E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Postmenopausal female subjects with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer, who have progressed on an aromatase inhibitor (AI) |
Mujeres con cáncer de mama metastásico, post-menopáusicas, con receptores estrogénicos positivos (ER+), receptor del factor de crecimiento epidérmico humano 2 negativo (HER-2-), que han progresado durante el tratamiento con un inhibidor de la aromatasa (IA). |
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E.1.1.1 | Medical condition in easily understood language |
Females who are post-menopause with a breast cancer that has spread to other part of the body, and that is estrogen receptor-positive and human epidermal growth factor receptor 2-negative |
Mujeres post-menopáusicas con cáncer de mama que se ha extendido a otras partes del cuerpo, con receptores estrogénicos positivos y receptor del factor de crecimiento epidérmico humano 2 negativo |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006315 |
E.1.2 | Term | Breast tumor malignant |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006204 |
E.1.2 | Term | Breast carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006283 |
E.1.2 | Term | Breast neoplasm malignant female |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10070575 |
E.1.2 | Term | Estrogen receptor positive breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006187 |
E.1.2 | Term | Breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of CC-486 in combination with fulvestrant relative to fulvestrant monotherapy, by estimation of the hazard ratio of progression free survival (PFS) |
El objetivo principal del estudio es evaluar la eficacia de CC-486 en combinación con fulvestrant, en comparación con fulvestrant en monoterapia, mediante la estimación de la razón de riesgos instantáneos de la supervivencia sin progresión (SSP). |
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E.2.2 | Secondary objectives of the trial |
?To estimate response rate (RR), clinical benefit rate (CBR), overall survival (OS), and duration of response (DOR) in all treatment arms ?To evaluate the safety of all treatment arms |
? Calcular la tasa de respuesta (TR), la tasa de beneficio clínico (TBC), la supervivencia global (SG) y la duración de la respuesta (DR) en todos los brazos de tratamiento. ? Evaluar la seguridad en todos los brazos de tratamiento. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subject is female >=18 years of age (at the time of signing the informed consent form) with metastatic breast cancer not amenable to curative treatment by surgery or radiotherapy. -Subject is considered postmenopausal -Subject has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive breast cancer by local laboratory (based on most recently analyzed biopsy). -Subject has human epidermal growth factor receptor 2 negative (HER2-) breast cancer (based on most recently analyzed biopsy) defined as a negative in situ hybridization test or an Immunohistochemistry (IHC) status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing. -Subject had disease refractory to an AI -Subject has an Eastern Cooperative Oncology Group ( ECOG) performance status of 0-1. - Subject has radiological documented measurable disease (ie, at least one measureable lesion as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1). ?If no measurable disease is present, then at least one predominantly lytic bone lesion must be present -Subject has adequate organ function. -Subject has adequate bone marrow function. |
1. Ser mujer de edad >= 18 años (en el momento de firmar el consentimiento informado) y presentar un cáncer de mama metastásico para el que no existe tratamiento curativo mediante cirugía o radioterapia. 2. Estar considerada post-menopáusica 3. Tener un diagnóstico de cáncer de mama con receptores estrogénicos positivos confirmado por métodos histológicos y/o citológicos en el laboratorio local (a partir de la última biopsia analizada). 4. Tener un cáncer de mama HER-2 negativo (a partir de la última biopsia analizada), definido por un resultado negativo en el análisis mediante hibridación in situ o un resultado de 0, 1+ o 2+ mediante IHQ. Si el resultado de la IHQ es 2+, se necesita un resultado negativo en otra prueba de hibridación in situ (FISH, CISH o SISH) efectuada en el laboratorio local. 5. Tener un tumor resistente al tratamiento con IA 6. Presentar un estado funcional del ECOG de 0 o 1. 7. Tener enfermedad mensurable documentada radiológicamente (es decir, al menos una lesión mensurable según los RECIST, versión 1.1). ? En ausencia de enfermedad mensurable, debe haber al menos una lesión ósea predominantemente lítica. 8. Funciones orgánicas adecuadas 9. Función medular adecuada |
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E.4 | Principal exclusion criteria |
-Subject has received > 1 prior line of chemotherapy in the metastatic setting -Subject has received any chemotherapy within 21 days prior to randomization. -Subject has received prior treatment with fulvestrant. -Subject has been previously treated with azacitidine (any formulation), decitabine, or any other hypomethylating agent. -Subject has a history of, or current symptomatic brain metastasis. -Subject has severe renal impairment (creatinine clearance < 30 ml/min). - Subject has an impaired ability to swallow oral medication. -Subject has a contraindication to receiving IM injections (eg, bleeding disorders, anticoagulant use). -Subject has significant active cardiac disease within the previous 6 months including unstable angina or angina requiring surgical or medical intervention, significant cardiac arrhythmia, or New York Heart Association (NYHA) class 3 or 4 congestive heart failure. -Subject is a female of Childbearing Potential [defined as a sexually mature woman who (1) has not undergone hysterectomy (the surgical removal of the uterus) or bilateral oopherectomy (the surgical removal of both ovaries) or (2) has not been naturally postmenopausal for at least 12 consecutive months (ie, has had menses at any time during the preceding 12 consecutive months)]. |
1. Haber recibido más de una línea de quimioterapia en el contexto de enfermedad metastásica. 2. Haber recibido cualquier quimioterapia en los 21 días previos a la aleatorización. 3. Tratamiento previo con fulvestrant. 4. Tratamiento previo con azacitidina (cualquier formulación), decitabina u otro fármaco hipometilante. 5. Antecedentes o presencia de metástasis cerebrales sintomáticas. 6. Insuficiencia renal grave (aclaramiento de creatinina < 30 ml/min). 7. Alteración de la capacidad de tragar medicación oral. 8. Contraindicación para recibir inyecciones IM (por ejemplo, trastornos hemorrágicos, tratamiento anticoagulante). 9. Presencia de una cardiopatía activa importante en los 6 meses precedentes, como angina inestable o angina con necesidad de intervención quirúrgica o médica, arritmia cardíaca significativa o insuficiencia cardíaca congestiva en clase 3 o 4 de la New York Heart Association (NYHA). 10. Mujeres en edad fértil [definidas como las sexualmente maduras que: 1) no se hayan sometido a una histerectomía (resección quirúrgica del útero) ni una ovariectomía bilateral (resección quirúrgica de ambos ovarios) o 2) no hayan presentado un estado posmenopáusico natural durante al menos 12 meses consecutivos (es decir, han tenido la menstruación en algún momento durante los 12 meses previos consecutivos)]. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Estimation of the hazard ratio of PFS of the combination arm relative to fulvestrant monotherapy arm |
Estimación de la razón de riesgos instantáneos de la SSP del brazo de tratamiento combinado en comparación con el brazo del monoterapia con fulvestrant. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
approximately 28 months after the start of enrollment |
aproximadamente 28 meses desde el inicio del reclutamiento |
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E.5.2 | Secondary end point(s) |
?ORR: the combined incidence of CR and PR, based on RECIST Version 1.1 ?Clinical benefit rate (CBR) : [Complete response (CR) + PR + SD ( >= 24 weeks)] ?Overall Survival (OS): time from date of randomization to date of death due to any cause ?Duration of response in subjects with objective CR or PR ?Safety: incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), Grade 3 and higher AEs, AEs of special interest, and laboratory abnormalities and other safety parameters |
? Tasa de respuesta objetiva (TRO): incidencia combinada de respuestas completas (RC) y respuestas parciales (RP) conforme a los RECIST, versión 1.1. ? Tasa de beneficio clínico (TBC): [RC + RP + EE (>= 24 semanas)]. ? Supervivencia global (SG): tiempo transcurrido desde la aleatorización hasta la fecha de muerte por cualquier causa. ? Duración de la respuesta (DR) en pacientes con RC o RP objetiva. ? Seguridad: incidencia de acontecimientos adversos aparecidos durante el tratamiento (AAAT), acontecimientos adversos graves (AAG), AA de grado 3 o superior, AA de especial interés y anomalías analíticas y otros parámetros de seguridad. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
?ORR: approximately 28 months after the start of enrollment ?CBR: approximately 28 months after the start of enrollment ?OS: approximately 28 months after the start of enrollment ?Duration of response: approximately 28 months after the start of enrollment ?Safety: Continuous starting after signature of informed consent document, until 28 days after treatment discontinuation |
?TRO: aproximadamente 28 meses desde el inicio del reclutamiento ?TBC: aproximadamente 28 meses desde el inicio del reclutamiento ?SG: aproximadamente 28 meses desde el inicio del reclutamiento ?Duración de la respuesta: aproximadamente 28 meses desde el inicio del reclutamiento ?Seguridad: Inicio justo después de la firma del documento de consentimiento informado, hasta 28 días después de la interrupción del tratamiento |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
France |
Italy |
Spain |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The End of Trial is defined as either the date of the last visit of the last subject to complete the study, or the date of receipt of the last data point from the last subject that is required for primary, secondary, and/or exploratory analysis as pre-specified in the protocol whichever is the later date |
El final del ensayo se define como la fecha de la última visita de la última paciente que complete el seguimiento de la seguridad posterior al tratamiento o la fecha de recepción del último punto de datos de la última paciente que se precise para análisis principal preestablecida en el protocolo o en el plan de análisis estadístico (PAE), lo que ocurra antes. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |