E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hormone receptor-positive, HER2-negative, early breast cancer. |
Cáncer de mama precoz con receptores hormonales positivos, HER2 negativo. |
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E.1.1.1 | Medical condition in easily understood language |
Early breast cancer. |
Cáncer de mama precoz. |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006203 |
E.1.2 | Term | Breast cancer stage unspecified |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
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 | 100000004864 |
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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 compare iDFS for ribociclib + ET versus ET in patients with HRpositive, HER2-negative, EBC. |
Comparar la supervivencia libre enfermedad invasiva (SLEi ) de ribociclib + terapia endocrina (TE) comparado a terapia endocrina (TE) en pacientes con cáncer de mama precoz (CMP), receptores hormonales (RH) positivos, HER2 negativo. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the two treatment arms with respect to recurrence-free survival (RFS). 2. To evaluate the two treatment arms with respect to distant diseasefree survival (DDFS). 3. To evaluate the two treatment arms with respect to OS. 4. To evaluate patient reported outcomes (PRO) for health-related quality of life (QoL) in the two treatment arms. 5. To characterize the PK of ribociclib when given in combination with NSAI (and goserelin if applicable). |
1. Evaluar en los dos brazos de tratamiento la supervivencia libre de recaída (SLR). 2. Evaluar en los dos brazos de tratamiento la supervivencia libre de enfermedad a distancia (SLED). 3. Evaluar en los dos brazos de tratamiento la supervivencia global (SG). 4. Evaluar los resultados comunicados por el paciente (PROs, de las siglas en inglés, Patient Reported Outcomes) relacionados con la salud a través de los cuestionarios de calidad de vida (CdV) en los dos brazos de tratamiento. 5. Caracterizar la farmacocinética (FC) de ribociclib al administrarse en combinación con un IANE (y goserelina, si procede). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patient is ≥ 18 years-old at the time of PICF signature. - Patient is female with known menopausal status at the time of PICF signature or initiation of adjuvant ET (whichever occurs earlier), or male. - Patient with histologically confirmed unilateral primary invasive adenocarcinoma of the breast with a date of initial cytologic or histologic diagnosis within 18 months prior to randomization. - Patient has breast cancer that is positive for ER and/or PgR. - Patient has HER2-negative breast cancer. - Patient has available archival tumor tissue from the surgical specimen. - Patient after surgical resection where tumor was removed completely, with the final surgical specimen microscopic margins free from tumor, and who belongs to one of the following categories (anatomic stage group II or III). - If indicated, patient has completed adjuvant and/or neoadjuvant chemotherapy according to the institutional guidelines. - If indicated, patient has completed adjuvant radiotherapy according to the institutional guidelines. - Patient has no contraindication for the adjuvant ET in the trial and is planned to be treated with ET for 5 years. |
- Paciente ≥ 18 años en el momento de firmar la Hoja de información y consentimiento informado del paciente (HICIP). - Mujer con menopausia conocida en el momento de firmar la HICIP o de iniciar la TE adyuvante (lo que ocurra en primer lugar), o varón. - Paciente con adenocarcinoma mamario primario infiltrante y unilateral, confirmado histológicamente, con fecha de diagnóstico citológico o histológico inicial dentro de los 18 meses anteriores a la aleatorización. - Paciente con cáncer de mama positivo para RE y/o RPg. - Paciente con cáncer de mama HER2 negativo. - Paciente con tejido tumoral archivado, procedente de una pieza quirúrgica. - Paciente sometida a resección quirúrgica en la que el tumor fue resecado completamente, con márgenes microscópicos de la pieza quirúrgica final libres de tumor, y perteneciente a una de las siguientes categorías (estadio anatómico II o III). - Si estaba indicada, el paciente tiene que haber finalizado la quimioterapia adyuvante y/o neoadyuvante de acuerdo con los protocolos del centro. - Si estaba indicada, el paciente tiene que haber finalizado la radioterapia adyuvante de acuerdo con los protocolos del centro. - El paciente no presenta ninguna contraindicación para la TE adyuvante del ensayo y se ha programado que reciba TE durante 5 años. |
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E.4 | Principal exclusion criteria |
- Patient has received any CDK4/6 inhibitor. - Patient has received prior treatment with tamoxifen, raloxifene or AIs for reduction in risk (“chemoprevention”) of breast cancer and/or treatment for osteoporosis within the last 2 years prior to PICF signature. - Patient has received prior treatment with anthracyclines at cumulative doses of 450 mg/m² or more for doxorubicin, or 900 mg/m² or more for epirubicin. - Patient with a known hypersensitivity to any of the excipients of ribociclib and/or ET. - Patient with distant metastases of breast cancer beyond regional lymph nodes (stage IV according to AJCC 8th edition) and/or evidence of recurrence after curative surgery. - Patient is concurrently using other anti-neoplastic therapy with the exception of adjuvant ET. - Patient has had major surgery, chemotherapy or radiotherapy within 14 days prior to randomization. - Patient has not recovered from clinical and laboratory acute toxicities related to prior anti-cancer therapies. - Patient has a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed within 2 years before PICF signature. - Patient has known HIV infection, Hepatitis B or C infection. - Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality. - Patient is currently receiving any of the following substances within 7 days before randomization: Concomitant medications, herbal supplements, and/or fruits that are known as strong inhibitors or inducers of CYP3A4/5 or Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5. - Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting trial treatment. - Patient has impairment of GI function or GI disease that may significantly alter the absorption of the oral trial treatments. - Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator’s judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical trial or compromise compliance with the protocol. - Patient participated in another interventional study and received treatment with an investigational product (or used an investigational device) within 30 days prior to randomization or within 5 half-lives of the investigational product, whichever is longer. - Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the trial.
Additional exclusion criteria as per full protocol may apply. |
- Paciente que ha recibido algún inhibidor de CDK4/6. - Paciente que ha recibido tratamiento previo con tamoxifeno, raloxifeno o un IA para la reducción del riesgo de cáncer de mama (“quimioprevención”) y/o tratamiento de la osteoporosis dentro de los 2 años anteriores a la firma de la HICIP. - Paciente que ha recibido tratamiento previo con antraciclinas, con dosis acumuladas de 450 mg/m² o más de doxorrubicina, o de 900 mg/m² o más de epirrubicina. - Paciente con hipersensibilidad conocida a cualquiera de los excipientes de ribociclib y/o de la TE. - Paciente con metástasis a distancia del cáncer de mama, más allá de los ganglios linfáticos regionales (estadio IV según la clasificación del AJCC, 8ª edición) y/o evidencia de recaída después de una intervención quirúrgica con intención curativa. - Paciente que recibe simultáneamente otro tratamiento antineoplásico, con la excepción de la TE adyuvante. - Paciente sometido a una cirugía mayor, quimioterapia o radioterapia dentro de los 14 días anteriores a la aleatorización. - Paciente no recuperado de las toxicidades agudas clínicas o analíticas relacionadas con tratamientos antineoplásicos previos. - Paciente con neoplasia maligna infiltrante concurrente o neoplasia maligna infiltrante anterior cuyo tratamiento haya finalizado en los 2 años anteriores a la firma de la HICIP. - Paciente con antecedentes conocidos de infección por el virus de la inmunodeficiencia humana (VIH), hepatitis B (VHB) o de la hepatitis C (VHC). - Patología cardiaca no controlada y clínicamente significativa y/o alteración de la repolarización cardiaca. - El paciente está recibiendo actualmente alguna de las siguientes sustancias, en los 7 días anteriores a la aleatorización: Medicación concomitante, suplementos de plantas medicinales y/o frutas o sus zumos, conocidos por ser potentes inhibidores o inductores del CYP3A4/5 o Medicamentos con un estrecho margen terapéutico que se metabolizan predominantemente a través del CYP3A4/5. - Paciente que actualmente recibe o ha recibido corticoides sistémicos ≤ 2 semanas antes de iniciar el tratamiento del ensayo. - Paciente con deterioro de la función gastrointestinal (GI) o una enfermedad digestiva que pueda alterar de forma importante la absorción de los tratamientos orales del ensayo. - Paciente que presenta cualquier otra patología médica grave y/o no controlada concurrente que, en opinión del investigador, podría causar riesgos inaceptables para la seguridad, contraindica la participación del paciente en el ensayo clínico, compromete el cumplimiento del protocolo. - Paciente que haya participado en otro estudio intervencionista y haya recibido tratamiento con un producto en investigación (o usado un dispositivo en investigación) dentro de los 30 días anteriores a la aleatorización o dentro de 5 semividas del producto en investigación, lo que sea más prolongado. - Mujer embarazada o en periodo de lactancia, o mujer que planea quedarse embarazada o amamantar a un bebé durante el ensayo.
Pueden aplicar criterios de exclusión adicionales según el protocolo completo. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
iDFS using STEEP criteria, as assessed by Investigator. |
Supervivencia libre enfermedad invasiva (SLEi) utilizando los criterios STEEP (Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials), según la evaluación del Investigador. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Recurrence free survival (RFS) using STEEP criteria (Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials). - Distant disease free survival (DDFS) using STEEP criteria (Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials). - Overall survival (OS). - Change from baseline in the physical functioning subscale score and global health status/Quality of life scale score as assessed by EORTC QLQ-C30. - PK parameters such as Cmax, Tmax, and AUC 0- 24h for ribociclib. |
- Supervivencia libre de recaída (SLR) utilizando los criterios STEEP (Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials). - Supervivencia libre de enfermedad a distancia (SLED) utilizando los criterios STEEP (Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials). - Supervivencia global (SG). - Cambio respecto al momento basal en la puntuación de la subescala de funcionamiento físico y en la puntuación de la escala de situación global de salud/CdV, evaluado mediante el cuestionario EORTC QLQ-C30. - Parámetros Farmacocinéticos de ribociclib, como Cmax, Tmax, y AUC 0-24h. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- 3.5 years. - 3.5 years. - 7.5 years. - 3.5 years. - 3.5 years. |
- 3,5 años. - 3,5 años. - 7,5 años. - 3,5 años. - 3,5 años. |
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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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
- Quality of life (QoL) and patient reported outcomes (PRO). |
- Calidad de vida (CdV) y resultados comunicados por el paciente (PROs, de las siglas en inglés, Patient Reported Outcomes). |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 35 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 201 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
China |
France |
Germany |
Hungary |
Ireland |
Italy |
Korea, Republic of |
Peru |
Poland |
Romania |
Russian Federation |
Spain |
Taiwan |
United Kingdom |
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
|
End of trial will be declared when 60 months + 30 days have elapsed from the date the last patient has been randomized. |
El final del ensayo se declarará cuando hayan transcurrido 60 meses + 30 días a partir de la fecha en que el último paciente haya sido asignado al azar. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial days | 4 |