis	1/24 (4.2%)		0/10 (0%)
Jugular vein thrombosis	2/24 (8.3%)		0/10 (0%)
Pallor	0/24 (0%)		1/10 (10%)
Phlebitis	1/24 (4.2%)		0/10 (0%)
Vena cava thrombosis	1/24 (4.2%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

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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.