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

Colorectal Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00609622
• Other study ID #: A6181104
• Status: Terminated
• Phase: Phase 2
• First received: January 25, 2008
• Last updated: September 10, 2012
• Start date: April 2008
• Est. completion date: July 2011

Study information

• Verified date: September 2012
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 191
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• 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).
• 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
• bevacizumab
Bevacizumab: 5 mg/kg, IV infusion, every 2 weeks.
• 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

Locations

Country	Name	City	State
Denmark	Pfizer Investigational Site	Aalborg
Denmark	Pfizer Investigational Site	Herlev
Denmark	Pfizer Investigational Site	Koebenhavn OE
Germany	Pfizer Investigational Site	Aschaffenburg
Germany	Pfizer Investigational Site	Bad Saarow
Germany	Pfizer Investigational Site	Berlin
Germany	Pfizer Investigational Site	Duesseldorf
Germany	Pfizer Investigational Site	Magdeburg
Germany	Pfizer Investigational Site	Mainz
Germany	Pfizer Investigational Site	Regensburg
Japan	Pfizer Investigational Site	Chuo-ku	Tokyo
Japan	Pfizer Investigational Site	Kashiwa	Chiba
Japan	Pfizer Investigational Site	Kitaadachi-gun, Ina-cho	Saitama
Japan	Pfizer Investigational Site	Sapporo	Hokkaido
Japan	Pfizer Investigational Site	Suntougun	Shizuoka
Japan	Pfizer Investigational Site	Utsunomiya	Tochigi
United States	Pfizer Investigational Site	Atlanta	Georgia
United States	Pfizer Investigational Site	Aurora	Colorado
United States	Pfizer Investigational Site	Bakersfield	California
United States	Pfizer Investigational Site	Baltimore	Maryland
United States	Pfizer Investigational Site	Baltimore	Maryland
United States	Pfizer Investigational Site	Beaumont	Texas
United States	Pfizer Investigational Site	Bentonville	Arkansas
United States	Pfizer Investigational Site	Chandler	Arizona
United States	Pfizer Investigational Site	Chanute	Kansas
United States	Pfizer Investigational Site	Columbia	Missouri
United States	Pfizer Investigational Site	Columbus	Mississippi
United States	Pfizer Investigational Site	Corinth	Mississippi
United States	Pfizer Investigational Site	Decatur	Georgia
United States	Pfizer Investigational Site	Dodge City	Kansas
United States	Pfizer Investigational Site	El Dorado	Kansas
United States	Pfizer Investigational Site	Fairhope	Alabama
United States	Pfizer Investigational Site	Fayetteville	Arkansas
United States	Pfizer Investigational Site	Fresno	California
United States	Pfizer Investigational Site	Fullerton	California
United States	Pfizer Investigational Site	Gainesville	Florida
United States	Pfizer Investigational Site	Henderson	Nevada
United States	Pfizer Investigational Site	Hot Springs	Arkansas
United States	Pfizer Investigational Site	Independence	Kansas
United States	Pfizer Investigational Site	Jacksonville	Florida
United States	Pfizer Investigational Site	Jacksonville	Florida
United States	Pfizer Investigational Site	Jacksonville	Florida
United States	Pfizer Investigational Site	Jacksonville Beach	Florida
United States	Pfizer Investigational Site	Jasonville	Florida
United States	Pfizer Investigational Site	Kingman	Kansas
United States	Pfizer Investigational Site	Lancaster	California
United States	Pfizer Investigational Site	Las Vegas	Nevada
United States	Pfizer Investigational Site	Las Vegas	Nevada
United States	Pfizer Investigational Site	Las Vegas	Nevada
United States	Pfizer Investigational Site	Liberal	Kansas
United States	Pfizer Investigational Site	Los Angeles	California
United States	Pfizer Investigational Site	Los Angeles	California
United States	Pfizer Investigational Site	Los Angeles	California
United States	Pfizer Investigational Site	Lubbock	Texas
United States	Pfizer Investigational Site	Macon	Georgia
United States	Pfizer Investigational Site	Marietta	Georgia
United States	Pfizer Investigational Site	Maryville	Illinois
United States	Pfizer Investigational Site	Meadowbrook	Pennsylvania
United States	Pfizer Investigational Site	Mesa	Arizona
United States	Pfizer Investigational Site	Mission Hills	California
United States	Pfizer Investigational Site	Mobile	Alabama
United States	Pfizer Investigational Site	Newton	Kansas
United States	Pfizer Investigational Site	Norman	Oklahoma
United States	Pfizer Investigational Site	Northrige	California
United States	Pfizer Investigational Site	Oklahoma City	Oklahoma
United States	Pfizer Investigational Site	Oklahoma City	Oklahoma
United States	Pfizer Investigational Site	Oklahoma City	Oklahoma
United States	Pfizer Investigational Site	Orange Park	Florida
United States	Pfizer Investigational Site	Oxnard	California
United States	Pfizer Investigational Site	Palatka	Florida
United States	Pfizer Investigational Site	Parsons	Kansas
United States	Pfizer Investigational Site	Pasadena	California
United States	Pfizer Investigational Site	Philadelphia	Pennsylvania
United States	Pfizer Investigational Site	Philadelphia	Pennsylvania
United States	Pfizer Investigational Site	Portland	Oregon
United States	Pfizer Investigational Site	Radnor	Pennsylvania
United States	Pfizer Investigational Site	Redondo Beach	California
United States	Pfizer Investigational Site	Salina	Kansas
United States	Pfizer Investigational Site	Sandy Springs	Georgia
United States	Pfizer Investigational Site	Santa Barbara	California
United States	Pfizer Investigational Site	Santa Maria	California
United States	Pfizer Investigational Site	Santa Monica	California
United States	Pfizer Investigational Site	Solvang	California
United States	Pfizer Investigational Site	St. Augustine	Florida
United States	Pfizer Investigational Site	Stuart	Florida
United States	Pfizer Investigational Site	Tulsa	Oklahoma
United States	Pfizer Investigational Site	Tulsa	Oklahoma
United States	Pfizer Investigational Site	Tulsa	Oklahoma
United States	Pfizer Investigational Site	Tupelo	Mississippi
United States	Pfizer Investigational Site	Valencia	California
United States	Pfizer Investigational Site	Washington	District of Columbia
United States	Pfizer Investigational Site	Wellington	Kansas
United States	Pfizer Investigational Site	Wenatchee	Washington
United States	Pfizer Investigational Site	Wichita	Kansas
United States	Pfizer Investigational Site	Wichita	Kansas
United States	Pfizer Investigational Site	Willow Grove	Pennsylvania
United States	Pfizer Investigational Site	Winfield	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Denmark,  Germany,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	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)	No
Secondary	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)	No

External Links

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