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

• Plasma Concentration of Sunitinib [ Time Frame: Cycle 1 Day 14 and Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  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.
• Plasma Concentration of Sunitinib Active Metabolite (SU012662) [ Time Frame: Cycle 1 Day 14 and Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  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.
• Plasma Concentration of the Total Drug (Sunitinib Plus SU012662) [ Time Frame: Cycle 1 Day 14 and Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  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.
• Best Overall Response Based on Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to the last subject completed Cycle 24 or individual study discontinuation ] [ Designated as safety issue: No ]
  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.
• Duration of Response (DR) [ Time Frame: Up to 733 days (the last subject study discontinuation) ] [ Designated as safety issue: No ]
  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.
• Progression-Free Survival (PFS) [ Time Frame: Up to 733 days (the last subject study discontinuation) ] [ Designated as safety issue: No ]
  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.
• Sunitinib Relative Dose Intensity in the Treatment Arm A [ Time Frame: Up to 733 days (the last subject study discontinuation in the Treatment Arm A) ] [ Designated as safety issue: No ]
  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.
• Sunitinib Relative Dose Intensity in the Treatment Arm B [ Time Frame: Up to 384 days (the last subject study discontinuation in the Treatment Arm B) ] [ Designated as safety issue: No ]
  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.

• Relative dose intensity [ Time Frame: 01-Dec-2009 ] [ Designated as safety issue: No ]
• Progression-Free Survival (PFS) [ Time Frame: 01-Dec-2009 ] [ Designated as safety issue: No ]
• Duration of response (DR) [ Time Frame: 01-Dec-2009 ] [ Designated as safety issue: No ]
• Objective tumor response (confirmed complete and partial response) [ Time Frame: 01-Dec-2009 ] [ Designated as safety issue: No ]
• Pharmacokinetics of sunitinib and its active metabolite, SU012662 [ Time Frame: 01-Dec-2009 ] [ Designated as safety issue: No ]

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.

• Drug: sunitinib + mFOLFOX6
  37.5 mg/day, oral, administered on an outpatient basis for 4 weeks on, 2 weeks off (Schedule 4/2)
• Drug: sunitinib + mFOLFOX6
  50 mg/day, oral, administered on an outpatient basis for 2 weeks on, 2 weeks off (Schedule 2/2)

• Experimental: A
  Intervention: Drug: sunitinib + mFOLFOX6
• Experimental: B
  Intervention: Drug: sunitinib + mFOLFOX6

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.