Resumen

El objetivo de este ensayo clínico de fase III es comparar la eficacia y seguridad de sorafenib en combinación con capecitabina versus capecitabina en combinación con placebo en el tratamiento de sujetos con cáncer de mama HER2-negativo localmente avanzado o metastásico, que son resistentes o han fracasado a un taxano previo y a una antraciclina, o para quienes no está indicada terapia adicional con antraciclinas. Tras la firma del consentimiento informado pueden transcurrir hasta 28 días antes de iniciar el tratamiento, durante los cuales se realizarán una serie de pruebas que incluirán evaluaciones tumorales e historia clínica. Las siguientes pruebas y evaluaciones deberán realizarse dentro de los 7 días previos al inicio del tratamiento, el Día 1 de cada ciclo y al finalizar el estudio: electrocardiograma, análisis de sangre, cuestionarios de calidad de vida del paciente, examen físico completo y signos vitales. El tratamiento se administrará en ciclos de 21 días, con sorafenib/placebo tomado todos los días durante 21 días y capecitabina durante los primeros 14 días. Los pacientes acudirán semanalmente durante las primeras 6 semanas y luego el Día 1 de cada ciclo a partir de los primeros 2 ciclos. Durante las visitas semanales, los sujetos serán evaluados por posibles efectos secundarios y se realizarán extracciones de sangre para el estudio el Día 1 de cada ciclo. Se realizará seguimiento de los sujetos en cuanto a supervivencia global.

Descripción detallada

Resumen de investigación (NRES, Reino Unido): El cáncer de mama es el cáncer más frecuentemente diagnosticado en mujeres y la principal causa de muerte relacionada con el cáncer entre mujeres a nivel mundial. Sin embargo, a pesar de los avances en el tratamiento de la enfermedad en estadio temprano, aproximadamente el 25-40% de las pacientes desarrollará recurrencia o diseminación a otras partes del cuerpo, lo cual es en gran medida incurable. La supervivencia promedio de las pacientes con cáncer de mama que se ha diseminado a otras partes del cuerpo (metástasis) es de 2 a 3 años tras el diagnóstico, y aunque existen varias opciones de tratamiento, incluidos diversos agentes de quimioterapia, no existe un único estándar de atención. El fármaco en estudio (sorafenib) actúa inhibiendo ciertas vías en el organismo que contribuyen al crecimiento tumoral y a la formación de nuevos vasos sanguíneos (angiogénesis). La angiogénesis desempeña un papel importante en el desarrollo, transformación y diseminación del cáncer de mama. Capecitabina es un fármaco de quimioterapia aprobado para pacientes cuyo cáncer de mama se ha diseminado a otras partes del cuerpo (metastásico) y no responde a otras clases de fármacos de quimioterapia. Los datos de un estudio clínico de fase IIb sugieren que existe un rol para la combinación de sorafenib y capecitabina en el tratamiento del cáncer de mama localmente avanzado o metastásico. Los pacientes en este estudio confirmatorio de fase III serán asignados aleatoriamente para recibir: * Capecitabina + sorafenib * Capecitabina + placebo ("medicamento ficticio" sin principio activo) Los participantes continuarán recibiendo los tratamientos hasta que se produzca progresión radiográfica o clínica de la enfermedad, efectos secundarios que requieran su retirada, embarazo, incumplimiento del protocolo o retirada del consentimiento. Por lo tanto, la duración de la participación variará para cada individuo. Se espera que este estudio cierre el 31 de marzo de 2013. Este es un estudio multicéntrico que se llevará a cabo en Europa, América del Norte y del Sur, Asia, Australia y Sudáfrica. Se prevé reclutar aproximadamente 519 participantes a nivel mundial.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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

Criterios de exclusión

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

Intervenciones

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

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,

Ensayo Clínico de Fase III, Aleatorizado, Doble Ciego, Controlado con Placebo que Compara Capecitabina más Sorafenib versus Capecitabina más Placebo en el Tratamiento del Cáncer de Mama HER2-Negativo Localmente Avanzado o Metastásico

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Sorafenib (Nexavar, BAY43-9006)

Placebo

Capecitabine

Ubicaciones

Patrocinadores