A Study of Capecitabine (Xeloda) and Bevacizumab as a First-line Therapy in Patients With Metastatic Colorectal Cancer
A 2x2 Factorial Randomized Phase III Study of Intermittent Oral Capecitabine in Combination With Intravenous Oxaliplatin (Q3W) ("XELOX") With/Without Intravenous Bevacizumab (Q3W) Versus Bolus and Continuous Infusion Fluorouracil/Intravenous Leucovorin With Intravenous Oxaliplatin (Q2W) ("FOLFOX-4") With/Without Intravenous Bevacizumab (Q2W) as First-line Treatment for Patients With Metastatic Colorectal Cancer
1 other identifier
interventional
2,035
32 countries
221
Brief Summary
This 4 arm study assessed the efficacy and safety of oral capecitabine (Xeloda) or intravenous (iv) fluorouracil/leucovorin, in combination with iv oxaliplatin (Eloxatin) with or without iv bevacizumab (Avastin), as a first-line treatment in patients with metastatic colorectal cancer. Patients were randomized to receive 1) XELOX (Xeloda 1000 mg/m\^2 orally \[po\] twice a day \[bid\] on Days 1-15 + oxaliplatin in 3 week cycles), 2) FOLFOX-4 (oxaliplatin + leucovorin + fluorouracil \[5-FU\] in 2 week cycles), 3) XELOX + bevacizumab (7.5 mg iv on Day 1 in 3 week cycles), or 4) FOLFOX-4 + bevacizumab (5 mg iv on Day 1 in 2 week cycles).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 colorectal-cancer
Started Jul 2003
Typical duration for phase_3 colorectal-cancer
221 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2003
CompletedFirst Submitted
Initial submission to the registry
September 15, 2003
CompletedFirst Posted
Study publicly available on registry
September 18, 2003
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2006
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2009
CompletedResults Posted
Study results publicly available
January 22, 2016
CompletedOctober 6, 2016
August 1, 2016
2.5 years
September 15, 2003
December 11, 2015
August 26, 2016
Conditions
Outcome Measures
Primary Outcomes (2)
Progression-free Survival (PFS) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) by General Approach (Participants With Curative Surgery Censored): Non-inferiority of XELOX Versus FOLFOX-4
PFS was defined as the time from randomization to progressive disease or death. Participants with neither disease progression nor death were censored at the last date of the last tumor assessment that confirmed that their disease had not progressed. Participants with no tumor assessments after baseline who were alive at the time of clinical cutoff were censored at the date of randomization. Participants who underwent surgical resection with curative intent without prior progression were censored at the date of surgery. PFS was based on tumor assessments made by the investigators according to the RECIST criteria. Non-inferiority analysis that followed the general approach took into account all tumor assessments obtained during the primary study treatment phase, the post-study treatment phase and those obtained during the follow-up phase. Non-inferiority of the XELOX-containing arms compared with the FOLFOX-4- containing arms was investigated.
Baseline until disease progression or death, approximately 2 years 6 months
PFS as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) by General Approach (Participants With Curative Surgery Censored) - Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
PFS was defined as the time from randomization to progressive disease or death. Participants with neither disease progression nor death were censored at the last date of the last tumor assessment that confirmed that their disease had not progressed. Participants with no tumor assessments after baseline who were alive at the time of clinical cutoff were censored at the date of randomization. Participants who underwent surgical resection with curative intent without prior progression were censored at the date of surgery. PFS was based on tumor assessments made by the investigators according to the RECIST criteria. Superiority analysis that followed the general approach took into account all tumor assessments obtained during the primary study treatment phase, the post-study treatment phase and those obtained during the follow-up phase. Superiority of the BV-containing arms was compared with the chemotherapy alone arms.
Baseline until disease progression or death, approximately 2 years 6 months
Secondary Outcomes (20)
PFS as Assessed by the Independent Review Committee (IRC) (General Approach, Participants With Curative Surgery Censored) - Non-inferiority of XELOX Versus FOLFOX-4
Baseline until disease progression or death, approximately 2 years 6 months
PFS as Assessed by the Independent Review Committee (IRC) (General Approach, Participants With Curative Surgery Censored) - Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
Baseline until disease progression or death, approximately 2 years 6 months
PFS (On-treatment Approach): Non-inferiority of XELOX Versus FOLFOX-4
Baseline until disease progression or death, approximately 2 years 6 months
PFS (On-treatment Approach): Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
Baseline until disease progression or death, approximately 2 years 6 months
PFS by General Approach, Participants With Curative Surgery Not Censored: Non-inferiority of XELOX Versus FOLFOX-4
Baseline until disease progression or death, approximately 2 years 6 months
- +15 more secondary outcomes
Study Arms (4)
XELOX (oxaliplatin+capecitabine)
EXPERIMENTALPatients in the 2-arm part of the study received oxaliplatin 130 mg/m\^2 intravenously (iv) on Day 1 of every 3 week cycle + capecitabine 1000 mg/m\^2 orally twice a day for the first 2 weeks of every 3 week cycle. Patients in the 4-arm part of the study received the same treatments plus placebo for bevacizumab 7.5 mg/kg iv on Day 1 of every 3 week cycle.
XELOX (oxaliplatin+capecitabine) + bevacizumab
EXPERIMENTALPatients in the 4-arm part of the study received oxaliplatin 130 mg/m\^2 intravenously (iv) on Day 1 of every 3 week cycle + capecitabine 1000 mg/m\^2 orally twice a day for the first 2 weeks of every 3 week cycle + bevacizumab 7.5 mg/kg iv on Day 1 of every 3 week cycle.
FOLFOX-4 (oxaliplatin+leucovorin+fluorouracil)
ACTIVE COMPARATORPatients in the 2-arm part of the study received oxaliplatin 85 mg/m\^2 intravenously (iv) + leucovorin 200 mg/m\^2 iv on Day 1 of every 2 week cycle + fluorouracil 400 mg/m\^2 bolus injection over 2 to 4 min followed by 600 mg/m\^2 continuous infusion over 22 h on Days 1 and 2 of every 2 week cycle. Patients in the 4-arm part of the study received the same treatments plus placebo for bevacizumab 5 mg/kg iv on Day 1 of every 2 week cycle.
FOLFOX-4 (oxaliplatin+leucovorin+fluorouracil) + bevacizumab
ACTIVE COMPARATORPatients in the 4-arm part of the study received oxaliplatin 85 mg/m\^2 intravenously (iv) + leucovorin 200 mg/m\^2 iv + bevacizumab 5 mg/kg iv on Day 1 of every 2 week cycle + fluorouracil 400 mg/m\^2 bolus injection over 2 to 4 min followed by 600 mg/m\^2 continuous infusion over 22 h on Days 1 and 2 of every 2 week cycle.
Interventions
Oxaliplatin was administered in a 2 h infusion before the first dose of capecitabine.
Capecitabine was taken within 30 min after the end of breakfast and dinner.
Bevacizumab was administered in a 30 to 90 min infusion.
Placebo control for bevacizumab (volume equivalent to 7.5 mg/kg bevacizumab) was administered in a 30 to 90 min infusion.
Oxaliplatin 85 mg/m\^2 was administered simultaneously with leucovorin in a 2 h infusion.
Leucovorin was administered simultaneously with oxaliplatin 85 mg/m\^2 in a 2 h infusion.
Bevacizumab was administered in a 30 to 90 min infusion.
Placebo control for bevacizumab (volume equivalent to 5 mg/kg bevacizumab) was administered in a 30 to 90 min infusion.
Eligibility Criteria
You may qualify if:
- Adult patients ≥ 18 years of age.
- Metastatic colorectal cancer.
- ≥ 1 target lesion.
You may not qualify if:
- Previous treatment with oxaliplatin or bevacizumab.
- Previous systemic chemotherapy or immunotherapy for advanced or metastatic disease.
- Progressive disease during or within 6 months of completion of previous adjuvant therapy.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (236)
Unknown Facility
Berkeley, California, 94704, United States
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Fountain Valley, California, 92708, United States
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Fullerton, California, 92835, United States
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Gilroy, California, 95020, United States
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Greenbrae, California, 94904, United States
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Los Angeles, California, 90057, United States
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Orange, California, 92868, United States
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Palo Alto, California, 94304, United States
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San Diego, California, 92123, United States
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Norwich, Connecticut, 06360, United States
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Waterbury, Connecticut, 06708, United States
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Boca Raton, Florida, 33486, United States
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Gainesville, Florida, 33610-0277, United States
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Jacksonville, Florida, 32207, United States
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New Port Richey, Florida, 34652, United States
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Tampa, Florida, 33607, United States
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Tampa, Florida, 33647, United States
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Atlanta, Georgia, 30341, United States
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Chicago, Illinois, 60640, United States
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Elk Grove Village, Illinois, 60007, United States
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Peoria, Illinois, 61615-7828, United States
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Lexington, Kentucky, 40536-0098, United States
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New Orleans, Louisiana, 70121, United States
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Scarborough, Maine, 04074, United States
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Boston, Massachusetts, 02135, United States
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Ann Arbor, Michigan, 48106, United States
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Saint Louis Park, Minnesota, 55416, United States
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Las Vegas, Nevada, 89106, United States
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East Orange, New Jersey, 07019, United States
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Hamilton, New Jersey, 08690, United States
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New Brunswick, New Jersey, 08901, United States
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Albuquerque, New Mexico, 87131-0001, United States
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Farmington, New Mexico, 87401, United States
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New York, New York, 10065, United States
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Rochester, New York, 14623, United States
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Syracuse, New York, 13210, United States
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Charlotte, North Carolina, 28203, United States
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Charlotte, North Carolina, 28233-3549, United States
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Bismarck, North Dakota, 58501, United States
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Fargo, North Dakota, 58122, United States
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Sayre, Pennsylvania, 18840, United States
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Upland, Pennsylvania, 19013, United States
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Providence, Rhode Island, 02906, United States
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Charleston, South Carolina, 29425, United States
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Columbia, South Carolina, 29209, United States
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Memphis, Tennessee, 38120, United States
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Houston, Texas, 77024, United States
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Burlington, Vermont, 05401, United States
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Richmond, Virginia, 23294, United States
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Adelaide, 5011, Australia
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Box Hill, 3128, Australia
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Brisbane, 4101, Australia
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Camperdown, 2050, Australia
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Fitzroy, 3065, Australia
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Footscray, 3011, Australia
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Kurralta Park, 5037, Australia
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Malvern, 3144, Australia
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Melbourne, 3002, Australia
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Melbourne, 3181, Australia
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Perth, 6000, Australia
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Port Macquarie, 2444, Australia
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St Leonards, 2065, Australia
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Sydney, 2031, Australia
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Sydney, 2139, Australia
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Vienna, 1090, Austria
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Wels, 4600, Austria
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Jaú, 17210-080, Brazil
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Rio de Janeiro, 20231-050, Brazil
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São Paulo, 05403-000, Brazil
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Calgary, Alberta, T2N 4N2, Canada
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Edmonton, Alberta, T6G 1Z2, Canada
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Kelowna, British Columbia, V1Y 5L3, Canada
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North Vancouver, British Columbia, V7L 2L7, Canada
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Surrey, British Columbia, V3V 1Z2, Canada
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Vancouver, British Columbia, V5Z 1H5, Canada
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Victoria, British Columbia, V8R 6V5, Canada
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Winnipeg, Manitoba, R2H 2A6, Canada
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Halifax, Nova Scotia, B3H 1V7, Canada
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Hamilton, Ontario, L8V 5C2, Canada
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London, Ontario, N6A 4L6, Canada
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Mississauga, Ontario, L5M 2N1, Canada
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Oshawa, Ontario, L1G 2B9, Canada
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Ottawa, Ontario, K1H 8L6, Canada
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St. Catharines, Ontario, L2R 7C6, Canada
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Toronto, Ontario, M4N 3M5, Canada
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Toronto, Ontario, M5G 1X5, Canada
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Toronto, Ontario, M5G 2M9, Canada
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Toronto, Ontario, M9N 1N8, Canada
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Lévis, Quebec, G6V 3Z1, Canada
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Montreal, Quebec, H1T 2M4, Canada
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Montreal, Quebec, H2L 4M1, Canada
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Montreal, Quebec, H4J 1C5, Canada
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Québec, Quebec, G1R 2J6, Canada
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Beijing, 100021, China
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Beijing, 100853, China
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Guangdong, 510515, China
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Guangzhou, 510060, China
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Jiangsu, 210009, China
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Jiangxi, 330000, China
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Shandong, 250117, China
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Shanghai, 200025, China
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Shanghai, 200092, China
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Tianjin, 300060, China
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Wuhan, 430030, China
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Brno, 656 53, Czechia
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Chomutov, 430 12, Czechia
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Hradec Králové, 500 36, Czechia
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Ostrava, 708 52, Czechia
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Copenhagen, 2100, Denmark
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Herlev, 2730, Denmark
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Odense, 5000, Denmark
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Helsinki, 00029, Finland
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Tampere, 33520, Finland
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Turku, 20520, Finland
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Besançon, 25030, France
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Bobigny, 93009, France
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Boulogne-Billancourt, 92104, France
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Brest, 29609, France
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Chambray-lès-Tours, 37171, France
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Colmar, 68024, France
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Dijon, 21079, France
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Grenoble, 38100, France
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Lyon, 69373, France
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Metz, 57072, France
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Nice, 06189, France
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Nice, 06202, France
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Nîmes, 30029, France
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Paris, 75475, France
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Paris, 75651, France
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Paris, 75679, France
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Pierre-Bénite, 69495, France
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Rouen, 76031, France
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Saint-Herblain, 44093, France
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Saint-Herblain, 44805, France
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Toulouse, 31052, France
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Bochum, 44892, Germany
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Halle, 06120, Germany
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Hanover, 30625, Germany
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Herne, 44625, Germany
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Leipzig, 04129, Germany
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Mainz, 55131, Germany
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Mannheim, 68167, Germany
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Regensburg, 93053, Germany
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Stralsund, 18435, Germany
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Trier, 54290, Germany
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Guatemala City, 01009, Guatemala
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Guatemala City, 01015, Guatemala
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Hong Kong, Hong Kong
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Budapest, 1082, Hungary
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Budapest, H-1122, Hungary
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Győr, 9002, Hungary
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Kecskemét, 6000, Hungary
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Cork, Ireland
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Dublin, 4, Ireland
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Dublin, 8, Ireland
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Galway, Ireland
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Haifa, 31096, Israel
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Jerusalem, 91120, Israel
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Petah Tikva, 49100, Israel
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Tel Aviv, 64239, Israel
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Ẕerifin, 70300, Israel
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Ancona, 60121, Italy
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Genova, 16132, Italy
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Modena, 41100, Italy
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Padua, 35100, Italy
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Parma, 43100, Italy
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Pavia, 27100, Italy
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Reggio Emilia, 42100, Italy
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Sassari, 07100, Italy
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Mexico City, 14000, Mexico
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Christchurch, New Zealand
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Bergen, 5021, Norway
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Oslo, 0407, Norway
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Tromsø, 9038, Norway
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Panama City, Panama
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Beja, 7801-849, Portugal
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Lisbon, 1649-035, Portugal
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San Juan, 00907, Puerto Rico
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Moscow, 105229, Russia
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Moscow, 115478, Russia
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Moscow, 117837, Russia
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Saint Petersburg, 197758, Russia
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Saint Petersburg, 198255, Russia
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Cape Town, 7506, South Africa
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Pretoria, 0001, South Africa
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Sandton, 2199, South Africa
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Seoul, 135-170, South Korea
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Barcelona, 08035, Spain
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Barcelona, 08036, Spain
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Córdoba, 14004, Spain
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Granada, 18014, Spain
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Leganés, 28911, Spain
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Madrid, 28007, Spain
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Madrid, 28034, Spain
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Madrid, 28040, Spain
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Madrid, 28041, Spain
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Madrid, 28046, Spain
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Málaga, 29010, Spain
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Santander, 39008, Spain
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Valencia, 46009, Spain
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Valencia, 46010, Spain
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Valencia, 46026, Spain
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Zaragoza, 50009, Spain
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Gävle, 80187, Sweden
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Karlstad, 65185, Sweden
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Stockholm, 17176, Sweden
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Uppsala, 751 85, Sweden
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Västerås, 72189, Sweden
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Bern, 3010, Switzerland
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Geneva, 1205, Switzerland
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Kueishan, 333, Taiwan
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Taipei, 100, Taiwan
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Taipei, 112, Taiwan
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Taipei, 114, Taiwan
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Bangkok, 10110, Thailand
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Bangkok, 10700, Thailand
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Khon Kaen, 40002, Thailand
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Istanbul, 34300, Turkey (Türkiye)
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Izmir, 35100, Turkey (Türkiye)
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Aberdeen, AB25 2ZN, United Kingdom
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Birmingham, B18 7QH, United Kingdom
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Cardiff, CF14 2TL, United Kingdom
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Derby, DE1 2QY, United Kingdom
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Glasgow, G12 0YN, United Kingdom
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Guildford, GU2 7XX, United Kingdom
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Hull, HU8 9HE, United Kingdom
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London, SW3 6JJ, United Kingdom
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Maidstone, ME16 9QQ, United Kingdom
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Newcastle upon Tyne, NE7 7DN, United Kingdom
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Northwood, HA6 2RN, United Kingdom
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Nottingham, NG5 1PB, United Kingdom
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Plymouth, PL6 8DH, United Kingdom
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Salisbury, SP2 8BJ, United Kingdom
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Southampton, SO9 4PE, United Kingdom
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Sutton, SM2 5PT, United Kingdom
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Taunton, TA1 5DA, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Roche Trial Information Hotline
- Organization
- F. Hoffmann-La Roche AG
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- FACTORIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 15, 2003
First Posted
September 18, 2003
Study Start
July 1, 2003
Primary Completion
January 1, 2006
Study Completion
April 1, 2009
Last Updated
October 6, 2016
Results First Posted
January 22, 2016
Record last verified: 2016-08