Phase III Trial Comparing Capecitabine in Combination With Sorafenib or Placebo in the Treatment of Locally Advanced or Metastatic HER2-Negative Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Onyx Therapeutics, Inc.
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01234337
First received: October 4, 2010
Last updated: May 6, 2016
Last verified: May 2016
  Purpose
The objective of this phase-III trial is to compare the efficacy and safety of sorafenib in combination with capecitabine versus capecitabine in combination with placebo in the treatment of subjects with locally advanced or metastatic HER2-negative breast cancer who are resistant to or have failed prior taxane and an anthracycline or for whom further anthracycline therapy is not indicated. After signing consent there can be up to 28 days before starting the treatment during which time a number of tests will be carried out which will include tumor evaluations and medical history. The following tests and evaluations will have to be done within 7 days of the start of treatment,on Day 1 of every cycle and at the end of study: Electrocardiogram, blood tests, patient quality of life questionnaires and a complete physical exam and vital signs. Treatment will be given in 21 day cycles with sorafenib/placebo to be taken every day for 21 days and capecitabine to be taken for the first 14 days. Patients will come in weekly for the first 6 weeks and then on Day1 for every cycle after the first 2 cycles. During the weekly visits the subjects will be check for any side effects and blood draws will happen for the study on Day 1 of each cycle. Subjects will be followed for overall survival.

Condition Intervention Phase
Breast Cancer
Drug: Sorafenib(Nexavar, BAY43-9006)
Drug: Placebo
Drug: Capecitabine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III Randomized, Double Blind, Placebo-controlled Trial Comparing Capecitabine Plus Sorafenib Versus Capecitabine Plus Placebo in the Treatment of Locally Advanced or Metastatic HER2-Negative Breast Cancer

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Progression-free Survival (PFS) Assessed by the Independent Review Panel According to Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 [ Time Frame: From randomization of the first participant until approximately 3 years or until disease radiological progression ] [ Designated as safety issue: No ]
    PFS was defined as the time from date of randomization to disease progression, radiological or death due to any cause, whichever occurs first. Per RECIST version 1.1, progressive disease was determined when there was at least 20% increase in the sum of diameters of the target lesions, taking as a reference the smallest sum on study (this included the baseline sum if that was the smallest sum on trial). In addition to a relative increase of 20%, the sum had demonstrated an absolute increase of at least 5 mm. Appearance of new lesions and unequivocal progression of existing non-target lesions was also interpreted as progressive disease. Participants without progression or death at the time of analysis were censored at their last date of evaluable tumor evaluation. Median and other 95% confidence intervals (CIs) computed using Kaplan-Meier estimates.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: From randomization of the first participant until approximately 3 years later ] [ Designated as safety issue: No ]
    OS was defined as the time from date of randomization to death due to any cause. Participants still alive at the time of analysis were censored at their last known alive date. Median and other 95% CIs computed using Kaplan-Meier estimates.

  • Time to Progression (TTP) by Central Review [ Time Frame: From randomization of the first participant until approximately 3 years later or until disease radiological progression ] [ Designated as safety issue: No ]
    TTP was defined as the time from date of randomization to disease radiological progression by central review. Per RECIST version 1.1, progressive disease was determined when there was at least 20% increase in the sum of diameters of the target lesions, taking as a reference the smallest sum on study (this included the baseline sum if that was the smallest sum on trial). In addition to a relative increase of 20%, the sum had demonstrated an absolute increase of at least 5 mm. Appearance of new lesions and unequivocal progression of existing non-target lesions was also interpreted as progressive disease. Participants without progression or death at the time of analysis were censored at their last date of evaluable tumor evaluation. Median and other 95% confidence intervals (CIs) computed using Kaplan-Meier estimates.

  • Objective Response Rate (ORR) by Central Review [ Time Frame: From randomization of the first participant until approximately 3 years later or until disease radiological progression ] [ Designated as safety issue: No ]
    ORR was defined as the best tumor response (Complete Response [CR] or Partial Response [PR]) observed during treatment or within 30 days after termination of study treatment, assessed according to the RECIST version 1.1. CR=all target lesions disappeared, and any pathological lymph node, whether target or non-target, had a reduction in short axis to <10 mm. If any residual lesion was present, cyto-histology was made available to unequivocally document benignity. PR=at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR=CR+PR. CR and PR were confirmed by another scan at least 4 weeks later.

  • Disease Control Rate (DCR) by Central Review [ Time Frame: From randomization of the first participant until approximately 3 years later or until disease radiological progression ] [ Designated as safety issue: No ]
    DCR was defined as the proportion of participants whose best response was CR, PR, stable disease (SD) or Non-CR/Non-PD. Per RECIST version 1.1, CR=all target lesions disappeared, any pathological lymph node, target/non-target, a reduction in short axis to <10 mm. PR=at least 30% decrease in the sum of diameters of target lesions taking as reference baseline sum diameters. PD=at least 20% increase in the sum of diameters of the target lesions, taking as a reference smallest sum on study. Appearance of new lesions and unequivocal progression of existing non-target lesions. SD=neither sufficient shrinkage qualified for PR nor sufficient increase qualified for PD, taking smallest sum of diameters as a reference. Non-CR/Non-PD=persistence of 1/more non-target lesion(s) and/or maintenance of tumor marker level above normal limits. DCR=CR+PR+SD or Non-CR/Non-PD. CR and PR confirmed by another scan at least 4 weeks later. SD and Non-CR/Non-PD documented at least 6 weeks after randomization.

  • Duration of Response (DOR) by Central Reader [ Time Frame: From randomization of the first participant until approximately 3 years later or until disease radiological progression ] [ Designated as safety issue: No ]
    DOR was defined as the time from date of first response (CR or PR) to the date when PD is first documented, or to the date of death, whichever occurred first according to RECIST version 1.1. CR=all target lesions disappeared, and any pathological lymph node, whether target or non-target, had a reduction in short axis to <10 mm. If any residual lesion was present, cyto-histology was made available to unequivocally document benignity. PR=at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants still having CR or PR and have not died at the time of analysis were censored at their last date of tumor evaluation. DOR defined for confirmed responders only (that is, CR or PR). 'NA' indicates that value could not be estimated due to censored data. Median and 95% CIs were computed using Kaplan-Meier estimates.


Other Outcome Measures:
  • Patient Reported Outcomes: Functional Assessment of Cancer Therapy-Breast Symptom Index (8 Item) (FBSI-8) [ Time Frame: Day 1 of Cycles 1, 3, 5, 7, 9, 11, 13, 16, 19, 22, 25, 28, 31, 34, 37, and end of treatment (EOT, 21 days after last dose of study drug) ] [ Designated as safety issue: No ]
    The FBSI-8 was an 8-item questionnaire. Participants responded to each item using a 5-point Likert-type scale ranging from 0 (not at all) to 4 (very much). A total scale score was calculated (range from 0 to 32), with higher scores indicating low symptomatology and reflecting a better Health-Related Quality of Life (HRQoL). The results on the analysis of covariance (ANCOVA) of time-adjusted area under curve (AUC) for the FBSI-8 score were reported. The time-adjusted AUC was calculated by dividing the AUC by duration (in days) over the period of interest, and reported as 'scores on a scale'.

  • Patient Reported Outcomes: Euroqol-5 Dimensions (EQ-5D) - Index Score [ Time Frame: Day 1 of Cycles 1, 3, 5, 7, 9, 11, 13, 16, 19, 22, 25, 28, and EOT (21 days after last dose of study drug) ] [ Designated as safety issue: No ]
    The EQ-5D was a generic Quality of life (QoL) based instrument validated in cancer populations. EQ-5D questionnaire contained a 5-item descriptive system of health states (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and visual analogue scale (VAS). A single HRQoL score ranging from -0.59 to 1 was generated from standard scoring algorithm developed by the EuroQoL was the EQ-5D index score, higher scores represent better health status. A change of at least 0.10 to 0.12 points was considered clinically meaningful. The results on the ANCOVA of time-adjusted AUC for the EQ-5D - Index Score were reported. The time-adjusted AUC was calculated by dividing the AUC by duration (in days) over the period of interest, and reported as 'scores on a scale'.

  • Patient Reported Outcomes: Euroqol-5 Dimensions (EQ-5D) - Visual Analogue Scale (VAS) Score [ Time Frame: Day 1 of Cycles 1, 3, 5, 7, 9, 11, 13, 16, 19, 22, 25, 28, and EOT (21 days after last dose of study drug) ] [ Designated as safety issue: No ]
    The EQ-5D was a generic QoL preference based instrument and has been validated in the cancer populations. VAS was generated from 0 (worst imaginable health state) to 100 (best imaginable health state). This VAS score was referred to as the EQ-5D self-reported health status score. The results on ANCOVA of time-adjusted AUC were reported. The time-adjusted AUC was calculated by dividing the AUC by duration (in days) over the period of interest, and reported as 'scores on a scale'.

  • Maximum Observed Drug Concentration (Cmax) of Capecitabine and 5-fluorouracil [ Time Frame: Pre-dose and 0.5, 1, 2, and 4 hours after capecitabine dosing at Cycle 2, Day 14 ] [ Designated as safety issue: No ]
    Maximum observed drug concentration, directly taken from analytical data. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. In the listed categories below, 'N' signifies the number of evaluable participants for the drug administered.

  • Area Under Curve From Time Zero to Last Quantifiable Concentration (AUC[0-tlast]) of Capecitabine and 5-fluorouracil [ Time Frame: Pre-dose and 0.5, 1, 2, and 4 hours after capecitabine dosing at Cycle 2, Day 14 ] [ Designated as safety issue: No ]
    AUC(0-tlast) is defined as AUC from time 0 to the last data point, calculated up by linear trapezoidal rule, down by logarithmic trapezoidal rule. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. In the listed categories below, 'N' signifies the number of evaluable participants for the drug administered.

  • Number of Participants With Treatment-emergent Grade 3 and 4 Laboratory Abnormalities [ Time Frame: From the start of study treatment up to 30 days after the last dose ] [ Designated as safety issue: Yes ]
    Hematological (anemia, hemoglobin, international normalized ratio [INR], lymphocyte, neutrophil, platelet, white blood cell [WBC]), biochemical (ALT [alanine aminotransferase], AST [aspartate aminotransferase], GGT [gamma-glutamyl-transferase], lipase, hypoalbuminemia, hypocalcemia, hyperglycemia, hyperuricemia) evaluations were done. Common terminology criteria for adverse events (CTCAE) version 4-Grade 3: Severe or medically significant; hospitalization or prolongation of hospitalization and CTCAE version 4-Grade 4: life-threatening consequences; urgent intervention were indicated.


Enrollment: 537
Study Start Date: February 2011
Estimated Study Completion Date: December 2016
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sorafenib(Nexavar, BAY43-9006) + Capecitabine
Capecitabine was administered orally at a dose of 1,000 milligram per square meter (mg/m^2) twice daily (12 hours apart) on Days 1 through 14 of each 21-day cycle. Sorafenib was administered orally at a dose of 600 mg (200 mg in the morning, 400 mg in the evening) daily, continuously (that is, Days 1 to 21, inclusive). A treatment cycle consisted of 21 days. If tolerability criteria were met for a subject, capecitabine dose was escalated to 1,250 mg/m^2 twice daily and sorafenib dose to a total daily dose of 800 mg for that subject.
Drug: Sorafenib(Nexavar, BAY43-9006)
Capecitabine was administered orally at a dose of 1,000 milligram per square meter (mg/m^2) twice daily (12 hours apart) on Days 1 through 14 of each 21-day cycle. Sorafenib was administered orally at a dose of 600 mg (200 mg in the morning, 400 mg in the evening) daily, continuously (that is, Days 1 to 21, inclusive). A treatment cycle consisted of 21 days. If tolerability criteria were met for a subject, capecitabine dose was escalated to 1,250 mg/m^2 twice daily and sorafenib dose to a total daily dose of 800 mg for that subject.
Drug: Capecitabine
Capecitabine was administered orally at a dose of 1,000 milligram per square meter (mg/m^2) twice daily (12 hours apart) on Days 1 through 14 of each 21-day cycle.days. If tolerability criteria were met for a subject, capecitabine dose was escalated to 1,250 mg/m^2 twice daily,
Placebo Comparator: Placebo + Capecitabine
Capecitabine was administered orally at a dose of 1,000 mg/m^2 twice daily (12 hours apart) on Days 1 through 14 of each 21-day cycle. Placebo matching to sorafenib was administered orally, 3 tablets (1 tablet in the morning, 2 tablets in the evening) daily, continuously (that is, Days 1 to 21, inclusive). A treatment cycle consisted of 21 days. If tolerability criteria were met for a subject, capecitabine dose was escalated to 1,250 mg/m^2 twice daily and placebo dose to a total daily dose of 4 tablets (2 tablets twice daily) for that subject.
Drug: Placebo
Capecitabine was administered orally at a dose of 1,000 mg/m^2 twice daily (12 hours apart) on Days 1 through 14 of each 21-day cycle. Placebo matching to sorafenib was administered orally, 3 tablets (1 tablet in the morning, 2 tablets in the evening) daily, continuously (that is, Days 1 to 21, inclusive). A treatment cycle consisted of 21 days. If tolerability criteria were met for a subject, capecitabine dose was escalated to 1,250 mg/m^2 twice daily and placebo dose to a total daily dose of 4 tablets (2 tablets twice daily) for that subject.
Drug: Capecitabine
Capecitabine was administered orally at a dose of 1,000 milligram per square meter (mg/m^2) twice daily (12 hours apart) on Days 1 through 14 of each 21-day cycle.days. If tolerability criteria were met for a subject, capecitabine dose was escalated to 1,250 mg/m^2 twice daily,

Detailed Description:

Research summary (NRES, UK):

Breast cancer is the most commonly diagnosed cancer in women and the leading cause of cancer-related death among women worldwide.

However, despite advances in treatment of the early-stage disease, about 25-40% of patients will develop recurrence or spread to other parts of the body that is largely incurable. The average survival of patients with breast cancer that has spread to other parts of the body (metastasis) is 2 to 3 years after diagnosis, and although a number of treatment options are available, including various chemotherapy agents, no single standard of care exists.

The study drug (Sorafenib) works by inhibiting certain pathways in the body that contribute to tumour growth and the formation of new blood vessels (angiogenesis). Angiogenesis plays an important role in the development, transformation and spread of breast cancer. Capecitabine is an approved chemotherapy drug for patients whose breast cancer has spread to other parts of the body (metastatic) and is not responsive to other classes of chemotherapy drugs.

Data from a Phase IIb clinical study suggests that there is a role for the combination of Sorafenib and Capecitabine to treat locally advanced or metastatic breast cancer.

Patients in this confirmatory Phase III study will be randomly assigned to receive either:

  • Capecitabine + Sorafenib
  • Capecitabine + placebo ("dummy medication" with no active drug)

Participants will continue to receive treatments until there is radiographic or clinical progression of disease, side effects which require them to withdraw, pregnancy, protocol non-compliance or withdrawal of consent. Therefore length of participation will vary for individuals. This study is expected to close 31 March 2013.

This is a multicentre study which will take place across Europe, North and South America, Asia, Australia and South Africa. It is anticipated that approximately 519 participants will be recruited worldwide.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age is >=18 years
  • Subject has histologically or cytologically confirmed HER2-negative adenocarcinoma of the breast. HER2 status should be determined by an accredited laboratory
  • Subject has locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent. Must have measurable or non-measurable disease (according to RECIST [Response Evaluation Criteria for Solid Tumors] 1.1)
  • All computer tomography (CT; with contrast) and magnetic resonance imaging (MRI) used to document disease must have been done <= 4 weeks before randomization. Bone scans (if clinically indicated) must have been done <= 12 weeks prior to randomization
  • Subject must have received up to two prior chemotherapy regimens (adjuvant/neo-adjuvant treatments are considered one regimen), and no more than one prior regimen for advanced and/or metastatic disease. Chemotherapy regimens include both targeted and biologic therapy
  • Prior regimens must have included an anthracycline (eg, doxorubicin, epirubicin) and a taxane (eg, paclitaxel, docetaxel), either in combination or in separate regimens, in either the neo-adjuvant/adjuvant or the metastatic setting or both, as either monotherapy or as part of a combination with another agent. Sequential regimens will count as a single regimen; multiple neo-adjuvant / adjuvant regimens will count as a single regimen
  • Subjects are either resistant to or have failed prior taxane and anthracycline OR Resistant to or have failed prior taxane AND for whom further anthracycline therapy is not indicated (for example, intolerance or cumulative doses of doxorubicin or doxorubicin equivalents [for example, epirubicin)
  • Subjects who relapse beyond 12 months after the last taxane or anthracycline dose given in the adjuvant, neo-adjuvant, or metastatic setting are eligible. Further therapy with the agent(s) for a subsequent regimen must have been considered and ruled out, for example due to prior toxicity or intolerance, or based on the local standard of practice
  • Prior experimental chemotherapy treatment is allowed, provided it is given in combination with at least one drug approved for the treatment of breast cancer (excluding drugs that target VEGF [Vascular Endothelial Growth Factor] or VEGFR [Vascular Endothelial Growth Factor Receptor], eg, bevacizumab, brivanib, sunitinib, vatalinib).
  • Prior hormonal therapy for locally advanced or metastatic breast cancer is allowed. Subjects who are refractory to hormonal therapy are allowed.
  • Prior neo-adjuvant or adjuvant chemotherapy is allowed.
  • Subject must have discontinued prior chemotherapy (including both targeted and biologic therapies), prior therapeutic radiation therapy, or prior hormonal therapy for locally advanced or metastatic disease >= 4 weeks (28 days) before randomization. Start of study treatment is allowed within less than 28 days of the prior therapy provided that 5 half-lives of the prior treatment drug(s) have elapsed
  • ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1
  • Adequate bone marrow, liver and renal function within 7 days prior to randomization
  • All acute toxic effects of any prior treatment have resolved to NCI-CTCAE (National Cancer Institute-Common Terminology Criteria for Adverse Events) v4.0 Grade 1 or less
  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to randomization
  • Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF (Informed Consent Form) until at least 30 days after the last dose of study drug.
  • Subject must be able to swallow and retain oral medication

Exclusion Criteria:

  • HER2 positive breast cancer
  • Unknown hormone receptor status (estrogen and progesterone receptor).
  • Subjects with bilateral breast cancer or a history of two distinct breast cancers.
  • Subjects with inflammatory breast carcinoma.
  • Subjects who have received no prior taxane and anthracycline for the treatment of breast cancer (either in adjuvant, neo-adjuvant or metastatic setting).
  • Prior use of sorafenib or capecitabine
  • Subjects considered by the treating investigator to be appropriate candidates for hormonal therapy as current treatment for locally advanced/metastatic breast cancer
  • Subjects with locally advanced disease who are considered by the treating investigator to be appropriate candidates for radiation therapy as current treatment for locally advanced breast cancer
  • Subjects with active brain metastases or leptomeningeal disease.
  • Subjects with seizure disorder requiring medication.
  • Radiation to any lesions <= 4 weeks prior to randomization. Palliative radiation to bone metastasis for pain control is permitted with provisions
  • Major surgery, open biopsy, or significant traumatic injury <= 4 weeks
  • Evidence or history of bleeding diathesis or coagulopathy. Uncontrolled hypertension, active or clinically significant cardiac disease. Subject with thrombotic, embolic, venus or arterial events
  • Subjects with any hemorrhage/bleeding event of NCI-CTCAE v4.0 Grade 3 or higher within 4 weeks before randomization
  • Subjects with an infection of NCI-CTCAE v4.0 > Grade 2
  • Subjects with a history of human immunodeficiency virus infection or current chronic or active hepatitis B or C infection.
  • Subjects who have used strong CYP3A4 inducers (eg, phenytoin, carbamazepine, phenobarbital, St. John's Wort [Hypericum perforatum], dexamethasone at a dose of greater than 16 mg daily, or rifampin [rifampicin], and/or rifabutin) within 28 days before randomization.
  • Subjects with any previously untreated or concurrent cancer that is distinct in primary site or histology from breast cancer
  • Subjects with a history DHPD (Dihydropyrimidine dehydrogenase) reaction to fluropyrimidine or history of known or suspected allergy or hypersensitivity to any of the study drugs
  • Presence of a non-healing wound, non-healing ulcer, or bone fracture
  • Women pregnant or breast feeding
  • Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01234337

  Hide Study Locations
Locations
United States, California
Greenbrae, California, United States, 94904-2007
La Jolla, California, United States, 92093
Sylmar, California, United States, 91342
United States, Florida
Davie, Florida, United States, 33328
Jacksonville, Florida, United States, 32209
Lake City, Florida, United States, 32024
West Palm Beach, Florida, United States, 33407
United States, Georgia
Atlanta, Georgia, United States, 30322
United States, Illinois
Chicago, Illinois, United States, 60611
Joliet, Illinois, United States, 60435
United States, Indiana
Evansville, Indiana, United States, 47713
United States, Kentucky
Hazard, Kentucky, United States, 41701
Louisville, Kentucky, United States, 40207
United States, Louisiana
New Orleans, Louisiana, United States, 70121
United States, Massachusetts
Boston, Massachusetts, United States, 02130
Boston, Massachusetts, United States, 02115-6084
Boston, Massachusetts, United States, 02114
Burlington, Massachusetts, United States, 01805
United States, Mississippi
Jackson, Mississippi, United States, 39202
United States, Missouri
Springfield, Missouri, United States, 65804
United States, New Mexico
Albuquerque, New Mexico, United States, 87131
United States, New York
Lake Success, New York, United States, 11042
United States, North Carolina
Durham, North Carolina, United States, 27710
Winston-Salem, North Carolina, United States, 24103
United States, Pennsylvania
Danville, Pennsylvania, United States, 17822-2001
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Bristol, Tennessee, United States, 37620
Memphis, Tennessee, United States, 38120
United States, Texas
El Paso, Texas, United States, 79905
United States, Vermont
Burlington, Vermont, United States, 05405
United States, Virginia
Abingdon, Virginia, United States, 24211
United States, Washington
Seattle, Washington, United States, 98109-1023
Tacoma, Washington, United States, 98431-5000
United States, Wisconsin
Madison, Wisconsin, United States, 53792
Racine, Wisconsin, United States, 53405
Weston, Wisconsin, United States, 54476
Argentina
La Plata, Buenos Aires, Argentina, B1902CMK
Mar del Plata, Buenos Aires, Argentina, B7600CTO
Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1280AEB
Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1425AWC
Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina
Córdoba, Argentina, X5004BAL
Santa Fé, Argentina, S3000FFV
Australia, Australian Capital Territory
Garran, Australian Capital Territory, Australia, 2605
Australia, New South Wales
Liverpool, New South Wales, Australia, 2170
Waratah, New South Wales, Australia, 2298
Australia, South Australia
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Bendigo, Victoria, Australia, 3550
Fitzroy, Victoria, Australia, 3065
Frankston, Victoria, Australia
Australia, Western Australia
Perth, Western Australia, Australia, 6000
Austria
Linz, Oberösterreich, Austria, 4010
Wien, Austria, 1100
Belgium
Liege, Liège, Belgium, 4000
Brugge, Belgium, 8000
Bruxelles - Brussel, Belgium, 1000
Edegem, Belgium, 2650
Hasselt, Belgium, 3500
La Louviere, Belgium, 7100
Brazil
Fortaleza, Ceará, Brazil, 60160-230
Fortaleza, Ceará, Brazil, 60430-230
Cachoeiro de Itapemirim, Espírito Santo, Brazil, 29308-020
Goiania, Goiás, Brazil, 74140-050
Goiânia, Goiás, Brazil, 74605-180
Belo Horizonte, Minas Gerais, Brazil, 30110-090
Ijuí, Rio Grande do Sul, Brazil, 98700-000
Porto Alegre, Rio Grande do Sul, Brazil, 90110-270
Porto Alegre, Rio Grande do Sul, Brazil, 90430-090
Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
Porto Alegre, Rio Grande do Sul, Brazil
Florianópolis, Santa Catarina, Brazil, 88034-000
Itajaí, Santa Catarina, Brazil, 88301-220
Jaú, Sao Paulo, Brazil, 17210-120
Piracicaba, Sao Paulo, Brazil, 13416-225
São Paulo, Sao Paulo, Brazil, 03102 002
Sao Paulo, Brazil, 01317-000
Sao Paulo, Brazil, 01509-900
Canada, Ontario
Weston, Ontario, Canada, M9N 1N8
Canada, Quebec
Montreal, Quebec, Canada, H2L 4M1
Montreal, Quebec, Canada, H3G 1A4
Chile
Santiago, Chile, 838-0455
Santiago, Chile
China, Liaoning
Shenyang, Liaoning, China, 110001
China, Shaanxi
Xi'an, Shaanxi, China, 710032
China
Beijing, China, 100021
Beijing, China, 100071
Nanning, China, 530021
Shanghai, China, 200030
Tianjin, China, 300060
Czech Republic
Ceske Budejovice, Czech Republic, 370 01
Nova Ves Pod Plesi, Czech Republic, 262 04
Nymburk, Czech Republic, 288 02
Olomouc, Czech Republic, 775 20
Praha, Czech Republic, 18081
Praha 10, Czech Republic, 10034
Praha 2, Czech Republic, 128 08
Praha 5, Czech Republic, 150 06
Praha 5, Czech Republic, 150 30
France
ANGERS cedex 9, France, 49933
Clermont Ferrand Cedex 1, France, 63011
Lille, France, 59020
Nantes, France, 44805
Saint Cloud, France, 92210
Toulouse, France, 31052
Germany
Erlangen, Bayern, Germany, 91054
Frankfurt, Hessen, Germany, 60389
Langen, Hessen, Germany, 63225
Offenbach, Hessen, Germany, 63069
Köln, Nordrhein-Westfalen, Germany, 50931
Köln, Nordrhein-Westfalen, Germany, 51067
Mainz, Rheinland-Pfalz, Germany, 55131
Magdeburg, Sachsen-Anhalt, Germany, 38108
Stendal, Sachsen-Anhalt, Germany, 39576
Chemnitz, Sachsen, Germany, 09116
Leipzig, Sachsen, Germany, 04103
Berlin, Germany, 13589
Hamburg, Germany, 22081
Greece
Athens, Attica, Greece, 11528
Athens, Greece, 11527
Heraklion, Greece, 711 10
Ioannina, Greece, 45500
Larissa, Greece, 41100
Patra, Greece, 26500
Pylaia / Thessaloniki, Greece, 57010
Thessaloniki, Greece, 540 07
Hungary
Budapest, Hungary, 1032
Nyíregyháza, Hungary, H-4400
Pecs, Hungary, 7624
Szekesfehervar, Hungary, 8000
Szentes, Hungary, H-6600
Szolnok, Hungary, H-5004
Ireland
Dooradoyle, Limerick, Ireland
Cork, Ireland
Dublin, Ireland, 7
Dublin, Ireland, 9
Dublin, Ireland, DUBLIN 4
Dublin, Ireland, DUBLIN 8
Galway, Ireland
Israel
Beer Sheva, Israel, 8410101
Haifa, Israel, 3109601
Haifa, Israel, 35152
Jerusalem, Israel, 9112001
Jerusalem, Israel, 9372212
Petah Tikva, Israel, 4941492
Ramat Gan, Israel, 5262000
Zrifin, Israel, 6093000
Italy
Meldola, Forlì, Italy, 47014
Rozzano, Milano, Italy, 20089
Monza, Monza-Brianza, Italy, 20900
Ancona, Italy, 60126
Bologna, Italy, 40138
Cremona, Italy, 26100
Genova, Italy, 16132
Lecce, Italy, 73100
Modena, Italy, 41124
Palermo, Italy, 90127
Pavia, Italy, 27100
Pisa, Italy, 56126
Ravenna, Italy, 48100
Roma, Italy, 00161
Japan
Nagoya, Aichi, Japan, 464-8681
Matsuyama, Ehime, Japan, 791-0280
Suita, Osaka, Japan, 565-0871
Hidaka, Saitama, Japan, 350-1298
Kita-Adachigun, Saitama, Japan, 362-0806
Bunkyo, Tokyo, Japan, 113-8677
Koto-ku, Tokyo, Japan, 135-8550
Chiba, Japan, 260-8717
Fukuoka, Japan, 811-1395
Kagoshima, Japan, 892-0833
Osaka, Japan, 540-0006
Poland
Gdansk, Poland, 80-952
Gdynia, Poland, 81-519
Krakow, Poland, 31-115
Lodz, Poland, 93-509
Poznan, Poland, 61-485
Szczecin, Poland, 70-115
Warszawa, Poland, 04-125
Puerto Rico
San Juan, Puerto Rico, 00918
Russian Federation
Chelyabinsk, Russian Federation, 454087
Kazan, Russian Federation, 420029
Moscow, Russian Federation, 115478
St. Petersburg, Russian Federation, 188663
Ufa, Russian Federation, 450054
South Africa
Port Elizabeth, Eastern Cape, South Africa, 6045
Johannesburg, Gauteng, South Africa, 2196
Pretoria, Gauteng, South Africa, 0081
Pretoria, Gauteng, South Africa, 0084
Pretoria, Gauteng, South Africa, 0181
Sandton, Gauteng, South Africa, 2199
Cape Town, Western Cape, South Africa
Spain
Santiago de Compostela, A Coruña, Spain, 15706
Sabadell, Barcelona, Spain, 08208
Terrassa, Barcelona, Spain, 08221
Castellón de la Plana, Castellón, Spain, 12002
Palma de Mallorca, Illes Baleares, Spain, 07010
Reus, Tarragona, Spain, 43204
A Coruña, Spain, 15006
Barcelona, Spain, 08003
Barcelona, Spain, 08025
Barcelona, Spain, 08036
Barcelona, Spain, 08035
Lleida, Spain, 25198
Madrid, Spain, 28033
Madrid, Spain, 28034
Madrid, Spain, 28040
Madrid, Spain, 28041
Madrid, Spain, 28050
Palma de Mallorca, Spain, 07198
Sevilla, Spain, 41013
Sevilla, Spain, 41071
Valencia, Spain, 46014
Valencia, Spain, 46010
Valencia, Spain, 46009
Sweden
Kalmar, Sweden, 391 85
Stockholm, Sweden, 118 83
Stockholm, Sweden, 171 76
United Kingdom
Truro, Cornwall, United Kingdom, TR1 3LJ
Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
London, United Kingdom, NW3 2QG
Manchester, United Kingdom, M20 4BX
Northwood, United Kingdom, HA6 2RN
Sponsors and Collaborators
Bayer
Onyx Therapeutics, Inc.
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01234337     History of Changes
Other Study ID Numbers: 12444  2010-018501-10 
Study First Received: October 4, 2010
Results First Received: May 10, 2015
Last Updated: May 6, 2016
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria : Federal Ministry for Labour, Health, and Social Affairs
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Brazil: Ministry of Health
Canada: Health Canada
Chile: Comisión Nacional de Investigación Científica y Tecnológica
China: Ministry of Health
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: Ministry of Health and Welfare
Hungary: National Institute of Pharmacy
Ireland: Irish Medicines Board
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Japan: Ministry of Health, Labor and Welfare
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Bayer:
Breast Cancer
HER2-neu

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Capecitabine
Sorafenib
Niacinamide
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 28, 2016