| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Early stage triple negative breast cancer. |
| PACIENTES CON CÁNCER DE MAMA TRIPLE?NEGATIVO EN ESTADIO INICIAL |
|
| E.1.1.1 | Medical condition in easily understood language |
| Early stage breast cancer that tests negative for estrogen receptors, progesterone receptors and HER2 receptors. |
| PACIENTES CON CÁNCER DE MAMA EN ESTADIO INICIAL NEGATIVOS A RECEPTORES DE ESTRÓGENOS, PROGESTERONA Y HER2. |
|
| 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 | 17.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10057654 |
| E.1.2 | Term | Breast cancer female |
| 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 estimate the efficacy of ipatasertib combined with paclitaxel compared with placebo combined with paclitaxel in patients with early stage TNBC, as measured by evaluation of pCR rate within the breast and axilla (ypT0/Tis ypN0) in all patients and in patients with PTEN low tumors. |
| - Evaluar la eficacia de ipatasertib combinado con paclitaxel en comparación con placebo combinado con paclitaxel en pacientes con CMTN en estadio inicial, según lo determinado por la evaluación en el laboratorio local de anatomía patológica de la tasa de RCap en la mama y la axila (ypT0/Tis ypN0) en todas las pacientes y en las pacientes con tumores con PTEN bajo |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate objective response rate (ORR) assessed by breast MRI via modified Response Evaluation Criteria in Solid Tumors (RECIST) of ipatasertib combined with paclitaxel compared with placebo combined with paclitaxel in all patients and in patients with PTEN low tumors;
- To estimate the clinical activity, as measured by pCR (ypT0/Tis and ypT0/Tis ypN0) and ORR of ipatasertib combined with paclitaxel compared with placebo combined with paclitaxel in patients who are Akt diagnostic positive;
- To assess pCR rates according to subtypes of breast cancer defined by molecular profiles;
- To assess the rates of breast-conserving surgery (BCS) and conversion to BCS of ipatasertib combined with paclitaxel compared with placebo combined with paclitaxel in women with T2 or T3 tumors. |
-Determinar la tasa de respuestas objetivas (TRO), evaluada mediante RM de la mama aplicando los Criterios de evaluación de la respuesta en tumores sólidos (RECIST), de ipatasertib combinado con paclitaxel en comparación con placebo combinado con paclitaxel en todas las pacientes y en las pacientes con tumores con PTEN bajo
- Calcular la actividad clínica, medida mediante RCap (ypT0/Tis e ypT0/Tis ypN0), y la TRO de ipatasertib combinado con paclitaxel en comparación con placebo combinado con paclitaxel en pacientes con diagnóstico positivo de Akt (Dx+).
- Determinar las tasas de RCap en subtipos de cáncer de mama definidos por perfiles moleculares
- Calcular las tasas de CCM y conversión a CCM de ipatasertib combinado con paclitaxel en comparación con placebo combinado con paclitaxel en mujeres con tumores T2 o T3 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
? Premenopausal or postmenopausal women, age >18 years
? Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
? Histologically documented triple-negative carcinoma of the breast with all of the following characteristics:
- Primary tumor > or eqaul to 1.5 cm in largest diameter (cT1-3) by MRI. In the case of a multifocal tumor (defined as the presence of two or more foci of cancer within the same breast quadrant), the largest lesion must be > or equal to 1.5 cm and designated as the ?index? lesion for all subsequent tumor evaluations.
- Stage I to operable Stage IIIa breast cancer
? Adequate hematologic and organ function within 14 days before the first study treatment, defined by the following:
- Neutrophils (absolute neutrophil count [ANC] > or equal to 1500/microL)
- Hemoglobin > or equal to 9 g/dL
- Platelet count > or equal 100,000/microL
- Fasting serum glucose < or equal to 150 mg/dL (8.33 mmol/L) and HbA1C < or equal to 8%
? For women who are not postmenopausal (> or equal to 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 6 months after the last dose of study drug. |
-Mujeres premenopáusicas o posmenopáusicas, ? 18 años de edad
-Estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0 o 1
-Carcinoma de mama triple negativo confirmado por examen histológico con todas las características siguientes:
?Tumor primario ? 1,5 cm de diámetro máximo (cT1?3) mediante RM. En el caso de un tumor multifocal (definido como la presencia de dos o más focos de cáncer en el mismo cuadrante de la mama), la lesión más grande debe ser ? 1,5 cm y designarse como lesión ?de referencia? en todas las evaluaciones posteriores del tumor.
?Cáncer de mama en estadio I a estadio IIIa operable
-Función hematológica y orgánica adecuada en los 14 días previos al inicio del tratamiento del estudio, definida por los parámetros siguientes:
?Neutrófilos (recuento absoluto de neutrófilos [ANC] ?1500/µl)
?Hemoglobina ?9 g/dl
?Recuento de plaquetas ?100.000/µl
?Glucemia en ayunas ?150 mg/dl (8,33 mmol/l) y HbA1c ? 8 %.
?En las mujeres que no sean posmenopáusicas (? 12 meses de amenorrea no inducida por tratamiento) o quirúrgicamente estériles (ausencia de los ovarios o el útero): acuerdo para mantener la abstinencia o utilizar métodos anticonceptivos individuales o combinados que sumen una tasa de fallos < 1 % por año durante el período de tratamiento y durante al menos 6 meses después de la última dosis del fármaco del estudio |
|
| E.4 | Principal exclusion criteria |
? Any prior treatment for the current primary invasive breast cancer
? Patients with cT4 or cN3 stage breast tumors
? Metastatic (Stage IV) breast cancer
? Bilateral invasive breast cancer
? Multicentric breast cancer (the presence of more than one tumor in different quadrants of the breast)
? History of Type I or Type II diabetes mellitus requiring insulin
- Patients who are on a stable dose of oral diabetes medication > or equal to 2 weeks prior to initiation of study treatment are eligible for enrollment
? Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator?s opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications. |
-Cualquier tratamiento previo para el cáncer de mama primario invasivo actual
-Pacientes con tumores de mama en estadio cT4 o cN3
-Cáncer de mama metastásico (estadio IV)
-Cáncer de mama invasivo bilateral
-Cáncer de mama multicéntrico (presencia de más de un tumor en diferentes cuadrantes de la mama)
-Antecedentes de diabetes mellitus de tipo 1 o tipo 2 con necesidad de insulina
-Podrán participar pacientes que hayan estado recibiendo una dosis estable de antidiabéticos orales durante ? 2 semanas antes del comienzo del tratamiento del estudio
-Cualquier otra enfermedad, disfunción metabólica, hallazgo en la exploración física o resultado analítico que, en opinión del investigador, suscite sospechas razonables de una enfermedad o proceso que contraindique el uso de un fármaco en investigación o que pueda afectar a la interpretación de los resultados o suponer un riesgo elevado de complicaciones del tratamiento para la paciente. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The rate of pCR in breast and axilla (ypT0/Tis ypN0). The pCR endpoint will be analyzed for all randomized patients and for patients with PTEN low tumors. |
| ?Tasa de RCap en la mama y la axila definida por ypT0/Tis ypN0 .El criterio de valoración principal de la eficacia en todas las pacientes y en las pacientes con tumores con PTEN bajo es el siguiente: |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
? Tumor objective response rate (ORR) assessed by breast MRI via modified RECIST criteria, in all patients and in patients with PTEN-low tumors
? The rate of pCR and ORR in patients whose tumors are Akt Dx+ (defined by PTEN status, INPP4B status, and PI3K alterations)
? The rate of pCR according to subtypes of breast cancer defined by molecular profiles; e.g., PAM50 classifier
? The rate of breast-conserving surgery (BCS) and conversion to BCS in patients with T2 or T3 tumors |
? Respuesta objetiva del tumor mediante RM, evaluada por el investigador aplicando los RECIST modificados, en todas las pacientes y en las pacientes con tumores con PTEN bajo.
? Actividad clínica, medida mediante RCap y la TRO en pacientes con diagnóstico positivo de Akt Dx+ (definido por el estado de PTEN, el estado de INPP4B y las alteraciones de PI3K)
? Tasas de RCap en subtipos de cáncer de mama definidos por perfiles moleculares (p. ej., los subtipos intrínsecos de cáncer de mama definidos por PAM50)
? Tasas de CCM y conversión a CCM en mujeres con tumores T2 o T3 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Week 10, Week 19 |
| Semana 10, Semana 19 |
|
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| Tolerability |
| Tolerabilidad |
|
| 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 | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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) | No |
| E.8.2.2 | Placebo | Yes |
| 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 | 5 |
| 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 |
| Portugal |
| 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
|
|
| 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 | 3 |
| 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 | 3 |
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