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

• ClinicalTrials.gov Identifier: NCT00609622
• Recruitment Status: Terminated
• First Posted: February 7, 2008
• Results First Posted: October 11, 2012
• Last Update Posted: October 11, 2012
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: January 25, 2008
• First Posted Date: February 7, 2008
• Results First Submitted Date: July 6, 2012
• Results First Posted Date: October 11, 2012
• Last Update Posted Date: October 11, 2012
• Study Start Date: April 2008
• Actual Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 10, 2012)

Progression-free Survival (PFS) [ Time Frame: Baseline, at every 8-week intervals for 18 months then every 12 weeks thereafter until disease progression (up to Week 115) ]

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").

• Original Primary Outcome Measures (submitted: January 25, 2008): Progression-free survival [ Time Frame: 18 months ]

Current Secondary Outcome Measures (submitted: September 10, 2012)

• Overall Survival (OS) [ Time Frame: 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) ]
  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).
• One Year Survival Probability [ Time Frame: 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) ]
  One year survival probability was defined as the probability of survival at one year after the first dose of study treatment.
• Two Year Survival Probability [ Time Frame: 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) ]
  Two year survival probability was defined as the probability of survival at two years after the first dose of study treatment.
• Percentage of Participants With Objective Response (OR) [ Time Frame: 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 ]
  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.
• Duration of Response (DR) [ Time Frame: 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 ]
  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.
• Change From Baseline in Functional Assessment of Cancer Treatment - Colorectal (FACT-C) Score [ Time Frame: 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) ]
  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.
• Change From Baseline in Functional Assessment of Cancer Treatment - Gynecologic Oncology Group Oxaliplatin-Specific Neurotoxicity (FACT&GOG-Ntx) Score [ Time Frame: Baseline (D1 of C1) then every 3 cycles thereafter and at the EOT or withdrawal visit (up to 115 weeks) ]
  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.

Original Secondary Outcome Measures (submitted: January 25, 2008)

• Overall survival and 1- and 2-year survival rates [ Time Frame: 36 months ]
• Objective response rate and duration of response [ Time Frame: 18 months ]
• Type, incidence, severity, timing, seriousness, and relatedness of adverse events [ Time Frame: 24 months ]
• Patient reported outcomes [ Time Frame: 18 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Randomized Study Of Sunitinib Plus FOLFOX Versus Bevacizumab Plus FOLFOX In Metastatic Colorectal Cancer
• Official Title: 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
• Brief Summary: 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: 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Colorectal Neoplasms

Intervention

• Drug: sunitinib
  Sunitinib: 37.5 mg/day, oral, administered on an outpatient basis for 4 weeks on, 2 weeks off (Schedule 4/2).
  Other Name: Sutent, SU011248
• Drug: mFOLFOX6
  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
• Drug: bevacizumab
  Bevacizumab: 5 mg/kg, IV infusion, every 2 weeks.
  Other Name: Avastin

Study Arms

• Experimental: A
  Treatment arm A - sunitinib plus mFOLFOX6
  Interventions:

  • Drug: sunitinib
  • Drug: mFOLFOX6
• Active Comparator: B
  Treatment arm B - bevacizumab plus mFOLFOX6
  Interventions:

  • Drug: bevacizumab
  • Drug: mFOLFOX6

• Publications *: Hecht JR, Mitchell EP, Yoshino T, Welslau M, Lin X, Chow Maneval E, Paolini J, Lechuga MJ, Kretzschmar A. 5-Fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus sunitinib or bevacizumab as first-line treatment for metastatic colorectal cancer: a randomized Phase IIb study. Cancer Manag Res. 2015 Jun 15;7:165-73. doi: 10.2147/CMAR.S61408. eCollection 2015.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: December 22, 2011): 191
• Original Estimated Enrollment (submitted: January 25, 2008): 290
• Actual Study Completion Date: July 2011
• Actual Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Denmark, Germany, Japan, United States

Administrative Information

• NCT Number: NCT00609622
• Other Study ID Numbers: A6181104
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

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

• PRS Account: Pfizer
• Verification Date: September 2012