Randomized Study Of Sunitinib Plus FOLFOX Versus Bevacizumab Plus FOLFOX In Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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This study will compare the safety and efficacy of sunitinib in combination with FOLFOX versus bevacizumab in combination with FOLFOX for the treatment of patients with metastatic colorectal cancer who have not been treated before.

Detailed Description
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The study was terminated on April 26, 2010 due to lack of efficacy, as determined during the interim analysis of data in April 2010, showing that the study did not meet its primary endpoint to demonstrate a statistically significant improvement in PFS. The decision to terminate the trial was not based on any safety concerns.

Official Title
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A Randomized, Phase 2B Study Of Sunitinib Plus Oxaliplatin, 5-Fluorouracil And Leucovorin (FOLFOX) Versus Bevacizumab Plus FOLFOX As First-Line Treatment In Patients With Metastatic Colorectal Cancer

Conditions
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Colorectal Neoplasms

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adenocarcinoma of the colon or rectum with locally advanced or metastatic disease Evidence of measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Eastern Cooperative Oncology Group (ECOG) 0 or 1 Exclusion Criteria: Previous treatment with Sutent, Avastin, or any other systemic therapy for locally advanced or metastatic colorectal cancer Less than 6 months since completion of adjuvant chemotherapy to documentation of recurrent disease History of cardiac disease Brain mets

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Treatment arm A - sunitinib plus mFOLFOX6 | Drug: sunitinib<br>* Sunitinib: 37.5 mg/day, oral, administered on an outpatient basis for 4 weeks on, 2 weeks off (Schedule 4/2).<br>* Other names: Sutent, SU011248;Drug: mFOLFOX6<br>* FOLFOX will be administered every 2 weeks, using the modified FOLFOX6 (mFOLFOX6) regimen, consisting of: - oxaliplatin 85 mg/ m^2 + leucovorin 400 mg/ m^2 (or 200 mg/ m^2 levo-leucovorin) as a 2-hr IV infusion followed by 5-fluorouracil 400 mg/ m^2 IV bolus on day 1 and 5-fluorouracil 2400 mg/ m^2 IV infusion over 46 hours on Days 1 and 2 of each 2 week cycle<br>|
| Active Comparator: B<br>Treatment arm B - bevacizumab plus mFOLFOX6 | Drug: bevacizumab<br>* Bevacizumab: 5 mg/kg, IV infusion, every 2 weeks.<br>* Other names: Avastin;Drug: mFOLFOX6<br>* FOLFOX will be administered every 2 weeks, using the modified FOLFOX6 (mFOLFOX6) regimen, consisting of: - oxaliplatin 85 mg/ m^2 + leucovorin 400 mg/ m^2 (or 200 mg/ m^2 levo-leucovorin) as a 2-hr IV infusion followed by 5-fluorouracil 400 mg/ m^2 IV bolus on day 1 and 5-fluorouracil 2400 mg/ m^2 IV infusion over 46 hours on Days 1 and 2 of each 2 week cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was Death). | Baseline, at every 8-week intervals for 18 months then every 12 weeks thereafter until disease progression (up to Week 115) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Time in weeks from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 7. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death). | Baseline, at every 8-week intervals for 18 months, and then every 12 weeks thereafter up to every 2 months until death (up to Week 115) | 
| One Year Survival Probability | One year survival probability was defined as the probability of survival at one year after the first dose of study treatment. | Baseline, at every 8-week intervals for 18 months, and then every 12 weeks thereafter up to every 2 months until death (up to 1 year) | 
| Two Year Survival Probability | Two year survival probability was defined as the probability of survival at two years after the first dose of study treatment. | Baseline, at every 8-week intervals for 18 months, and then every 12 weeks thereafter up to every 2 months until death (up to 2 years) | 
| Percentage of Participants With Objective Response (OR) | Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed response were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and/or non target). PR were those with at least 30 percent decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent. | Baseline until disease progression or discontinuation of the study, at every 8-week intervals for 18 months, and then every 12 weeks thereafter up to Week 115 | 
| Duration of Response (DR) | Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response. | Baseline until disease progression or discontinuation of the study, at every 8-week intervals for 18 months, and then every 12 weeks thereafter up to Week 115 | 
| Change From Baseline in Functional Assessment of Cancer Treatment - Colorectal (FACT-C) Score | FACT-C used for assessment of health-related quality of life (QoL) in participants with cancer. It consists of 36 items, summarized to 5 subscales:physical well-being (PWB) (7 items), functional well-being (FWB) (7 items), social/family well-being (SWB) (7 items); all 3 subscales range from 0 to 28, emotional well-being (EWB) (6 items) range from 0 to 24, colorectal cancer subscale (9 items) range from 0 to 36; higher subscale score=better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score range: 0 to 144. High scale score represents a better QoL. | Baseline [Day (D) 1 of Cycle (C) 1] then every 3 cycles thereafter and at the end of treatment (EOT) or withdrawal visit (up to Week 115) | 
| Change From Baseline in Functional Assessment of Cancer Treatment - Gynecologic Oncology Group Oxaliplatin-Specific Neurotoxicity (FACT&GOG-Ntx) Score | FACT&GOG-Ntx has a 13-item, treatment-specific subscale for patients with neurotoxicity. It is the sum of the PWB (7 items), FWB (7 items), SWB (7 items) and EWB (6 items) subscales plus a 13 item neurotoxicity subscale. Subscale score ranges from 0 to 28 for PWB, FWB, SWB, 0 to 24 for EWB and 0 to 52 for neurotoxicity subscale. Total possible score range is 0 to 160. Higher scores indicates better QoL, fewer disease symptoms, and/or fewer side effects of treatment and lower scores indicate worse QoL and a greater impact of disease symptoms and/or side effects. | Baseline (D1 of C1) then every 3 cycles thereafter and at the EOT or withdrawal visit (up to 115 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic colorectal cancer sunitinib (Sutent) bevacizumab (Avastin) randomized study