A Study Of Sunitinib In Combination With Capecitabine Compared With Capecitabine In Patients With Breast Cancer

A Randomized, Phase 3 Study Of Sunitinib In Combination With Capecitabine Compared With Capecitabine In Patients With Previously Treated Breast Cancer

The treatment received with sunitinib plus capecitabine could delay tumor growth longer than with treatment with capecitabine alone.

Study Overview

• Status: Completed
• Conditions: Breast Neoplasms
• Intervention / Treatment: Drug: Sunitinib + Capecitabine; Drug: Capecitabine

• Study Type: Interventional
• Enrollment (Actual): 442
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Linz, Austria, 4010
    • Pfizer Investigational Site
  • Salzburg, Austria, A-5020
    • Pfizer Investigational Site
  • Wels, Austria, A-4600
    • Pfizer Investigational Site
• Belgium
  • Leuven, Belgium, 3000
    • Pfizer Investigational Site
  • Liege, Belgium, 4000
    • Pfizer Investigational Site
  • Namur, Belgium, 5000
    • Pfizer Investigational Site
  • Turnhout, Belgium, 2300
    • Pfizer Investigational Site
  • Yvoir, Belgium, 5530
    • Pfizer Investigational Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Pfizer Investigational Site
    • Calgary, Alberta, Canada, T2S 3C3
      • Pfizer Investigational Site
  • Ontario
    • Oshawa, Ontario, Canada, L1G 2B9
      • Pfizer Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • Pfizer Investigational Site
    • Montreal, Quebec, Canada, H3G 1A4
      • Pfizer Investigational Site
    • Montreal, Quebec, Canada, H3T 1E2
      • Pfizer Investigational Site
    • Montreal, Quebec, Canada, H3T 1M5
      • Pfizer Investigational Site
    • Montreal, Quebec, Canada, H2W 1T8
      • Pfizer Investigational Site
• Czech Republic
  • Praha 4, Czech Republic, 140 59
    • Pfizer Investigational Site
  • Praha 5, Czech Republic, 150 06
    • Pfizer Investigational Site
  • Praha 5, Czech Republic, 15006
    • Pfizer Investigational Site
• Denmark
  • Aalborg, Denmark, 9100
    • Pfizer Investigational Site
  • Koebenhavn OE, Denmark, 2100
    • Pfizer Investigational Site
  • Odense, Denmark, 5000
    • Pfizer Investigational Site
• France
  • Angers cedex 01, France, 49033
    • Pfizer Investigational Site
  • BORDEAUX Cedex, France, 33076
    • Pfizer Investigational Site
  • CAEN Cedex 5, France, 14076
    • Pfizer Investigational Site
  • Lyon, France, Cedex 08
    • Pfizer Investigational Site
  • Nancy, France, 54100
    • Pfizer Investigational Site
  • Paris, France, 75231
    • Pfizer Investigational Site
  • Cedex 05
    • Montpellier, Cedex 05, France, 34059
      • Pfizer Investigational Site
• Germany
  • Erlangen, Germany, 91054
    • Pfizer Investigational Site
  • Frankenthal, Germany, 67227
    • Pfizer Investigational Site
  • Frankfurt am Main, Germany, 60590
    • Pfizer Investigational Site
  • Fuerstenwalde, Germany, 15517
    • Pfizer Investigational Site
  • Goettingen, Germany, 37099
    • Pfizer Investigational Site
  • Muenster, Germany, 48149
    • Pfizer Investigational Site
  • Nuernberg, Germany, 90419
    • Pfizer Investigational Site
  • Stendal, Germany, 39576
    • Pfizer Investigational Site
  • Ulm, Germany, 89075
    • Pfizer Investigational Site
  • Voelklingen, Germany, 66333
    • Pfizer Investigational Site
• Greece
  • Athens, Greece, 18547
    • Pfizer Investigational Site
  • Ioannina, Greece, 45 110
    • Pfizer Investigational Site
  • Patras, Greece, 26500
    • Pfizer Investigational Site
  • Thessaloniki, Greece, 564 03
    • Pfizer Investigational Site
  • Crete
    • Heraklion, Crete, Greece, 71 110
      • Pfizer Investigational Site
• Ireland
  • Dublin, Ireland, 4
    • Pfizer Investigational Site
  • Dublin, Ireland, 7
    • Pfizer Investigational Site
  • Dublin, Ireland, 8
    • Pfizer Investigational Site
• Italy
  • Bologna, Italy, 40138
    • Pfizer Investigational Site
  • Brescia, Italy, 25123
    • Pfizer Investigational Site
  • Messina, Italy, 98122
    • Pfizer Investigational Site
  • Milano, Italy, 20148
    • Pfizer Investigational Site
  • Palermo, Italy, 90127
    • Pfizer Investigational Site
  • Parma, Italy, 43100
    • Pfizer Investigational Site
  • Roma, Italy, 00144
    • Pfizer Investigational Site
  • Roma, Italy, 00133
    • Pfizer Investigational Site
  • Saronno (VA), Italy, 21047
    • Pfizer Investigational Site
  • Torino, Italy, 10126
    • Pfizer Investigational Site
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Pfizer Investigational Site
  • Sittard-geleen, Netherlands, 6162 BG
    • Pfizer Investigational Site
  • Zwolle, Netherlands, 8025 AB
    • Pfizer Investigational Site
• Norway
  • Levanger, Norway, 7600
    • Pfizer Investigational Site
  • Oslo, Norway, 0407
    • Pfizer Investigational Site
• Poland
  • Lodz, Poland, 93-509
    • Pfizer Investigational Site
  • Lublin, Poland, 20-090
    • Pfizer Investigational Site
  • Warszawa, Poland, 02-781
    • Pfizer Investigational Site
  • Warszawa, Poland, 00-909
    • Pfizer Investigational Site
• Romania
  • Cluj
    • Cluj-Napoca, Cluj, Romania, 400015
      • Pfizer Investigational Site
  • Sector 2
    • Bucuresti, Sector 2, Romania, 022328
      • Pfizer Investigational Site
• Russian Federation
  • Moscow, Russian Federation, 143423
    • Pfizer Investigational Site
  • St. Petersburg, Russian Federation, 197758
    • Pfizer Investigational Site
  • St. Petersburg, Russian Federation, 191104
    • Pfizer Investigational Site
  • Leningrad region
    • Kuzmolovo, Vsevolozhsk district, Leningrad region, Russian Federation, 188663
      • Pfizer Investigational Site
• Spain
  • Barcelona, Spain, 08036
    • Pfizer Investigational Site
  • Burgos, Spain, 09005
    • Pfizer Investigational Site
  • Cadiz, Spain, 11009
    • Pfizer Investigational Site
  • La Coruña, Spain, 15009
    • Pfizer Investigational Site
  • Madrid, Spain, 28034
    • Pfizer Investigational Site
  • Madrid, Spain, 28046
    • Pfizer Investigational Site
  • Sevilla, Spain, 41020
    • Pfizer Investigational Site
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Pfizer Investigational Site
  • Essex, United Kingdom, CM16 6TN
    • Pfizer Investigational Site
  • London, United Kingdom, W6 8RF
    • Pfizer Investigational Site
  • Swansea, United Kingdom, SA2 8QA
    • Pfizer Investigational Site
  • Truro, United Kingdom, TR1 3LJ
    • Pfizer Investigational Site
  • Worthing, United Kingdom, BN11 2DH
    • Pfizer Investigational Site
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • Pfizer Investigational Site
  • Essex
    • Chelmsford, Essex, United Kingdom, CM1 7WE
      • Pfizer Investigational Site
    • Harlow, Essex, United Kingdom, CM20 1QX
      • Pfizer Investigational Site
  • Staffordshire
    • Burton upon Trent, Staffordshire, United Kingdom, DE13 0RB
      • Pfizer Investigational Site
  • West Sussex
    • Worthing, West Sussex, United Kingdom, BN11 2DH
      • Pfizer Investigational Site
• United States
  • California
    • Downey, California, United States, 90241
      • Pfizer Investigational Site
    • Fresno, California, United States, 93720
      • Pfizer Investigational Site
    • Montebello, California, United States, 90640
      • Pfizer Investigational Site
    • Whittier, California, United States, 90606
      • Pfizer Investigational Site
  • Florida
    • Boca Raton, Florida, United States, 33428
      • Pfizer Investigational Site
    • Boynton Beach, Florida, United States, 33437
      • Pfizer Investigational Site
    • Coral Springs, Florida, United States, 33065
      • Pfizer Investigational Site
    • Hollywood, Florida, United States, 33021
      • Pfizer Investigational Site
    • Lake Worth, Florida, United States, 33467
      • Pfizer Investigational Site
    • Lakeland, Florida, United States, 33805
      • Pfizer Investigational Site
    • Miami, Florida, United States, 33125
      • Pfizer Investigational Site
    • Miami, Florida, United States, 33129
      • Pfizer Investigational Site
    • Miami, Florida, United States, 33133
      • Pfizer Investigational Site
    • Pembroke Pines, Florida, United States, 33028
      • Pfizer Investigational Site
  • Georgia
    • Duluth, Georgia, United States, 30096
      • Pfizer Investigational Site
    • Lawrenceville, Georgia, United States, 30045
      • Pfizer Investigational Site
    • Snellville, Georgia, United States, 30078
      • Pfizer Investigational Site
  • Indiana
    • Avon, Indiana, United States, 46123
      • Pfizer Investigational Site
    • Indianapolis, Indiana, United States, 46260
      • Pfizer Investigational Site
    • Mooresville, Indiana, United States, 46158
      • Pfizer Investigational Site
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Pfizer Investigational Site
    • Gretna, Louisiana, United States, 70056
      • Pfizer Investigational Site
    • Marrero, Louisiana, United States, 70072
      • Pfizer Investigational Site
    • Metairie, Louisiana, United States, 70006
      • Pfizer Investigational Site
    • Metairie, Louisiana, United States, 70002
      • Pfizer Investigational Site
    • New Orleans, Louisiana, United States, 70115
      • Pfizer Investigational Site
    • Shreveport, Louisiana, United States, 71103
      • Pfizer Investigational Site
  • Maryland
    • Kensington, Maryland, United States, 20895
      • Pfizer Investigational Site
    • Rockville, Maryland, United States, 20850
      • Pfizer Investigational Site
  • Mississippi
    • Corinth, Mississippi, United States, 38834
      • Pfizer Investigational Site
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Pfizer Investigational Site
  • Montana
    • Billings, Montana, United States, 59101
      • Pfizer Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Pfizer Investigational Site
    • Albuquerque, New Mexico, United States, 87106
      • Pfizer Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Pfizer Investigational Site
    • Charlotte, North Carolina, United States, 28204
      • Pfizer Investigational Site
    • Charlotte, North Carolina, United States, 28211
      • Pfizer Investigational Site
    • Charlotte, North Carolina, United States, 28262
      • Pfizer Investigational Site
    • Charlotte, North Carolina, United States, 28277
      • Pfizer Investigational Site
  • Oklahoma
    • Norman, Oklahoma, United States, 73071
      • Pfizer Investigational Site
    • Oklahoma City, Oklahoma, United States, 73120
      • Pfizer Investigational Site
    • Tulsa, Oklahoma, United States, 74133
      • Pfizer Investigational Site
    • Tulsa, Oklahoma, United States, 74136
      • Pfizer Investigational Site
    • Tulsa, Oklahoma, United States, 74104
      • Pfizer Investigational Site
  • Pennsylvania
    • Clairton, Pennsylvania, United States, 15025
      • Pfizer Investigational Site
    • Greensburg, Pennsylvania, United States, 15601
      • Pfizer Investigational Site
    • Pittsburgh, Pennsylvania, United States, 15213
      • Pfizer Investigational Site
    • Pittsburgh, Pennsylvania, United States, 15232
      • Pfizer Investigational Site
    • Pottstown, Pennsylvania, United States, 19464
      • Pfizer Investigational Site
    • Wexford, Pennsylvania, United States, 15090
      • Pfizer Investigational Site
  • Tennessee
    • Franklin, Tennessee, United States, 37067
      • Pfizer Investigational Site
    • Gallatin, Tennessee, United States, 37066
      • Pfizer Investigational Site
    • Hermitage, Tennessee, United States, 37076
      • Pfizer Investigational Site
    • Lebanon, Tennessee, United States, 37087
      • Pfizer Investigational Site
    • Memphis, Tennessee, United States, 38120
      • Pfizer Investigational Site
    • Murfreesboro, Tennessee, United States, 37130
      • Pfizer Investigational Site
    • Nashville, Tennessee, United States, 37203
      • Pfizer Investigational Site
    • Nashville, Tennessee, United States, 37205
      • Pfizer Investigational Site
    • Nashville, Tennessee, United States, 37207
      • Pfizer Investigational Site
    • Nashville, Tennessee, United States, 37211
      • Pfizer Investigational Site
    • Smyrna, Tennessee, United States, 37167
      • Pfizer Investigational Site
  • Texas
    • Austin, Texas, United States, 78705
      • Pfizer Investigational Site
    • Austin, Texas, United States, 78745
      • Pfizer Investigational Site
    • Austin, Texas, United States, 78757
      • Pfizer Investigational Site
    • Austin, Texas, United States, 78759
      • Pfizer Investigational Site
    • Beaumont, Texas, United States, 77701
      • Pfizer Investigational Site
    • Corpus Christi, Texas, United States, 78405
      • Pfizer Investigational Site
    • Corpus Christi, Texas, United States, 78410
      • Pfizer Investigational Site
    • Georgetown, Texas, United States, 78626
      • Pfizer Investigational Site
  • Utah
    • Bountiful, Utah, United States, 84010
      • Pfizer Investigational Site
    • Layton, Utah, United States, 84041
      • Pfizer Investigational Site
    • Murray, Utah, United States, 84157
      • Pfizer Investigational Site
    • Salt Lake City, Utah, United States, 84106
      • Pfizer Investigational Site
    • Salt Lake City, Utah, United States, 84102
      • Pfizer Investigational Site
    • West Provo, Utah, United States, 84604
      • Pfizer Investigational Site
    • West Valley City, Utah, United States, 84120
      • Pfizer Investigational Site
  • Virginia
    • Richmond, Virginia, United States, 23235
      • Pfizer Investigational Site
    • Richmond, Virginia, United States, 23298-0037
      • Pfizer Investigational Site
  • Washington
    • Kennewick, Washington, United States, 99336
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Locally advanced or metastatic disease that can be measured. Patients with bone-only disease are also allowed to enter the study.
• Previous treatment with an anthracycline and a taxane in any setting
• Progression on first or second line regimen or adjuvant regimen if disease free interval less than 12 months

Exclusion Criteria:

• History of inflammatory carcinoma if there is no other measurable disease
• More than 2 chemotherapy agents in the advanced disease setting
• Brain metastases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: B	Drug: Capecitabine; Capecitabine administered orally at a starting dose of 2500 mg/m^2 per day [1250 mg/m^2 bid (twice daily)] from days 1-14 every 3 weeks. Study treatment should be given until progression or withdrawal from the study for other reasons. At the time of progression, patients may be eligible to crossover to single agent sunitinib, administered orally at a starting dose of 37.5 mg daily.
Experimental: A	Drug: Sunitinib + Capecitabine; Sunitinib administered orally at a starting dose of 37.5 mg once a day on a continuous regimen. Capecitabine administered orally at a starting dose of 2000 mg/m^2 per day [1000 mg/m^2 bid (twice daily)] from days 1-14 every 3 weeks. Study treatment should be given until progression or withdrawal from the study for other reasons.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Defined as the time from the date of randomization to the date of the first documentation of objective tumor progression or death due to any cause, whichever occurs first. If tumor progression data include more than 1 date, the first date will be used. PFS (in months) will be calculated as (first event date minus randomization date plus 1) divided by 30.4.	Baseline until disease progression (up to 3 years from first dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response (OR)	Proportion of participants with confirmed complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST); CR: disappearance of all target lesions, PR: greater than or equal to (>=) 30 percent (%) decrease in the sum of the longest dimensions (SLD) of the target lesions taking as a reference the baseline SLD. Confirmed responses = persist on repeat imaging study at least 4 weeks after initial documentation of response. Designation of best response of stable disease (SD) required the criteria to be met at least 5 weeks after randomization.	Baseline until response or disease progression (up to 3 years from first dose)
Duration of Response (DR)	Time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of disease progression (PD) or to death due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. DR (in months) was calculated as [the date response ended (date of PD or death) minus first CR or PR date that was subsequently confirmed plus 1)] divided by 30.4.	Baseline until response or disease progression (up to 3 years from first dose)
Overall Survival (OS)	Time from the date of randomization to the date of death due to any cause. OS (in months) calculated as (date of death minus randomization date plus 1) divided by 30.4. For patients lacking survival data beyond the date of their last follow-up, the OS time was censored on the last date they were known to be alive. Patients lacking survival data beyond randomization had their OS times censored at randomization.	Baseline until death or up to 3 years from first dose
Percent Chance of Participant Survival	Probability of survival 2 years and 3 years after the first dose of study treatment.	Year 1, Year 2, Year 3
Change From Baseline in European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire (EORTC QLQ-C30)	EORTC QLQ-C30: global health/quality of life (QoL), functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much; global/QoL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms	Day 1 of each treatment cycle (up to 3 years or end of treatment)
Change From Baseline in European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire Breast Cancer Module (EORTC QLQ-BR23)	BR23: measured disease related symptoms of dry mouth, eye pain, hair loss, hot flushes, attractiveness, future health, sexual activity, arm/shoulder pain, breast pain, swollen breast, and skin problems on the breast. Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms.	Day 1 of each treatment cycle (up to 3 years or end of treatment)
Change From Baseline in EuroQol Group's EuroQol 5-Dimensional Self-Report Questionnaire (EQ-5D)	EQ-5D: health status in 5 dimensions (mobility, self-care, pain/discomfort, anxiety/depression, usual activities). Three-level scale (1=no problem, 2=some problem, and 3=extreme problem). A single score between 1 and 3 is generated for each domain. For each subject, the outcome rating on the 5 domains could be mapped to a single index through an algorithm. The index ranges between 0 and 1, with the higher score indicating a better health state perceived by the participant.	Day 1 of each treatment cycle (up to 3 years or end of treatment)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Crown JP, Dieras V, Staroslawska E, Yardley DA, Bachelot T, Davidson N, Wildiers H, Fasching PA, Capitain O, Ramos M, Greil R, Cognetti F, Fountzilas G, Blasinska-Morawiec M, Liedtke C, Kreienberg R, Miller WH Jr, Tassell V, Huang X, Paolini J, Kern KA, Romieu G. Phase III trial of sunitinib in combination with capecitabine versus capecitabine monotherapy for the treatment of patients with pretreated metastatic breast cancer. J Clin Oncol. 2013 Aug 10;31(23):2870-8. doi: 10.1200/JCO.2012.43.3391. Epub 2013 Jul 15.

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: February 13, 2007
• First Submitted That Met QC Criteria: February 13, 2007
• First Posted (Estimate): February 15, 2007

Study Record Updates

• Last Update Posted (Estimate): June 26, 2012
• Last Update Submitted That Met QC Criteria: June 15, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Capecitabine; Sunitinib
• Other Study ID Numbers: A6181099