E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic or Locally Advanced HER2-positive Breast Cancer |
Cáncer de mama HER2+ metastásico o localmente avanzado |
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E.1.1.1 | Medical condition in easily understood language |
Advanced Breast Cancer |
Cáncer de mama avanzado |
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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 | PT |
E.1.2 | Classification code | 10065430 |
E.1.2 | Term | HER-2 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 | 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 | 10072740 |
E.1.2 | Term | Locally advanced 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 |
The primary objective of this study is to evaluate the efficacy, as measured by progression-free survival (PFS) assessed by independent review and overall survival (OS), of margetuximab plus chemotherapy compared to trastuzumab plus chemotherapy in patients with advanced HER2+ breast cancer who have received prior treatment with trastuzumab, pertuzumab, and ado-trastuzumab emtansine in the neoadjuvant, adjuvant, or metastatic setting, and who have received at least one, and no more than two, lines of therapy in the metastatic setting. |
El objetivo principal del estudio es evaluar la eficacia, determinada mediante la supervivencia sin progresión (SSP) evaluada por revisores independientes, y la supervivencia global (SG) al administrar margetuximab más quimioterapia, en comparación con trastuzumab más quimioterapia, en pacientes con cáncer de mama HER2+ avanzado que hayan recibido tratamiento previo con trastuzumab, pertuzumab y ado-trastuzumab emtansina en un contexto de neoadyuvancia, adyuvancia o para la enfermedad metastásica, y que hayan recibido al menos una, y no más de dos, líneas de tratamiento para la enfermedad metastásica. |
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E.2.2 | Secondary objectives of the trial |
-To evaluate PFS, as assessed by study investigators, of margetuximab plus chemotherapy vs. trastuzumab plus chemotherapy in these patients. -To evaluate by independent review the objective response rate (ORR) of margetuximab plus chemotherapy vs. trastuzumab plus chemotherapy in these patients. |
-Evaluar, según la valoración de los investigadores del estudio, la SSP de estos pacientes al recibir margetuximab más quimioterapia frente a trastuzumab más quimioterapia. -Evaluar, según la valoración de los revisores independientes, la tasa de respuestas objetivas (TRO) de estos pacientes al recibir margetuximab más quimioterapia frente a trastuzumab más quimioterapia. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients >/= 18 years of age. 2. Have histologically-proven metastatic or locally-advanced relapsed/refractory HER2+ breast cancer. Tumors may be estrogen receptor (ER)/progesterone receptor (PR) positive or negative. 3. Have received prior treatment with pertuzumab, trastuzumab, and ado-trastuzumab emtansine in the neoadjuvant, adjuvant, or metastatic setting. Prior radiotherapy and hormonal therapies are allowed. 4. Have received treatment for at least one, and no more than two, lines of therapy in the metastatic setting. Prior neo-adjuvant or adjuvant therapy that resulted in relapse within 6 months of completion of therapy will be considered a line of treatment for metastatic disease. Eligible patients must have progressed on or following, the most recent line of therapy. 5. Resolution of all chemotherapy or radiation-related toxicities to </= Grade 1 (with exception of </= Grade 2 alopecia, stable sensory neuropathy, or stable electrolyte disturbances that are managed by supplementation). 6. Have life expectancy >/=12 weeks. 7. Have acceptable laboratory parameters. 8. Female patients of childbearing potential must have negative pregnancy test. All subjects should practice effective contraception. |
1. Edad >/= 18 años de edad. Los pacientes podrán ser varones o mujeres. 2. Padecer un cáncer de mama HER2+ metastásico o localmente avanzado, recidivante/refractario, demostrado histológicamente. Los tumores podrán ser positivos o negativos respecto al receptor de estrógenos (RE)/receptor de progesterona (RP). 3. Haber recibido tratamiento previo con pertuzumab, trastuzumab y ado-trastuzumab emtansina en un contexto de neoadyuvancia, adyuvancia o para la enfermedad metastásica. Se permitirá la radioterapia y la terapia hormonal previas. 4. Haber recibido tratamiento con al menos una, y no más de dos, líneas de tratamiento para la enfermedad metastásica. Si el resultado de un tratamiento neoadyuvante o adyuvante ha sido una recidiva dentro de los 6 meses siguientes a su finalización, dicho tratamiento se considerará una línea de tratamiento para la enfermedad metastásica. Los pacientes elegibles deberán haber progresado durante o después de la línea de tratamiento más reciente. 5. Resolución de todas las toxicidades de la quimioterapia o radioterapia hasta el Grado </=1 (con la excepción de la alopecia de Grado </=2, la neuropatía sensitiva estable o alteraciones electrolíticas estables que se puedan controlar con suplementos). 6. Esperanza de vida >/= 12 semanas. 7. Presentar los valores analíticos aceptables. 8. Las mujeres potencialmente fértiles deben presentar un resultado negativo de una prueba de embarazo. Todos los pacientes participantes en el estudio usarán un método anticonceptivo eficaz. |
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E.4 | Principal exclusion criteria |
1. Patients with known, untreated brain metastasis. Patients with signs or symptoms of brain metastasis must have a CT or MRI performed within 4 weeks prior to randomization to specifically exclude the presence of radiographically-detectable brain metastases. 2. History of uncontrolled seizures. 3. History of prior allogeneic bone marrow, stem-cell, or solid organ transplantation. 4. History of clinically significant cardiovascular disease 5. Clinically-significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation. 6. Any condition that would be a contraindication to receiving trastuzumab as described in the approved local label or a condition that would prevent treatment with the physician´s choice of chemotherapies. |
1.Pacientes con metástasis cerebrales conocidas y no tratadas. A los pacientes que presenten signos o síntomas de metástasis cerebrales se les practicará un TAC o una RMN dentro de las 4 semanas anteriores a la aleatorización para excluir, específicamente, la presencia de metástasis cerebrales radiológicamente detectables. 2.Antecedentes de convulsiones no controladas. 3.Antecedentes de trasplante alogénico de médula ósea, de células madre o de órganos sólidos. 4.Antecedentes de enfermedad cardiovascular clínicamente relevante 5.Riesgo pulmonar clínicamente relevante, incluida la necesidad de suplemento de oxígeno para mantener una oxigenación adecuada. 6.Toda patología que suponga una contraindicación para recibir trastuzumab según la ficha técnica local o que pueda impedir el tratamiento quimioterápico que el médico haya elegido. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival as determined by independent radiological review. Overall survival defined as the number of days from randomization to the date of death (from any cause). |
Supervivencia sin progresión determinada por una revisión radiológica independiente. Supervivencia global se define como el número de días desde la aleatorización hasta la fecha del éxitus (por cualquier causa) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
For PFS: 24 months from the start of the study For OS: 36 months from the start of the study |
Para SSP: 24 meses desde el inicio del estudio Para SG: 36 meses desde el inicio del estudio |
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E.5.2 | Secondary end point(s) |
Overall response rate (ORR) as determined by independent radiological review PFS as determined by study investigators |
Tasa de respuestas objetivas (TRO) determindad por revisión radiológica independiente SSP determinda por los investigadores del estudio |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For ORR: 36 months from the start of the study. For PFS: 24 months from the start of the study |
Para TRO: 36 meses desde el inicio del estudio Para SSP: 24 meses desde el inicio 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 | No |
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 | 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 | 18 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 115 |
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 |
Austria |
Belgium |
Canada |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Israel |
Italy |
Netherlands |
Portugal |
Spain |
Switzerland |
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
|
The end of this study is defined as when the last patient visit occurs or one year after the final survival analysis, whichever occurs first. |
El final de este estudio se define como el momento en que haya tenido lugar la última visita del último paciente, o bien cuando haya transcurrido 1 año después del análisis final de supervivencia, lo que ocurra en primer lugar. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |