Trial Condition(s):

Breast Cancer

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

Bayer Identifier:

12444

ClinicalTrials.gov Identifier:

NCT01234337

EudraCT Number:

2010-018501-10

Study Completed

Trial 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.

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

Trial Summary

Enrollment Goal
537
Trial Dates
black-arrow
Phase
3
Could I receive a placebo?
Yes
Products
Nexavar (Sorafenib, BAY43-9006)
Accepts Healthy Volunteers
No

Where to Participate

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Locations
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Memphis, United States, 38120

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Completed
 
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Greenbrae, United States, 94904-2007

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Petah Tikva, Israel, 4941492

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Jerusalem, Israel, 9372212

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Albuquerque, United States, 87131

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Mar del Plata, Argentina, B7600CTO

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West Palm Beach, United States, 33407

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BRUGGE, Belgium, 8000

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HASSELT, Belgium, 3500

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BRUXELLES - BRUSSEL, Belgium, 1000

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LIEGE, Belgium, 4000

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Madrid, Spain, 28034

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Madrid, Spain, 28033

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Madrid, Spain, 28040

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Barcelona, Spain, 08003

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Barcelona, Spain, 08025

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Barcelona, Spain, 08035

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Terrassa, Spain, 08221

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Lleida, Spain, 25198

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Valencia, Spain, 46009

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Valencia, Spain, 46014

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Palma de Mallorca, Spain, 07198

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Reus, Spain, 43204

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EDEGEM, Belgium, 2650

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Bunkyo, Japan, 113-8677

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Kita-Adachigun, Japan, 362-0806

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Hidaka, Japan, 350-1298

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Nagoya, Japan, 464-8681

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Matsuyama, Japan, 791-0280

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Chiba, Japan, 260-8717

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Fukuoka, Japan, 811-1395

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Suita, Japan, 565-0871

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Koto-ku, Japan, 135-8550

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Osaka, Japan, 540-0006

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Beer Sheva, Israel, 8410101

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Haifa, Israel, 3109601

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Haifa, Israel, 35152

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Jerusalem, Israel, 9112001

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Dublin, Ireland, DUBLIN 4

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Cork, Ireland

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Modena, Italy, 41124

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Milano, Italy, 20089

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Forlì-Cesena, Italy, 47014

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Ancona, Italy, 60126

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Pisa, Italy, 56126

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Bologna, Italy, 40138

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Palermo, Italy, 90127

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Cremona, Italy, 26100

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Ravenna, Italy, 48121

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Wien, Austria, 1100

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Linz, Austria, 4010

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A Coruña, Spain, 15006

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Erlangen, Germany, 91054

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Mainz, Germany, 55131

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Stendal, Germany, 39576

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Gdansk, Poland, 80-952

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Poznan, Poland, 61-485

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Gdynia, Poland, 81-519

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Praha 5, Czech Republic, 150 30

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Praha 5, Czech Republic, 150 06

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Olomouc, Czech Republic, 775 20

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Chelyabinsk, Russia, 454087

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Castellón de la Plana, Spain, 12002

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Szentes, Hungary, 6600

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Pecs, Hungary, 7624

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Budapest, Hungary, 1032

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Szolnok, Hungary, H-5004

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Nyiregyhaza, Hungary, H-4400

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Ramat Gan, Israel, 5266202

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Nantes, France, 44805

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Lille, France, 59020

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Roma, Italy, 00161

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Sevilla, Spain, 41013

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Sevilla, Spain, 41071

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Valencia, Spain, 46010

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Madrid, Spain, 28041

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Santiago de Compostela, Spain, 15706

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Liverpool, Australia, 2170

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Perth, Australia, 6000

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Garran, Australia, 2605

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Frankston, Australia

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Waratah, Australia, 2298

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Athens, Greece, 11528

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Heraklion, Greece, 711 10

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Larissa, Greece, 41100

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Ioannina, Greece, 45500

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Patras, Greece, 26500

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London, United Kingdom, NW3 2QG

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Northwood, United Kingdom, HA6 2RN

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Nottingham, United Kingdom, NG5 1PB

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Manchester, United Kingdom, M20 4BX

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Truro, United Kingdom, TR1 3LJ

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TOULOUSE, France, 31052

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Pretoria, South Africa, 0181

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Johannesburg, South Africa, 2196

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Pretoria, South Africa, 0081

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Praha 10, Czech Republic, 10034

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Ceske Budejovice, Czech Republic, 370 01

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Nymburk, Czech Republic, 288 02

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Kazan, Russia, 420029

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Dublin, Ireland, DUBLIN 8

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Boston, United States, 02114

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Lake Success, United States, 11042

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Madison, United States, 53792

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Sylmar, United States, 91342

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Durham, United States, 27710

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Buenos Aires, Argentina, C1280AEB

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Buenos Aires, Argentina, C1425AWC

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Bendigo, Australia, 3550

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Adelaide, Australia, 5000

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Completed
 
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Berlin, Germany, 13589

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Completed
 
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Monza-Brianza, Italy, 20900

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Completed
 
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Investigative Site

Palma de Mallorca, Spain, 07120

Status
Completed
 
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Investigative Site

Sabadell, Spain, 08208

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Completed
 
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Investigative Site

Pretoria, South Africa, 0084

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Completed
 
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Praha 2, Czech Republic, 128 08

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Completed
 
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Investigative Site

Galway, Ireland

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Completed
 
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Investigative Site

Leipzig, Germany, 04103

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Completed
 
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Investigative Site

Montreal, Canada, H2L 4M1

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Completed
 
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Investigative Site

Dublin, Ireland, 9

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Completed
 
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Köln, Germany, 51067

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Completed
 
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Investigative Site

Barcelona, Spain, 08036

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Completed
 
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Springfield, United States, 65804

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Completed
 
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San Juan, United States, 00918

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Completed
 
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Evansville, United States, 47713

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Montreal, Canada, H3G 1A4

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Louisville, United States, 40207

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Bristol, United States, 37620

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Completed
 
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Joliet, United States, 60435

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Completed
 
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Investigative Site

Philadelphia, United States, 19104

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Completed
 
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Investigative Site

El Paso, United States, 79905

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Completed
 
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Investigative Site

Burlington, United States, 05405

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Completed
 
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Investigative Site

Frankfurt, Germany, 60389

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Completed
 
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Investigative Site

Offenbach, Germany, 63069

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Completed
 
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Investigative Site

Jackson, United States, 39202

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Completed
 
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CLERMONT FERRAND CEDEX 1, France, 63011

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Completed
 
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SAINT CLOUD, France, 92210

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Completed
 
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Investigative Site

Dublin, Ireland, 7

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Completed
 
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Investigative Site

Dublin, Ireland, 7

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Completed
 
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Investigative Site

Stockholm, Sweden, 171 76

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Completed
 
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Investigative Site

Köln, Germany, 50931

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Completed
 
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Investigative Site

Port Elizabeth, South Africa, 6045

Status
Completed
 
Locations

Investigative Site

Nova Ves Pod Plesi, Czech Republic, 262 04

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Completed
 
Locations

Investigative Site

Stockholm, Sweden, 118 83

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Completed
 
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Investigative Site

Boston, United States, 02115-6084

Status
Completed
 
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Investigative Site

Beijing, China, 100021

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Completed
 
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Investigative Site

Beijing, China, 100071

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Completed
 
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Investigative Site

Shenyang, China, 110001

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Completed
 
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Investigative Site

Tianjin, China, 300060

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Completed
 
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Investigative Site

Shanghai, China, 200030

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Completed
 
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Nanning, China, 530021

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Completed
 
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Investigative Site

Xi'an, China, 710032

Status
Completed
 
Locations

Investigative Site

Madrid, Spain, 28050

Status
Completed
 
Locations

Investigative Site

Kagoshima, Japan, 892-0833

Status
Completed
 

Trial Design