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

Study Overview
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Brief Summary
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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.

Official Title
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Phase I Study Of Sunitinib In Combination With Oxaliplatin, L-Leucovorin, And 5-Fluorouracil In Patients With Metastatic Colorectal Cancer

Conditions
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Colorectal Neoplasms

Intervention / Treatment
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* Drug: sunitinib + mFOLFOX6
* Drug: sunitinib + mFOLFOX6


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: sunitinib + mFOLFOX6<br>* 37.5 mg/day, oral, administered on an outpatient basis for 4 weeks on, 2 weeks off (Schedule 4/2)<br>|
| Experimental: B<br> | Drug: sunitinib + mFOLFOX6<br>* 50 mg/day, oral, administered on an outpatient basis for 2 weeks on, 2 weeks off (Schedule 2/2)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | 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. | Up to 733 days (the last subject study discontinuation) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Concentration of Sunitinib | 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. | Cycle 1 Day 14 and Cycle 2 Day 1 | 
| Plasma Concentration of Sunitinib Active Metabolite (SU012662) | 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. | Cycle 1 Day 14 and Cycle 2 Day 1 | 
| Plasma Concentration of the Total Drug (Sunitinib Plus SU012662) | 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. | Cycle 1 Day 14 and Cycle 2 Day 1 | 
| Best Overall Response Based on Response Evaluation Criteria in Solid Tumors (RECIST) | 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. | Up to the last subject completed Cycle 24 or individual study discontinuation | 
| Duration of Response (DR) | 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. | Up to 733 days (the last subject study discontinuation) | 
| Progression-Free Survival (PFS) | 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. | Up to 733 days (the last subject study discontinuation) | 
| Sunitinib Relative Dose Intensity 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; Periodn: Cycle (n-1)*3+1 to n*3. | Up to 733 days (the last subject study discontinuation in the Treatment Arm A) | 
| Sunitinib Relative Dose Intensity 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, Periodn: Cycle (n-1)*2+1 to n*2. | Up to 384 days (the last subject study discontinuation in the Treatment Arm B) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, CRC, SU011248, Sunitinib, FOLFOX, Colorectal cancer, metastatic carcinoma of the colon or rectum