E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Early or locally advanced/inflammatory HER2-positive (HER2+) breast cancer. |
Cáncer de mama HER2 positivo (HER2+) temprano o localmente avanzado/inflamatorio. |
|
E.1.1.1 | Medical condition in easily understood language |
Early or locally advanced HER2-positive (HER2+) breast cancer. |
Cáncer de mama HER2 positivo (HER2+) temprano o localmente avanzado. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 patient preference of pertuzumab and trastuzumab (PH) fixed-dose combination (FDC) for subcutaneous (SC) administration in the home setting during the cross-over period of the adjuvant phase of the study |
Evaluar la preferencia del paciente por la administración de PH FDC SC en el entorno domiciliario durante el período de tratamiento adyuvante cruzado del estudio |
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E.2.2 | Secondary objectives of the trial |
● To evaluate the perception of healthcare professionals (HCPs) of time/resource use and convenience of PH FDC SC compared to PH IV during the neoadjuvant phase of the study ● Collect pathological complete response (pCR) data post-surgery ● To evaluate Health-related Quality of Life (HRQoL) during the neoadjuvant phase of the study and ● With PH FDC SC administered during the adjuvant phase of the study ● Evaluate the perception of HCPs of time/resource use of PH FDC SC during adjuvant cross-over period ● Evaluate HRQoL for participants treated with trastuzumab emtansine IV during the adjuvant phase ● Evaluate the safety and tolerability of PH FDC SC and P+H IV during neoadjuvant phase of the study ● Evaluate the safety and tolerability of PH FDC SC administered in the home setting and hospital setting during the cross-over period and the entire adjuvant treatment period ● Evaluate the safety and tolerability of trastuzumab emtansine IV during the adjuvant phase of the study |
- Evaluar percepción de los PS respecto al tiempo/uso de recursos y la comodidad de PH FDC SC en comparación con pertuzumab IV y trastuzumab IV (P+H IV) durante la fase de tto neoadyuvante - Recoger datos sobre resp patológica completa (RpC) después cirugía - Evaluar calidad vida relac con la salud (CdVRS) durante fase tto neoadyuvante - Evaluar lCdVRs con PH FDC SC admin durante la fase de tto adyuvante - Evaluar percepción de los PS respecto al tiempo/uso de recursos con el PH FDC SC durante el período tto adyuvante cruzado - Evaluar CdVRs de los participantes tratados con trastuzumab emtansina IV durante fase tto adyuvante -Evaluar seguridad y la tolerabilidad de PH FDC SC y P+H IV durante fase tto neoadyuvante - Evaluar seguridad y tolerabilidad de PH FDC SC admin en entorno domiciliario y hospitalario durante período tto cruzado y todo el período tto adyuvante - Evaluar seguridad y tolerabilidad de trastuzumab emtansina IV durante la fase de tto adyuvante |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
● Age >= 18 years ● Eastern Cooperative Oncology Group (ECOG) performance status 0-1 ● Intact skin at planned site of SC injections ● Left ventricular ejection fraction (LVEF) >= 55% by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) ● Negative human immunodeficiency virus (HIV) test at screening ● Negative hepatitis B surface antigen (HBsAg) test at screening ● Positive hepatitis B surface antibody (HBsAb) test at screening ● Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening ● For female participants of childbearing potential: agreement to remain abstinent or use contraception and agree to refrain from donating eggs during the treatment period and for 7 months after the final dose of the study treatment ● For male participants: agreement to remain abstinent or use a condom, and agree to refrain from donating sperm during the treatment period and for 7 months after the final dose of study treatment to avoid exposing the embryo Disease-specific Inclusion Criteria ● Female and male participants with stage II-IIIC early or locally advanced/inflammatory HER2+ breast cancer. ● Primary tumor > 2 cm in diameter, or node-positive disease ● HER2+ breast cancer confirmed by a local laboratory prior to study enrollment ● Hormone receptor status of the primary tumor determined by local assessment following American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines and updates ● Agreement to undergo mastectomy or breast conserving surgery after neoadjuvant therapy, including the axillary nodes ● Availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue block for local confirmation of HER2 and hormone receptor status following current ASCO/CAP guidelines Inclusion Criteria for Treatment with Adjuvant PH FDC SC ● Completed the neoadjuvant phase of this study and underwent surgery, and achieved Pathologic complete response (pCR), defined as eradication of invasive disease in the breast and axilla according to the current American Joint Committee on Cancer (AJCC) staging system classification, and using the resected specimen by the local pathologist on the basis of guidelines to be provided in a Pathology Manual ● Adequate wound healing after breast cancer surgery per investigator’s assessment to allow initiation of study treatment within =< 9 weeks of last systemic neoadjuvant therapy |
● Edad >= 18 años ●ECOG 0-1 ● Piel intacta en el lugar previsto para las inyecciones SC ● Fracción de eyección del ventrículo izquierdo (FEVI) >= 55 % por ecocardiograma (ECHO) o escaneo de adquisición con múltiples gatillos (MUGA) ● Prueba negativa del virus de la inmunodeficiencia humana (VIH) en la selección ● Prueba de antígeno de superficie de hepatitis B (HBsAg) negativa en la selección ● Prueba de anticuerpos de superficie de hepatitis B (HBsAb) positiva en la selección ● Prueba de anticuerpos contra el virus de la hepatitis C (VHC) negativa en la selección, o prueba de anticuerpos contra el VHC positiva seguida de una prueba de ARN del VHC negativa en la selección ● Para mujeres participantes en edad fértil: acuerdo de permanecer en abstinencia o usar métodos anticonceptivos y acuerdo de abstenerse de donar óvulos durante el período de tratamiento y durante los 7 meses posteriores a la dosis final del tratamiento del estudio. ● Para participantes masculinos: acuerdo de permanecer en abstinencia o usar un condón, y acuerdo de abstenerse de donar esperma durante el período de tratamiento y durante los 7 meses posteriores a la dosis final del tratamiento del estudio para evitar la exposición del embrión. Criterios de inclusión específicos de la enfermedad ● Participantes femeninos y masculinos con cáncer de mama HER2+ temprano o localmente avanzado/inflamatorio en estadio II-IIIC. ● Tumor primario > 2 cm de diámetro o enfermedad con ganglios positivos ● Cáncer de mama HER2+ confirmado por un laboratorio local antes de la inscripción en el estudio ● Estado del receptor hormonal del tumor primario determinado por evaluación local siguiendo las pautas y actualizaciones de la Sociedad Estadounidense de Oncología Clínica (ASCO)/Colegio Estadounidense de Patólogos (CAP) ● Acuerdo para someterse a una mastectomía o cirugía conservadora del seno después de la terapia neoadyuvante, incluidos los ganglios axilares ● Disponibilidad de bloques de tejido tumoral fijados en formalina e incluidos en parafina (FFPE) para la confirmación local del estado del receptor hormonal y HER2 siguiendo las pautas actuales de ASCO/CAP Criterios de Inclusión para Tratamiento con Adyuvante PH FDC SC ● Completó la fase neoadyuvante de este estudio y se sometió a cirugía, y logró una respuesta patológica completa (pCR, por sus siglas en inglés), definida como la erradicación de la enfermedad invasiva en la mama y la axila de acuerdo con la clasificación actual del sistema de estadificación del American Joint Committee on Cancer (AJCC), y usando el espécimen resecado por el patólogo local sobre la base de las pautas que se proporcionarán en un Manual de Patología ● Cicatrización adecuada de la herida después de la cirugía de cáncer de mama según la evaluación del investigador para permitir el inicio del tratamiento del estudio dentro de =< 9 semanas desde la última terapia neoadyuvante sistémica |
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E.4 | Principal exclusion criteria |
● Stage IV breast cancer ● History of concurrent or previously treated non-breast malignancies ● Participants who are pregnant or breastfeeding or intending to become pregnant during the study or within 7 months after the final dose of study treatments ● Treatment with investigational therapy within 28 days prior to initiation of study treatment ● Active, unresolved infections at screening requiring treatment ● Participants who may have had a recent episode of thromboembolism and are still trying to optimize the anticoagulation dose and/or have not normalized their International Normalized Ratio (INR) ● Serious cardiac illness or medical conditions ● History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias ● Inadequate bone marrow function ● Impaired liver function ● Renal function with creatinine clearance < 50 mL/min using the Cockroft-Gault formula and serum creatinine > 1.5 x Upper limit of normal (ULN) ● Major surgical procedure unrelated to breast cancer within 28 days prior to study entry or anticipation of the need for major surgery during the course of study treatment ● Current severe, uncontrolled systemic disease that may interfere with planned treatment ● Any serious medical condition or abnormality in clinical laboratory tests that precludes an individual's safe participation in and completion of the study ● Known active liver disease, for example, active viral hepatitis infection, autoimmune hepatic disorders, or sclerosing cholangitis ● Known hypersensitivity to any of the study drugs, excipients, and/or murine proteins or a history of severe allergic or immunological reactions, e.g., difficult to control asthma ● Current chronic daily treatment with corticosteroids ● Assessment by the investigator as being unable or unwilling to comply with the requirements of the protocol Cancer-specific Exclusion Criteria for Neoadjuvant Phase ● Participants who have received any previous systemic therapy for treatment or prevention of breast cancer, or radiation therapy for the treatment of cancer ● Participants who have a past history of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) if they have received any systemic therapy for its treatment or radiation therapy to the ipsi- or contralateral breast cancer ● Participants with high-risk for breast cancer who have received chemopreventive drugs in the past are not allowed to enter the study ● Participants with multicentric breast cancer, unless all tumors are HER2+ ● Participants with bilateral breast cancer ● Participants who have undergone an excisional biopsy of primary tumor and/or axillary lymph nodes ● Axillary lymph node dissection (ALND) prior to initiation of neoadjuvant therapy ● Sentinel lymph node biopsy (SLNB) prior to neoadjuvant therapy |
● Cáncer de mama en estadio IV ● Antecedentes de neoplasias malignas no mamarias concurrentes o tratadas previamente ● Participantes que están embarazadas o amamantando o que tienen la intención de quedar embarazadas durante el estudio o dentro de los 7 meses posteriores a la dosis final de los tratamientos del estudio ● Tratamiento con terapia en investigación dentro de los 28 días anteriores al inicio del tratamiento del estudio ● Infecciones activas no resueltas en la selección que requieren tratamiento ● Participantes que pueden haber tenido un episodio reciente de tromboembolismo y todavía están tratando de optimizar la dosis de anticoagulación y/o no han normalizado su Razón Internacional Normalizada (INR) ● Enfermedad cardíaca grave o condiciones médicas ● Antecedentes de arritmias ventriculares o factores de riesgo de arritmias ventriculares ● Función inadecuada de la médula ósea ● Deterioro de la función hepática ● Función renal con aclaramiento de creatinina < 50 ml/min utilizando la fórmula de Cockroft-Gault y creatinina sérica > 1,5 x límite superior de la normalidad (LSN) ● Procedimiento quirúrgico mayor no relacionado con el cáncer de mama dentro de los 28 días anteriores al ingreso al estudio o anticipación de la necesidad de una cirugía mayor durante el curso del tratamiento del estudio ● Enfermedad sistémica actual grave y no controlada que puede interferir con el tratamiento planificado ● Cualquier condición médica grave o anomalía en las pruebas de laboratorio clínico que impida la participación segura de una persona en el estudio y su finalización. ● Enfermedad hepática activa conocida, por ejemplo, infección por hepatitis viral activa, trastornos hepáticos autoinmunes o colangitis esclerosante ● Hipersensibilidad conocida a cualquiera de los fármacos del estudio, excipientes y/o proteínas murinas o antecedentes de reacciones alérgicas o inmunológicas graves, por ejemplo, asma difícil de controlar ● Tratamiento diario crónico actual con corticoides ● Evaluación por parte del investigador de que no puede o no quiere cumplir con los requisitos del protocolo Criterios de exclusión específicos del cáncer para la fase neoadyuvante ● Participantes que hayan recibido cualquier terapia sistémica previa para el tratamiento o la prevención del cáncer de mama, o radioterapia para el tratamiento del cáncer ● Participantes que tienen antecedentes de carcinoma ductal in situ (DCIS) o carcinoma lobulillar in situ (LCIS) si han recibido alguna terapia sistémica para su tratamiento o radioterapia para el cáncer de mama ipsi o contralateral ● Los participantes con alto riesgo de cáncer de mama que hayan recibido medicamentos quimiopreventivos en el pasado no pueden participar en el estudio. ● Participantes con cáncer de mama multicéntrico, a menos que todos los tumores sean HER2+ ● Participantes con cáncer de mama bilateral ● Participantes que se han sometido a una biopsia por escisión del tumor primario o de los ganglios linfáticos axilares ● Disección de ganglios linfáticos axilares (ALND) antes del inicio de la terapia neoadyuvante ● Biopsia de ganglio linfático centinela (SLNB) antes de la terapia neoadyuvante |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Proportion of participants who preferred the administration of PH FDC SC in the home setting compared with the hospital setting in Question 1 of Patient Preference Questionnaire (PPQ) |
1. Proporción de participantes que prefirieron la administración de PH FDC SC en el ámbito domiciliario en comparación con el ámbito hospitalario en la Pregunta 1 del Cuestionario de preferencia del paciente (PPQ) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. At the end of cross over period on Day 1, Cycle 8 of adjuvant phase |
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E.5.2 | Secondary end point(s) |
1. Responses of HCPs to the Healthcare Professional Questionnaire (HCPQ) by individual questions in the neoadjuvant phase 2. Proportion of participants achieving pCR, defined as eradication of invasive disease in the breast and axilla (i.e., ypT0/Tis ypN0), according to local pathologist assessment following the AJCC criteria 3. HRQoL assessed by European Organization for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ)-C30 scores in the neoadjuvant phase 4. HRQoL assessed by EORTC QLQ-C30 scores in the participants treated with PH FDC SC during the adjuvant phase 5. Responses of HCPs to the HCPQ by individual questions in the adjuvant cross-over period 6. HRQoL assessed by EORTC QLQ-C30 scores in the participants treated with trastuzumab emtansine IV during the adjuvant phase 7. Incidence, nature and severity of all Adverse events (AEs), Grade >= 3 AEs, Serious adverse event (SAEs), and cardiac AEs (including LVEF events) with severity determined according to National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) v5.0 8. Incidence of premature withdrawal from the neoadjuvant treatment with PH FDC SC and P+H IV 9. Incidence of premature withdrawal from the adjuvant treatment with PH FDC SC 10. Incidence of premature withdrawal from the treatment with trastuzumab emtansine IV 11. Targeted vital signs and Physical findings 12. Targeted clinical laboratory test results |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. HCPQs Neoadjuvant phase: Day 1 of Cycle 1 up to 5 or 7 (depends on chosen neo scheme) for question 1; Day 1 of the last cycle (6 or 8) for the rest 2. Post-surgery 3. Day 1 of Cycle 1 and last cycle (6 or 8, depends on chosen neoadjuvant scheme) 4. Those with pCR: Day 1 of Cycle 1, 3, 5, 8 and last cycle 5. HCPQs Adjuvant phase: Day 1 of Cycle 5 and 8 for question 1; Day 1 of Cycle 8 for the rest 6. Those without pCR (Arm E): Day 1 of Cycle 1, 7 and 14 7. Up to 6 to 9 months after the last dose in the adjuvant phase 8. Cycle 1 to Cycle 6 or 8 (depends on chosen neoadjuvant scheme) 9. From Cycle 1 until the last cycle (Cycle 12 or 14 according to the chosen neoadjuvant scheme) 10. From Cycle 1 to until the last cycle (Cycle 14) 11-12. Throughout the study up to 18 months |
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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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Patient preference to home administration, Quality of life (QoL), time/resource use and convenience |
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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 | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
BRAZOS DE TRATAMIENTO MÚLTIPLE |
MULTIPLE TREATMENT ARMS |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 |
Bosnia and Herzegovina |
Brazil |
Canada |
Chile |
Costa Rica |
India |
Kenya |
Korea, Republic of |
Mexico |
Peru |
Russian Federation |
Singapore |
South Africa |
Turkey |
Croatia |
Czechia |
Bulgaria |
Spain |
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E.8.7 | Trial has a data monitoring committee | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |