E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Breast Cancer |
Cáncer de mama |
|
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 | 19.0 |
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) |
|
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 select in the first part the SAR566658 dose based on Objective Response Rate (ORR) and safety of 2 dose levels and to demonstrate in the second part the efficacy of the selected dose based on ORR. |
En la primera parte, seleccionar la dosis de SAR566658 basada en la Tasa de Respuesta Objetiva (TRO) y la seguridad de 2 niveles de dosis de SAR566658 En la segunda parte, demostrar la eficacia de la dosis seleccionada en base a la TRO . |
|
E.2.2 | Secondary objectives of the trial |
- To assess: - Disease Control Rate (DCR), Duration Of Response (DOR), Progression-Free Survival (PFS), and Time To Progression (TTP) ; - The PK profile of SAR566658 - The impact of ocular primary prophylaxis on the incidence of keratopathies ; - The potential immunogenicity of SAR566658 ; - The relationship between CA6 expression level in the tumor, and circulating CA6 in blood at baseline, and efficacy outcomes
- To evaluate the global safety profile. |
- Evaluar: - La Tasa de Control de la Enfermedad (TCE), Duración de la Respuesta (DuR), Supervivencia Libre de Progresión (SLP) y Tiempo Transcurrido hasta la Progresión (TTP) - El perfil farmacocinético de SAR566658 - El impacto de la profilaxis primaria ocular sobre la incidencia de queratopatías; - El potencial inmunogenicidad de SAR566658; - La relación entre el nivel de expresión CA6 en el tumor, y CA6 circulante en de sangre al inicio del estudio, y los resultados de eficacia
- Para evaluar el perfil global de seguridad. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Measurable Metastatic triple negative breast cancer (TNBC). -Patients with CA6-positive disease. -Patients received at least 1 prior chemotherapy regimen but no more than 3 for advanced/metastatic disease. -Prior anticancer therapy must have contained anthracycline (eg, doxorubicin), if not contraindicated, and a taxane (eg, docetaxel, paclitaxel) in an adjuvant/neo-adjuvant or metastatic setting. |
- Cáncer de mama triple negativo metastásico y medible. - Pacientes con enfermedad con CA6 positivo - Pacientes que han recibido al menos 1 tratamiento previo con quimioterapia, pero no más de 3 para la enfermedad avanzada/metastásica. - El tratamiento antineoplásico previo debe haber contenido antraciclinas (p. ej., doxorrubicina), si no están contraindicadas, y un taxano (p. ej., docetaxel, paclitaxel) como tratamiento adyuvante/neoadyuvante o en pacientes con metástasis. - Consentimiento informado por escrito y firmado. |
|
E.4 | Principal exclusion criteria |
-Eastern Cooperative Oncology Group (ECOG) performance status ≥2. -Patient less than 18 years old. -Pregnant or breast-feeding women. -Patients with reproductive potential who do not agree to use accepted and effective method of contraception during the study treatment period and for 6 months following discontinuation of study drug. -Wash out period of less than 3 weeks or 5 half-lives from previous antitumor chemotherapy, immunotherapy, or any investigational treatment. -History of brain metastasis (other than totally resected or previously irradiated and nonprogressive/relapsed), spinal cord compression or carcinomatous meningitis, or new evidence of brain leptomeningeal disease. -Prior treatment with eribulin as last prior therapy or prior maytansinoid treatments (DM1 or DM4 antibody-drug conjugates [ADCs]). -Known intolerance to infused protein products including other monoclonal antibodies and ADCs. -Poor bone marrow reserve and/or poor organ function. -Symptomatic peripheral neuropathy Grade ≥2. -Previous history of chronic corneal diseases (even if asymptomatic) or unresolved acute nonrecurrent corneal conditions. -Patients wearing contact lenses who are not willing to stop wearing them for the duration of the study. -Medical conditions requiring concomitant administration of strong CYP3A4 inhibitors, unless it can be discontinued at least 2 weeks before 1st administration of SAR566658. -Contraindications to the use of ophthalmic vasoconstrictor and/or corticosteroid. |
- Estado funcional del ECOG superior o igual a 2. - Paciente menor de 18 años. - Mujeres embarazadas o en periodo de lactancia - Paciente con posibilidad de quedarse embarazada que no desee utilizar métodos anticonceptivos aceptados y eficaces durante el periodo de tratamiento del estudio y durante 6 meses tras la interrupción del fármaco del estudio. - Periodo de reposo farmacológico de menos de 3 semanas o de 5 vidas medias de tratamientos previos con quimioterapia antineoplásica, inmunoterapia o con cualquier tratamiento en investigación. - Antecedentes de metástasis cerebral (que no esté totalmente resecada o que no haya recibido radioterapia y que no sea progresiva/recidivante), compresión de la médula espinal o meningitis carcinomatosa o nuevos indicios de enfermedad leptomeníngea cerebral. - Tratamiento anterior con eribulina como última terapia previa o tratamientos anteriores con maitansinoides - Intolerancia conocida a la infusión de productos proteínicos, incluidos otros anticuerpos monoclonales y CAF. - Reserva deficiente en la médula ósea y/o Función orgánica deficiente - Neuropatía periférica sintomática de Grado superior o igual a 2 - Antecedentes de enfermedades de la córnea crónicas (incluso si permanecen asintomáticas) o enfermedades de la córnea no recurrentes agudas sin resolver. - Pacientes que utilicen lentes de contacto y que no quieran dejar de usarlas durante el estudio. - Enfermedades que requieran la administración concomitante de un inhibidor potente del CYP3A4 (véase el Apéndice F), a menos que pueda interrumpirse al menos 2 semanas antes de la primera administración de SAR566658. - Uso contraindicado de vasoconstrictores oftalmológicos y/o corticosteroides |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Objective response rate |
Tasa de Respuesta Objetiva (TRO) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
evaluation at 18 months |
Evaluación a los 18 meses |
|
E.5.2 | Secondary end point(s) |
1/ Disease control rate 2/ Duration of response - time 3/ Progression free survival - time 4/ Time to progression 5/ Number of keratopathies 6/ Incidence of positive patients for antidrug antibodies as a measure of SAR566658 immunogenicity |
1 / Tasa de Control de la Enfermedad 2 / Duración de la respuesta - tiempo 3 / Supervivencia libre de progresión - tiempo 4 / El tiempo de progresión 5 / Número de queratopatías 6 / Incidencia de pacientes positivos para anticuerpos contra el medicamento como una medida de la inmunogenicidad SAR566658 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-2 : at 18 months 3-4 : at 2 years 5 : Up to 30 days after the 3-week treatment cycle(s) (until 30 days after last treatment administration) 6 : Up to 60 days after the 3-week treatment cycle(s) (until 60 days after last treatment administration) |
1-2: a los 18 meses 3-4: a los 2 años 5: hasta 30 días después del ciclo de tratamiento de 3 semanas (s) (hasta 30 días después de la última administración del tratamiento) 6: hasta 60 días después del ciclo de tratamiento de 3 semanas (s) (hasta 60 días después de la última administración del tratamiento) |
|
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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | No |
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 | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
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 | 23 |
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 |
Czech Republic |
France |
Italy |
Netherlands |
Spain |
United States |
|
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
|
LVLS |
Última visita del último paciente |
|
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 | 4 |
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 | 4 |