Study Of Sunitinib In Combination With Folfox In Patients With Colorectal Cancer

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00631410
• Collaborator: (none)
• Enrollment: 12
• Locations: 3
• Arms: 2
• Duration (Months): 26
• Patients Per Site: 4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

To assess the safety and tolerability of sunitinib when administered in combination with modified FOLFOX6 in Japanese patients with metastatic colorectal cancer in the first-line treatment setting.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Neoplasms	Drug: sunitinib + mFOLFOX6; Drug: sunitinib + mFOLFOX6	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I Study Of Sunitinib In Combination With Oxaliplatin, L-Leucovorin, And 5-Fluorouracil In Patients With Metastatic Colorectal Cancer
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A	Drug: sunitinib + mFOLFOX6; 37.5 mg/day, oral, administered on an outpatient basis for 4 weeks on, 2 weeks off (Schedule 4/2)
Experimental: B	Drug: sunitinib + mFOLFOX6; 50 mg/day, oral, administered on an outpatient basis for 2 weeks on, 2 weeks off (Schedule 2/2)

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events [Up to 733 days (the last subject study discontinuation)]

   Number of participants with any adverse events, adverse events graded as Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 3 or higher , serious adverse events, adverse events resulted in discontinuation, treatment interruption, or dose reduction.

Secondary Outcome Measures

1. Plasma Concentration of Sunitinib [Cycle 1 Day 14 and Cycle 2 Day 1]

   Concentrations after administration of sunitinib alone (Day 14 of Cycle 1) and those after administration of sunitinib in combination with mFOLFOX6 (Day 1 of Cycle 2) were evaluated.

2. Plasma Concentration of Sunitinib Active Metabolite (SU012662) [Cycle 1 Day 14 and Cycle 2 Day 1]

   Concentrations after administration of sunitinib alone (Day 14 of Cycle 1) and those after administration of sunitinib in combination with mFOLFOX6 (Day 1 of Cycle 2) were evaluated.

3. Plasma Concentration of the Total Drug (Sunitinib Plus SU012662) [Cycle 1 Day 14 and Cycle 2 Day 1]

   Concentrations after administration of sunitinib alone (Day 14 of Cycle 1) and those after administration of sunitinib in combination with mFOLFOX6 (Day 1 of Cycle 2) were evaluated.

4. Best Overall Response Based on Response Evaluation Criteria in Solid Tumors (RECIST) [Up to the last subject completed Cycle 24 or individual study discontinuation]

   Complete response (CR): 2 or more sequential occasions of documented objective disappearance of all target lesions at a minimum of 4 weeks apart; partial response (PR): 2 or more occasions of >=30% decrease in the sum of the longest diameter (LD) of the target lesions from baseline at a minimum of 4 weeks apart; stable disease (SD): at least 1 objective status of stable/no response at least 6 weeks after enrollment; progressive disease (PD): Objective status of progression within 12 weeks of enrollment, not qualifying as CR, PR or Stable; Indeterminate: no other response category applies.

5. Duration of Response (DR) [Up to 733 days (the last subject study discontinuation)]

   Duration of response is defined as the duration from the date of first documentation of complete response (CR) or partial response (PR) to date of first documentation of objective progression based on the investigator's assessment.

6. Progression-Free Survival (PFS) [Up to 733 days (the last subject study discontinuation)]

   Progression-free survival is defined as the time from date of enrolment to date of first documentation of progression based on investigator's assessment or death due to any cause.

7. Sunitinib Relative Dose Intensity in the Treatment Arm A [Up to 733 days (the last subject study discontinuation in the Treatment Arm A)]

   Relative dose intensity is defined as percentage of total dose administered over total dose assigned through assessment period. Period 1: Cycle 1 to 3; Period 2: Cycle 4 to 6; Period"n": Cycle (n-1)*3+1 to n*3.

8. Sunitinib Relative Dose Intensity in the Treatment Arm B [Up to 384 days (the last subject study discontinuation in the Treatment Arm B)]

   Relative dose intensity is defined as percentage of total dose administered over total dose assigned through assessment period. Period 1: Cycle 1 to 2; Period 2: Cycle 3 to 4, Period"n": Cycle (n-1)*2+1 to n*2.

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 adenocarcinoma of the colon or rectum with documented locally advanced or metastatic disease.

• Evidence of unidimensionally measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST).

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion Criteria:

• Prior treatment with systemic therapy for locally advanced or metastatic colorectal cancer.

• Prior surgery or investigational agent within 4 weeks prior to study entry.

• Pregnancy or breastfeeding. All female patients of reproductive potential must have a negative pregnancy test (serum or urine) prior to the start of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Kashiwa	Chiba	Japan
2	Pfizer Investigational Site	Suntougun	Shizuoka	Japan
3	Pfizer Investigational Site	Chuo-ku	Tokyo	Japan

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.

• ClinicalTrials.gov Identifier: NCT00631410
• Other Study ID Numbers: A6181148
• First Posted: Mar 7, 2008
• Last Update Posted: Mar 16, 2011
• Last Verified: Mar 1, 2011

• Keywords provided by , ,: Phase 1; CRC; SU011248; Sunitinib; FOLFOX; Colorectal cancer; metastatic carcinoma of the colon or rectum
• Additional relevant MeSH terms: Colorectal Neoplasms; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Treatment Arm A 37.5 mg/Day (4/2)	Treatment Arm B 50 mg/Day (2/2)
Arm/Group Description	Sunitinib was administered orally in a 4 weeks on, 2 weeks off intermittent dosing regimen, at a starting dose of 37.5 mg/day (37.5 mg/day in Schedule 4/2). A combination chemotherapy of fluorouracil, calcium folinate and oxaliplatin (FOLFOX) was administered on an every-2-week cycle using the mFOLFOX6 regimen consisting of oxaliplatin 85 mg/meter^2 and l-leucovorin 200 mg/meter^2 as a 2-hour intravenous infusion followed by an intravenous bolus of fluorouracil 400 mg/meter^2 and a 46-hour intravenous infusion of fluorouracil 2,400 mg/meter^2 on Days 1 and 2 of each cycle.	Sunitinib was administered orally in a 2 weeks on, 2 weeks off intermittent dosing regimen, at a starting dose of 50 mg/day (50 mg/day in Schedule 2/2). A combination chemotherapy of fluorouracil, calcium folinate and oxaliplatin (FOLFOX) was administered on an every-2-week cycle using the mFOLFOX6 regimen consisting of oxaliplatin 85 mg/meter^2 and l-leucovorin 200 mg/meter^2 as a 2-hour intravenous infusion followed by an intravenous bolus of fluorouracil 400 mg/meter^2 and a 46-hour intravenous infusion of fluorouracil 2,400 mg/meter^2 on Days 1 and 2 of each cycle.
Period Title: Overall Study
STARTED	6	6
COMPLETED	0	0
NOT COMPLETED	6	6

Baseline Characteristics

Arm/Group Title	Treatment Arm A 37.5 mg/Day (4/2)	Treatment Arm B 50 mg/Day (2/2)	Total
Arm/Group Description	Sunitinib was administered orally in a 4 weeks on, 2 weeks off intermittent dosing regimen, at a starting dose of 37.5 mg/day (37.5 mg/day in Schedule 4/2). FOLFOX was administered on an every-2-week cycle using the mFOLFOX6 regimen consisting of oxaliplatin 85 mg/meter^2 and l-leucovorin 200 mg/meter^2 as a 2-hour intravenous infusion followed by an intravenous bolus of fluorouracil 400 mg/meter^2 and a 46-hour intravenous infusion of fluorouracil 2,400 mg/meter^2 on Days 1 and 2 of each cycle.	Sunitinib was administered orally in a 2 weeks on, 2 weeks off intermittent dosing regimen, at a starting dose of 50 mg/day (50 mg/day in Schedule 2/2). FOLFOX was administered on an every-2-week cycle using the mFOLFOX6 regimen consisting of oxaliplatin 85 mg/meter^2 and l-leucovorin 200 mg/meter^2 as a 2-hour intravenous infusion followed by an intravenous bolus of fluorouracil 400 mg/meter^2 and a 46-hour intravenous infusion of fluorouracil 2,400 mg/meter^2 on Days 1 and 2 of each cycle.	Total of all reporting groups
Overall Participants	6	6	12
Age, Customized (participants) [Number]
20-44 years	0 0%	0 0%	0 0%
45-64 years	4 66.7%	3 50%	7 58.3%
>=65 years	2 33.3%	3 50%	5 41.7%
Sex: Female, Male (Count of Participants)
Female	1 16.7%	1 16.7%	2 16.7%
Male	5 83.3%	5 83.3%	10 83.3%
Eastern Cooperative Oncology Group (ECOG) Performance Status (participants) [Number]
Score 0	5 83.3%	6 100%	11 91.7%
Score 1	1 16.7%	0 0%	1 8.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events
Description	Number of participants with any adverse events, adverse events graded as Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 3 or higher , serious adverse events, adverse events resulted in discontinuation, treatment interruption, or dose reduction.
Time Frame	Up to 733 days (the last subject study discontinuation)

Outcome Measure Data

Analysis Population Description

All subjects who received at least 1 dose of the study drug.

Arm/Group Title	Treatment Arm A 37.5 mg/Day (4/2)	Treatment Arm B 50 mg/Day (2/2)
Arm/Group Description	Sunitinib was administered orally in a 4 weeks on, 2 weeks off intermittent dosing regimen, at a starting dose of 37.5 mg/day (37.5 mg/day in Schedule 4/2). FOLFOX was administered on an every-2-week cycle using the mFOLFOX6 regimen consisting of oxaliplatin 85 mg/meter^2 and ℓ-leucovorin 200 mg/meter^2 as a 2-hour intravenous infusion followed by an intravenous bolus of fluorouracil 400 mg/meter^2 and a 46-hour intravenous infusion of fluorouracil 2,400 mg/meter^2 on Days 1 and 2 of each cycle.	Sunitinib was administered orally in a 2 weeks on, 2 weeks off intermittent dosing regimen, at a starting dose of 50 mg/day (50 mg/day in Schedule 2/2). FOLFOX was administered on an every-2-week cycle using the mFOLFOX6 regimen consisting of oxaliplatin 85 mg/meter^2 and l-leucovorin 200 mg/meter^2 as a 2-hour intravenous infusion followed by an intravenous bolus of fluorouracil 400 mg/meter^2 and a 46-hour intravenous infusion of fluorouracil 2,400 mg/meter^2 on Days 1 and 2 of each cycle.
Measure Participants	6	6
Any adverse events	6 100%	6 100%
Any serious adverse evets	2 33.3%	4 66.7%
Any Grade-3 or -4 adverse evets	6 100%	6 100%
Any Grade-5 adverse events (= death)	0 0%	0 0%
Discontinuation due to adverse events	1 16.7%	3 50%
Sunitinib interruption due to adverse events	6 100%	6 100%
mFOLFOX6 interruption due to adverse events	6 100%	6 100%
Sunitinib dose reduction due to adverse events	1 16.7%	1 16.7%
mFOLFOX6 dose reduction due to adverse events	2 33.3%	4 66.7%

2. Secondary Outcome

Title	Plasma Concentration of Sunitinib
Description	Concentrations after administration of sunitinib alone (Day 14 of Cycle 1) and those after administration of sunitinib in combination with mFOLFOX6 (Day 1 of Cycle 2) were evaluated.
Time Frame	Cycle 1 Day 14 and Cycle 2 Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis population consisted of subjects with at least 1 plasma drug concentration measurement in the Treatment Arm B.

Arm/Group Title	Treatment Arm B 50 mg/Day (2/2)
Arm/Group Description	Sunitinib was administered orally in a 2 weeks on, 2 weeks off intermittent dosing regimen, at a starting dose of 50 mg/day (50 mg/day in Schedule 2/2). FOLFOX was administered on an every-2-week cycle using the mFOLFOX6 regimen consisting of oxaliplatin 85 mg/meter^2 and l-leucovorin 200 mg/meter^2 as a 2-hour intravenous infusion followed by an intravenous bolus of fluorouracil 400 mg/meter^2 and a 46-hour intravenous infusion of fluorouracil 2,400 mg/meter^2 on Days 1 and 2 of each cycle.
Measure Participants	4
Cycle 1 Day 14, 0 hour post dose	85.40
Cycle 1 Day 14, 2 hour post dose	86.15
Cycle 1 Day 14, 6 hour post dose	93.35
Cycle 1 Day 14, 8 hour post dose	98.50
Cycle 2 Day 1, 0 hour post dose	81.70
Cycle 2 Day 1, 2 hour post dose	87.05
Cycle 2 Day 1, 6 hour post dose	109.50
Cycle 2 Day 1, 8 hour post dose	102.00
Cycle 2 Day 1, 24 hour post dose	81.50

3. Secondary Outcome

Title	Plasma Concentration of Sunitinib Active Metabolite (SU012662)
Description	Concentrations after administration of sunitinib alone (Day 14 of Cycle 1) and those after administration of sunitinib in combination with mFOLFOX6 (Day 1 of Cycle 2) were evaluated.
Time Frame	Cycle 1 Day 14 and Cycle 2 Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis population consisted of subjects with at least 1 plasma drug concentration measurement in the Treatment Arm B.

Arm/Group Title	Treatment Arm B 50 mg/Day (2/2)
Arm/Group Description	Sunitinib was administered orally in a 2 weeks on, 2 weeks off intermittent dosing regimen, at a starting dose of 50 mg/day (50 mg/day in Schedule 2/2). FOLFOX was administered on an every-2-week cycle using the mFOLFOX6 regimen consisting of oxaliplatin 85 mg/meter^2 and l-leucovorin 200 mg/meter^2 as a 2-hour intravenous infusion followed by an intravenous bolus of fluorouracil 400 mg/meter^2 and a 46-hour intravenous infusion of fluorouracil 2,400 mg/meter^2 on Days 1 and 2 of each cycle.
Measure Participants	4
Cycle 1 Day 14, 0 hour post dose	41.75
Cycle 1 Day 14, 2 hour post dose	36.90
Cycle 1 Day 14, 6 hour post dose	43.55
Cycle 1 Day 14, 8 hour post dose	42.35
Cycle 2 Day 1, 0 hour post dose	42.65
Cycle 2 Day 1, 2 hour post dose	36.10
Cycle 2 Day 1, 6 hour post dose	46.95
Cycle 2 Day 1, 8 hour post dose	47.10
Cycle 2 Day 1, 24 hour post dose	44.85

4. Secondary Outcome

Title	Plasma Concentration of the Total Drug (Sunitinib Plus SU012662)
Description	Concentrations after administration of sunitinib alone (Day 14 of Cycle 1) and those after administration of sunitinib in combination with mFOLFOX6 (Day 1 of Cycle 2) were evaluated.
Time Frame	Cycle 1 Day 14 and Cycle 2 Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis population consisted of subjects with at least 1 plasma drug concentration measurement in the Treatment Arm B.

Arm/Group Title	Treatment Arm B 50 mg/Day (2/2)
Arm/Group Description	Sunitinib was administered orally in a 2 weeks on, 2 weeks off intermittent dosing regimen, at a starting dose of 50 mg/day (50 mg/day in Schedule 2/2). FOLFOX was administered on an every-2-week cycle using the mFOLFOX6 regimen consisting of oxaliplatin 85 mg/meter^2 and l-leucovorin 200 mg/meter^2 as a 2-hour intravenous infusion followed by an intravenous bolus of fluorouracil 400 mg/meter^2 and a 46-hour intravenous infusion of fluorouracil 2,400 mg/meter^2 on Days 1 and 2 of each cycle.
Measure Participants	4
Cycle 1 Day 14, 0 hour post dose	136.25
Cycle 1 Day 14, 2 hour post dose	123.05
Cycle 1 Day 14, 6 hour post dose	136.75
Cycle 1 Day 14, 8 hour post dose	142.35
Cycle 2 Day 1, 0 hour post dose	132.85
Cycle 2 Day 1, 2 hour post dose	122.15
Cycle 2 Day 1, 6 hour post dose	155.45
Cycle 2 Day 1, 8 hour post dose	156.60
Cycle 2 Day 1, 24 hour post dose	132.15

5. Secondary Outcome

Title	Best Overall Response Based on Response Evaluation Criteria in Solid Tumors (RECIST)
Description	Complete response (CR): 2 or more sequential occasions of documented objective disappearance of all target lesions at a minimum of 4 weeks apart; partial response (PR): 2 or more occasions of >=30% decrease in the sum of the longest diameter (LD) of the target lesions from baseline at a minimum of 4 weeks apart; stable disease (SD): at least 1 objective status of stable/no response at least 6 weeks after enrollment; progressive disease (PD): Objective status of progression within 12 weeks of enrollment, not qualifying as CR, PR or Stable; Indeterminate: no other response category applies.
Time Frame	Up to the last subject completed Cycle 24 or individual study discontinuation

Outcome Measure Data

Analysis Population Description

All enrolled subjects who 1) had a diagnosis of locally-advanced or metastatic adenocarcinoma of the colon or rectum with measurable disease at baseline; 2) had received at least one dose of the investigational product; and 3) with efficacy data available after administration of the investigational product.

Arm/Group Title	Treatment Arm A 37.5 mg/Day (4/2)	Treatment Arm B 50 mg/Day (2/2)
Arm/Group Description	Sunitinib was administered orally in a 4 weeks on, 2 weeks off intermittent dosing regimen, at a starting dose of 37.5 mg/day (37.5 mg/day in Schedule 4/2). FOLFOX was administered on an every-2-week cycle using the mFOLFOX6 regimen consisting of oxaliplatin 85 mg/meter^2 and l-leucovorin 200 mg/meter^2 as a 2-hour intravenous infusion followed by an intravenous bolus of fluorouracil 400 mg/meter^2 and a 46-hour intravenous infusion of fluorouracil 2,400 mg/meter^2 on Days 1 and 2 of each cycle.	Sunitinib was administered orally in a 2 weeks on, 2 weeks off intermittent dosing regimen, at a starting dose of 50 mg/day (50 mg/day in Schedule 2/2). FOLFOX was administered on an every-2-week cycle using the mFOLFOX6 regimen consisting of oxaliplatin 85 mg/meter^2 and l-leucovorin 200 mg/meter^2 as a 2-hour intravenous infusion followed by an intravenous bolus of fluorouracil 400 mg/meter^2 and a 46-hour intravenous infusion of fluorouracil 2,400 mg/meter^2 on Days 1 and 2 of each cycle.
Measure Participants	6	6
Complete Response (CR)	0 0%	0 0%
Partial Response (PR)	4 66.7%	4 66.7%
Stable Disease (SD)	1 16.7%	1 16.7%
Progressive Disease (PD)	1 16.7%	0 0%
Indeterminate	0 0%	1 16.7%
Objective Response (CR+PR)	4 66.7%	4 66.7%

6. Secondary Outcome

Title	Duration of Response (DR)
Description	Duration of response is defined as the duration from the date of first documentation of complete response (CR) or partial response (PR) to date of first documentation of objective progression based on the investigator's assessment.
Time Frame	Up to 733 days (the last subject study discontinuation)

Outcome Measure Data

Analysis Population Description

Summary statistics were not calculated due to a small number of subjects.

Arm/Group Title	Treatment Arm A 37.5 mg/Day (4/2)	Treatment Arm B 50 mg/Day (2/2)
Arm/Group Description	Sunitinib was administered orally in a 4 weeks on, 2 weeks off intermittent dosing regimen, at a starting dose of 37.5 mg/day (37.5 mg/day in Schedule 4/2). FOLFOX was administered on an every-2-week cycle using the mFOLFOX6 regimen consisting of oxaliplatin 85 mg/meter^2 and l-leucovorin 200 mg/meter^2 as a 2-hour intravenous infusion followed by an intravenous bolus of fluorouracil 400 mg/meter^2 and a 46-hour intravenous infusion of fluorouracil 2,400 mg/meter^2 on Days 1 and 2 of each cycle.	Sunitinib was administered orally in a 2 weeks on, 2 weeks off intermittent dosing regimen, at a starting dose of 50 mg/day (50 mg/day in Schedule 2/2). FOLFOX was administered on an every-2-week cycle using the mFOLFOX6 regimen consisting of oxaliplatin 85 mg/meter^2 and l-leucovorin 200 mg/meter^2 as a 2-hour intravenous infusion followed by an intravenous bolus of fluorouracil 400 mg/meter^2 and a 46-hour intravenous infusion of fluorouracil 2,400 mg/meter^2 on Days 1 and 2 of each cycle.
Measure Participants	0	0

7. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	Progression-free survival is defined as the time from date of enrolment to date of first documentation of progression based on investigator's assessment or death due to any cause.
Time Frame	Up to 733 days (the last subject study discontinuation)

Outcome Measure Data

Analysis Population Description

Summary statistics were not calculated due to a small number of subjects.

Arm/Group Title	Treatment Arm A 37.5 mg/Day (4/2)	Treatment Arm B 50 mg/Day (2/2)
Arm/Group Description	Sunitinib was administered orally in a 4 weeks on, 2 weeks off intermittent dosing regimen, at a starting dose of 37.5 mg/day (37.5 mg/day in Schedule 4/2). FOLFOX was administered on an every-2-week cycle using the mFOLFOX6 regimen consisting of oxaliplatin 85 mg/meter^2 and l-leucovorin 200 mg/meter^2 as a 2-hour intravenous infusion followed by an intravenous bolus of fluorouracil 400 mg/meter^2 and a 46-hour intravenous infusion of fluorouracil 2,400 mg/meter^2 on Days 1 and 2 of each cycle.	Sunitinib was administered orally in a 2 weeks on, 2 weeks off intermittent dosing regimen, at a starting dose of 50 mg/day (50 mg/day in Schedule 2/2). FOLFOX was administered on an every-2-week cycle using the mFOLFOX6 regimen consisting of oxaliplatin 85 mg/meter^2 and l-leucovorin 200 mg/meter^2 as a 2-hour intravenous infusion followed by an intravenous bolus of fluorouracil 400 mg/meter^2 and a 46-hour intravenous infusion of fluorouracil 2,400 mg/meter^2 on Days 1 and 2 of each cycle.
Measure Participants	0	0

8. Secondary Outcome

Title	Sunitinib Relative Dose Intensity in the Treatment Arm A
Description	Relative dose intensity is defined as percentage of total dose administered over total dose assigned through assessment period. Period 1: Cycle 1 to 3; Period 2: Cycle 4 to 6; Period"n": Cycle (n-1)*3+1 to n*3.
Time Frame	Up to 733 days (the last subject study discontinuation in the Treatment Arm A)

Outcome Measure Data

Analysis Population Description

All subjects who received at least 1 dose of the study drug. n = number of subjects assessed for relative dose intensity in the given period.

Arm/Group Title	Treatment Arm A 37.5 mg/Day (4/2)
Arm/Group Description	Sunitinib was administered orally in a 4 weeks on, 2 weeks off intermittent dosing regimen, at a starting dose of 37.5 mg/day (37.5 mg/day in Schedule 4/2). FOLFOX was administered on an every-2-week cycle using the mFOLFOX6 regimen consisting of oxaliplatin 85 mg/meter^2 and ℓ-leucovorin 200 mg/meter^2 as a 2-hour intravenous infusion followed by an intravenous bolus of fluorouracil 400 mg/meter^2 and a 46-hour intravenous infusion of fluorouracil 2,400 mg/meter^2 on Days 1 and 2 of each cycle.
Measure Participants	6
Period 1 (n=6)	57.1 (9.3)
Period 2 (n=5)	72.4 (18.5)
Period 3 (n=5)	64.3 (21.1)
Period 4 (n=4)	53.6 (15.4)
Period 5 (n=3)	42.9 (16.5)
Period 6 (n=2)	50.0 (0.0)
Period 7 (n=2)	40.5 (37.0)
Period 8 (n=1)	50.0 (0)
Period 9 (n=1)	50.0 (0)
Period 10 (n=1)	23.8 (0)
Period 11 (n=1)	33.3 (0)
Period 12 (n=1)	23.8 (0)
Period 13 (n=1)	25.0 (0)
Period 14 (n=1)	33.3 (0)
Period 15 (n=1)	23.8 (0)
Period 16 (n=1)	25.0 (0)

9. Secondary Outcome

Title	Sunitinib Relative Dose Intensity in the Treatment Arm B
Description	Relative dose intensity is defined as percentage of total dose administered over total dose assigned through assessment period. Period 1: Cycle 1 to 2; Period 2: Cycle 3 to 4, Period"n": Cycle (n-1)*2+1 to n*2.
Time Frame	Up to 384 days (the last subject study discontinuation in the Treatment Arm B)

Outcome Measure Data

Analysis Population Description

All subjects who received at least 1 dose of the study drug. n = number of subjects assessed for relative dose intensity in the given period.

Arm/Group Title	Treatment Arm B 50 mg/Day (2/2)
Arm/Group Description	Sunitinib was administered orally in a 2 weeks on, 2 weeks off intermittent dosing regimen, at a starting dose of 50 mg/day (50 mg/day in Schedule 2/2). FOLFOX was administered on an every-2-week cycle using the mFOLFOX6 regimen consisting of oxaliplatin 85 mg/meter^2 and l-leucovorin 200 mg/meter^2 as a 2-hour intravenous infusion followed by an intravenous bolus of fluorouracil 400 mg/meter^2 and a 46-hour intravenous infusion of fluorouracil 2,400 mg/meter^2 on Days 1 and 2 of each cycle.
Measure Participants	6
Period 1 (n=6)	100.0 (0)
Period 2 (n=5)	97.1 (3.9)
Period 3 (n=5)	78.6 (23.6)
Period 4 (n=5)	90.0 (13.7)
Period 5 (n=5)	82.1 (11.0)
Period 6 (n=3)	73.8 (26.8)
Period 7 (n=3)	75.0 (25.0)
Period 8 (n=3)	75.0 (25.0)
Period 9 (n=3)	73.8 (26.8)
Period 10 (n=3)	73.8 (26.8)
Period 11 (n=1)	100.0 (0)
Period 12 (n=1)	35.7 (0)

Adverse Events

Time Frame	Up to 733 days (the last subject study discontinuation)
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	Treatment Arm A 37.5 mg/Day (4/2)		Treatment Arm B 50 mg/Day (2/2)
Arm/Group Description	Sunitinib was administered orally in a 4 weeks on, 2 weeks off intermittent dosing regimen, at a starting dose of 37.5 mg/day (37.5 mg/day in Schedule 4/2). FOLFOX was administered on an every-2-week cycle using the mFOLFOX6 regimen consisting of oxaliplatin 85 mg/meter^2 and l-leucovorin 200 mg/meter^2 as a 2-hour intravenous infusion followed by an intravenous bolus of fluorouracil 400 mg/meter^2 and a 46-hour intravenous infusion of fluorouracil 2,400 mg/meter^2 on Days 1 and 2 of each cycle.		Sunitinib was administered orally in a 2 weeks on, 2 weeks off intermittent dosing regimen, at a starting dose of 50 mg/day (50 mg/day in Schedule 2/2). FOLFOX was administered on an every-2-week cycle using the mFOLFOX6 regimen consisting of oxaliplatin 85 mg/meter^2 and l-leucovorin 200 mg/meter^2 as a 2-hour intravenous infusion followed by an intravenous bolus of fluorouracil 400 mg/meter^2 and a 46-hour intravenous infusion of fluorouracil 2,400 mg/meter^2 on Days 1 and 2 of each cycle.
All Cause Mortality
	Treatment Arm A 37.5 mg/Day (4/2)		Treatment Arm B 50 mg/Day (2/2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Treatment Arm A 37.5 mg/Day (4/2)		Treatment Arm B 50 mg/Day (2/2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/6 (33.3%)		4/6 (66.7%)
Gastrointestinal disorders
Nausea	0/6 (0%)		1/6 (16.7%)
Oesophagitis	0/6 (0%)		1/6 (16.7%)
Vomiting	0/6 (0%)		1/6 (16.7%)
General disorders
Fatigue	1/6 (16.7%)		0/6 (0%)
Investigations
Neutrophil count decreased	0/6 (0%)		1/6 (16.7%)
Platelet count decreased	0/6 (0%)		1/6 (16.7%)
White blood cell count decreased	0/6 (0%)		1/6 (16.7%)
Metabolism and nutrition disorders
Anorexia	1/6 (16.7%)		2/6 (33.3%)
Dehydration	0/6 (0%)		1/6 (16.7%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/6 (16.7%)		0/6 (0%)
Nervous system disorders
Cerebral infarction	0/6 (0%)		1/6 (16.7%)
Respiratory, thoracic and mediastinal disorders
Hiccups	1/6 (16.7%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Treatment Arm A 37.5 mg/Day (4/2)		Treatment Arm B 50 mg/Day (2/2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		6/6 (100%)
Ear and labyrinth disorders
Vertigo	0/6 (0%)		1/6 (16.7%)
Endocrine disorders
Thyroid disorder	1/6 (16.7%)		0/6 (0%)
Eye disorders
Eye pruritus	0/6 (0%)		1/6 (16.7%)
Eyelid oedema	3/6 (50%)		0/6 (0%)
Gastrointestinal disorders
Abdominal pain	0/6 (0%)		1/6 (16.7%)
Abdominal pain upper	0/6 (0%)		2/6 (33.3%)
Cheilitis	1/6 (16.7%)		4/6 (66.7%)
Constipation	3/6 (50%)		3/6 (50%)
Diarrhoea	3/6 (50%)		5/6 (83.3%)
Dyspepsia	1/6 (16.7%)		2/6 (33.3%)
Gastrointestinal obstruction	1/6 (16.7%)		0/6 (0%)
Gingivitis	0/6 (0%)		3/6 (50%)
Haematochezia	0/6 (0%)		1/6 (16.7%)
Nausea	6/6 (100%)		4/6 (66.7%)
Oesophagitis	0/6 (0%)		1/6 (16.7%)
Stomatitis	2/6 (33.3%)		5/6 (83.3%)
Vomiting	5/6 (83.3%)		3/6 (50%)
General disorders
Chills	1/6 (16.7%)		1/6 (16.7%)
Fatigue	5/6 (83.3%)		5/6 (83.3%)
Oedema peripheral	1/6 (16.7%)		0/6 (0%)
Pyrexia	2/6 (33.3%)		2/6 (33.3%)
Implant site haematoma	1/6 (16.7%)		0/6 (0%)
Immune system disorders
Hypersensitivity	1/6 (16.7%)		0/6 (0%)
Infections and infestations
Herpes zoster	1/6 (16.7%)		0/6 (0%)
Nasopharyngitis	1/6 (16.7%)		1/6 (16.7%)
Pharyngitis	0/6 (0%)		1/6 (16.7%)
Injury, poisoning and procedural complications
Road traffic accident	1/6 (16.7%)		0/6 (0%)
Tooth fracture	1/6 (16.7%)		0/6 (0%)
Investigations
Alanine aminotransferase increased	1/6 (16.7%)		1/6 (16.7%)
Aspartate aminotransferase increased	2/6 (33.3%)		4/6 (66.7%)
Blood albumin decreased	2/6 (33.3%)		3/6 (50%)
Blood alkaline phosphatase increased	0/6 (0%)		2/6 (33.3%)
Blood amylase increased	2/6 (33.3%)		2/6 (33.3%)
Blood calcium decreased	1/6 (16.7%)		2/6 (33.3%)
Blood creatinine increased	2/6 (33.3%)		1/6 (16.7%)
Blood lactate dehydrogenase increased	0/6 (0%)		1/6 (16.7%)
Blood magnesium increased	1/6 (16.7%)		0/6 (0%)
Blood phosphorus decreased	0/6 (0%)		3/6 (50%)
Blood phosphorus increased	1/6 (16.7%)		0/6 (0%)
Blood potassium increased	2/6 (33.3%)		0/6 (0%)
Blood pressure increased	2/6 (33.3%)		0/6 (0%)
Blood sodium decreased	1/6 (16.7%)		0/6 (0%)
Blood thyroid stimulating hormone decreased	0/6 (0%)		1/6 (16.7%)
Blood thyroid stimulating hormone increased	0/6 (0%)		3/6 (50%)
Blood urea increased	1/6 (16.7%)		1/6 (16.7%)
Blood uric acid increased	0/6 (0%)		1/6 (16.7%)
C-reactive protein increased	1/6 (16.7%)		0/6 (0%)
Glucose urine	1/6 (16.7%)		0/6 (0%)
Haemoglobin decreased	3/6 (50%)		5/6 (83.3%)
Lymphocyte count decreased	3/6 (50%)		5/6 (83.3%)
Neutrophil count decreased	6/6 (100%)		6/6 (100%)
Platelet count decreased	6/6 (100%)		6/6 (100%)
Protein total decreased	1/6 (16.7%)		0/6 (0%)
Protein urine	1/6 (16.7%)		0/6 (0%)
Red blood cell count decreased	1/6 (16.7%)		0/6 (0%)
Weight decreased	2/6 (33.3%)		1/6 (16.7%)
White blood cell count decreased	6/6 (100%)		6/6 (100%)
Metabolism and nutrition disorders
Anorexia	5/6 (83.3%)		6/6 (100%)
Dehydration	1/6 (16.7%)		0/6 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/6 (16.7%)		0/6 (0%)
Myalgia	1/6 (16.7%)		0/6 (0%)
Nervous system disorders
Dizziness	2/6 (33.3%)		1/6 (16.7%)
Dysgeusia	1/6 (16.7%)		4/6 (66.7%)
Headache	1/6 (16.7%)		2/6 (33.3%)
Neuropathy peripheral	2/6 (33.3%)		1/6 (16.7%)
Neurotoxicity	0/6 (0%)		4/6 (66.7%)
Parosmia	1/6 (16.7%)		0/6 (0%)
Peripheral sensory neuropathy	3/6 (50%)		0/6 (0%)
Somnolence	0/6 (0%)		1/6 (16.7%)
Renal and urinary disorders
Proteinuria	0/6 (0%)		1/6 (16.7%)
Respiratory, thoracic and mediastinal disorders
Cough	0/6 (0%)		1/6 (16.7%)
Dyspnoea	0/6 (0%)		1/6 (16.7%)
Epistaxis	0/6 (0%)		3/6 (50%)
Hiccups	1/6 (16.7%)		1/6 (16.7%)
Rhinorrhoea	0/6 (0%)		2/6 (33.3%)
Skin and subcutaneous tissue disorders
Alopecia	1/6 (16.7%)		3/6 (50%)
Dry skin	1/6 (16.7%)		0/6 (0%)
Hyperhidrosis	1/6 (16.7%)		0/6 (0%)
Nail disorder	1/6 (16.7%)		0/6 (0%)
Palmar-plantar erythrodysaesthesia syndrome	4/6 (66.7%)		2/6 (33.3%)
Pigmentation disorder	0/6 (0%)		1/6 (16.7%)
Purpura	0/6 (0%)		1/6 (16.7%)
Rash	4/6 (66.7%)		3/6 (50%)
Skin discolouration	1/6 (16.7%)		0/6 (0%)
Skin erosion	1/6 (16.7%)		0/6 (0%)
Yellow skin	2/6 (33.3%)		3/6 (50%)
Vascular disorders
Hot flush	0/6 (0%)		1/6 (16.7%)
Hypertension	1/6 (16.7%)		2/6 (33.3%)

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.