E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed/Refractory Triple-Negative Breast Cancer |
Cáncer de mama triple negativo metastásico resistente o recidivante |
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E.1.1.1 | Medical condition in easily understood language |
Triple-Negative breast cancer who has progressed or returned |
Cáncer de mama triple negativo que ha progresado o regresado |
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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 | PT |
E.1.2 | Classification code | 10075566 |
E.1.2 | Term | Triple negative 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 | 20.0 |
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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10055113 |
E.1.2 | Term | Breast cancer metastatic |
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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006198 |
E.1.2 | Term | Breast cancer recurrent |
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 |
The primary objective of this study is to compare the efficacy of sacituzumab govitecan to the treatment of physician’s choice (TPC) as measured by progression-free survival (PFS) in patients with metastatic TNBC previously treated with at least two systemic chemotherapy regimens. |
El objetivo principal de este estudio es comparar la eficacia de sacituzumab govitecan con el tratamiento elegido por el médico (TEM) determinada por la supervivencia libre de progresión (SLP) en pacientes con CMTN metastásico tratados previamente con al menos dos pautas quimioterapéuticas sistémicas. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to compare between the two treatment groups for: - Overall Survival (OS) - Independently-determined Objective Response Rate (ORR), duration of response and time to onset of response per RECIST 1.1 criteria - Quality of life - Safety (adverse events, safety laboratories, incidence of dose delays and dose reductions, treatment discontinuations due to adverse events) |
Los objetivos secundarios del estudio son comparar entre los dos grupos de tratamiento: - La supervivencia global (SG) - La tasa de respuesta objetiva (TRO) determinada independientemente, la duración de la respuesta y el tiempo hasta el inicio de la respuesta según los criterios RECIST 1.1 - La calidad de vida - La seguridad (acontecimientos adversos, análisis de seguridad, incidencia de retrasos en la administración de la dosis y reducciones de la dosis, interrupciones del tratamiento debido a acontecimientos adversos) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Female or male patients, >18 years of age, able to understand and give written informed consent. • Histologically or cytologically confirmed TNBC per ASCO/CAP criteria, based on the most recent analyzed biopsy or other pathology specimen. • Metastatic disease documented by CT or MRI imaging. • Measurable disease by CT or MRI as per RECIST 1.1. Bone-only disease is not permitted. • Brain MRI must be done for patients with brain metastasis and patient must have had stable CNS disease for at least 4 weeks • At least 2 weeks beyond high dose systemic corticosteroids (however, low dose corticosteroids ≤ 20 mg prednisone or equivalent daily are permitted provided the dose is stable for 4 weeks). • Refractory to or relapsed after at least two prior standard of care chemotherapy regimens for unresectable, locally advanced or metastatic breast cancer. (These regimens will qualify regardless of triple-negative status at the time they were given. There is no upper limit in the number of prior chemotherapies and earlier adjuvant or neoadjuvant therapy for more limited disease will qualify as one of the required prior regimens if the development of unresectable, locally advanced or metastatic disease occurred within a 12-month period of time after completion of chemotherapy). • All patients must have been previously treated with a taxane regardless of disease stage (adjuvant, neoadjuvant or advanced) when it was given. • Eligible for one of the chemotherapy options listed as TPC (Eribulin, capecitabine, gemcitabine, or vinorelbine) as per investigator assessment. • ECOG performance score of 0 or 1. • Adequate hematology without ongoing transfusional support (hemoglobin > 9 g/dL, ANC > 1,500 per mm3, platelets > 100,000 per mm3). • Adequate renal and hepatic function (creatinine clearance of > 60 ml/min, may be calculated using Cockcroft-Gault equation; bilirubin ≤ 1.5 IULN, AST and ALT ≤ 3.0 x IULN or 5 x IULN if known liver metastases). • Recovered from all toxicities to Grade 1 or less by NCI CTCAE v4.00 (except alopecia or peripheral neuropathy that may be Grade 2 or less) at the time of randomization. Patients with Grade 2 neuropathy are eligible but may not receive vinorelbine as TPC. • Patients must have completed all prior cancer treatments at least 2 weeks prior to randomization including chemotherapy (includes also endrocrine treatment), radiotherapy and major surgery. Note: Prior antibody treatment for cancer must have been completed at least 3 weeks prior to randomization. • Prior investigational agents are permitted, provided completion according to the timeframes above. |
- Varones o mujeres, ≥ 18 años de edad, que puedan entender y otorgar el consentimiento informado por escrito. - CMTN confirmado histológica o citológicamente conforme a los criterios ASCO/CAP, en base a la biopsia más reciente analizada u otra muestra patológica. - Enfermedad metastásica verificada mediante TAC o RM. - Enfermedad mensurable mediante TAC o RM conforme a los criterios RECIST 1.1. No se permite la enfermedad exclusivamente ósea. - A los pacientes con metástasis cerebral se les debe realizar una RM del cerebro y los pacientes deben haber tenido enfermedad del SNC estable durante al menos 4 semanas. - Al menos 2 semanas después de recibir corticoesteroides sistémicos en dosis altas (sin embargo, se permiten corticoesteroides en dosis bajas de ≤ 20 mg de prednisona o equivalente diariamente siempre que la dosis permanezca estable durante 4 semanas). - Resistente o recidivante después de al menos dos pautas de quimioterapia de referencia previas para el cáncer de mama irresecable, localmente avanzado o metastásico (Anexo 1). (Estas pautas se tomarán en consideración con independencia del estado triple negativo en el momento en que fueron administradas. No hay un límite máximo en el número de quimioterapias previas, y el tratamiento adyuvante o neoadyuvante previo para la enfermedad más limitada se considerará como una de las pautas previas requeridas si la aparición de la enfermedad irresecable, localmente avanzada o metastásica se produjo en un periodo de 12 meses tras la finalización de la quimioterapia). - Todos los pacientes deben haber sido tratados previamente con un taxano con independencia de la fase de la enfermedad (adyuvante, neoadyuvante o avanzada) cuando se administró. - Aptos para una de las opciones de quimioterapia incluidas como TEM (eribulina, capecitabina, gemcitabina, o vinorelbina) según la evaluación del investigador. - Puntuación del estado funcional de 0 o 1según el ECOG (Anexo 2). - Una hematología adecuada sin el apoyo de transfusiones en curso (hemoglobina > 9 g/dl, RAN > 1500 por mm3, plaquetas > 100.000 por mm3). - Funciones renal y hepática adecuadas (aclaramiento de creatinina de > 60 ml/min, puede calcularse mediante la ecuación de Cockcroft-Gault; bilirrubina ≤ 1,5 LSNI, AST y ALT ≤ 3,0 x LSNI o 5 x LSNI si hay metástasis hepáticas conocidas). - Recuperados de todas las toxicidades a grado 1 o inferior según los CTCAA del NCI v4.00 (excepto alopecia o neuropatía periférica que pueden ser de grado 2 o inferior) en el momento de la aleatorización. Los pacientes con neuropatía de grado 2 son aptos pero no pueden recibir vinorelbina como TEM. - Los pacientes deben haber completado todos los tratamientos antineoplásicos previos al menos 2 semanas* antes de la aleatorización, incluida la quimioterapia (también incluye el tratamiento endocrino), radioterapia y cirugía mayor. *El tratamiento previo con anticuerpos contra el cáncer debe haberse completado al menos 3 semanas antes de la aleatorización. - Se permite el uso previo de fármacos experimentales, siempre que la finalización esté conforme con los plazos indicados anteriormente. |
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E.4 | Principal exclusion criteria |
• Women who are pregnant or lactating. • Women of childbearing potential or fertile men unwilling to use effective contraception during study until conclusion of 4-week post-treatment evaluation period. • Patients with Gilbert’s disease. • Presence of bulky disease (defined as any single mass > 7 cm in its greatest dimension). • Patients with non-melanoma skin cancer or carcinoma in situ of the cervix are eligible, while patients with other prior malignancies must have had at least a 3-year disease-free interval. • Patients known to be HIV positive, hepatitis B positive, or hepatitis C positive. • Known history of unstable angina, MI, or CHF present within 6 months of randomization or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring anti-arrhythmia therapy. • Known history of clinically significant active COPD, or other moderate-to-severe chronic respiratory illness present within 6 months of randomization. • Prior history of clinically significant bleeding, intestinal obstruction, or GI perforation within 6 months of randomization. • Infection requiring antibiotic use within one week of randomization. • Patients with a history of an anaphylactic reaction to irinotecan. • Other concurrent medical or psychiatric conditions that, in the Investigator’s opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations. |
- Mujeres que estén embarazadas o en período de lactancia. - Mujeres con capacidad para procrear o varones fértiles que no estén dispuestos a utilizar un método anticonceptivo eficaz durante el estudio hasta la conclusión del período de evaluación posterior al tratamiento de 4 semanas. - Pacientes con la enfermedad de Gilbert. - Presencia de neoplasia maligna con gran masa tumoral (definida como cualquier masa única > 7 cm en su dimensión máxima). - Los pacientes con cáncer de piel no melanómico o carcinoma in situ del cuello uterino son aptos, mientras que los pacientes con otras neoplasias malignas previas deben haber tenido al menos un intervalo sin enfermedad de 3 años. - Los pacientes que se sabe que son positivos para VIH, positivos para hepatitis B o positivos para hepatitis C. - Antecedentes conocidos de angina de pecho inestable, IM o ICC presente en los 6 meses previos a la aleatorización o arritmia cardíaca clínicamente significativa (distinta de fibrilación auricular estable) que requiera tratamiento antiarrítmico. - Antecedentes conocidos de EPOC activa clínicamente significativa u otra enfermedad respiratoria crónica moderada o grave en los 6 meses previos a la aleatorización. - Antecedentes previos de hemorragia clínicamente significativa, obstrucción intestinal o perforación digestiva en los 6 meses previos a la aleatorización. - Infección que requiera el uso de antibióticos en el plazo de una semana antes de la aleatorización. - Pacientes con antecedentes de una reacción anafiláctica a irinotecán. - Otras enfermedades o trastornos psiquiátricos concurrentes que, en opinión del investigador, es probable que puedan confundir la interpretación del estudio o impedir la realización de los procedimientos del estudio y los exámenes de seguimiento. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) as determined by an independent centralized blinded assessment. |
Supervivencia libre de progresión (SLP) según lo determinado por una evaluación enmascarada centralizada e independiente. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Monitored throughout the study |
Monitorizada a lo largo del estudio |
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E.5.2 | Secondary end point(s) |
- Overall survival (OS) - Objective response rate (ORR), duration of response, and time to onset of response - Quality of life - Safety, including: adverse events; safety laboratories and evaluations; incidence of dose delays and dose reductions; and treatment discontinuations due to adverse events |
- La supervivencia global (SG) - La tasa de respuesta objetiva (TRO), la duración de la respuesta y el tiempo hasta el inicio de la respuesta - La calidad de vida - La seguridad, incluidos: acontecimientos adversos, evaluaciones y análisis de seguridad, incidencia de retrasos en la administración de la dosis y reducciones de la dosis, e interrupciones del tratamiento a causa de los acontecimientos adversos |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Monitored throughout the study |
Monitorizada a lo largo del estudio |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | 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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 54 |
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 |
Canada |
France |
Germany |
Ireland |
Italy |
Spain |
United Kingdom |
United States |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 16 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 16 |