E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hormone receptor (HR)-positive/HER2-negative locally advanced unresectable or metastatic breast cancer |
CÁNCER DE MAMA POSITIVO PARA RECEPTORES HORMONALES Y NEGATIVO PARA HER2 LOCALMENTE AVANZADO O METASTÁSICO |
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E.1.1.1 | Medical condition in easily understood language |
HRs are found inside breast cells, HER2 is found on surface of breast cells. Cancers with detectable HR that do not have high levels of HER2 gene/HER2 protein are called HR-positive; HER2-negative |
Los RH se encuentran dentro de las cél mam, HER2 se encuentra en la superficie de las células mam. Los cánceres con HR detec q no tienen niveles altos de gen HER2/prot HER2 se llaman HR-positHER2 neg |
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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 | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic breast cancer |
E.1.2 | System Organ Class | 100000004864 |
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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 | 10072740 |
E.1.2 | Term | Locally advanced breast cancer |
E.1.2 | System Organ Class | 100000004864 |
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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 |
To evaluate the efficacy of ipatasertib + palbociclib + fulvestrant compared with placebo + palbociclib + fulvestrant in the intent to treat (ITT) population and in patients with PIK3CA/AKT1/PTEN altered tumors (Phase III) |
Evaluar la eficacia de ipatasertib + palbociclib + fulvestrant en comparación con placebo + palbociclib + fulvestrant por intención de tratar la población de ITT y en pacientes con presencia de alteraciones PIK3CA / AKT1 / PTEN (Fase III) |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate additional efficacy of ipatasertib + palbociclib + fulvestrant compared with placebo + palbociclib + fulvestrant in the ITT population and in patients with PIK3CA/AKT1/PTEN altered tumors (Phase III) 2. To characterize the safety of combining ipatasertib with palbociclib + fulvestrant (Phase Ib and III) 3. To characterize the Pharmacokinetic profiles of ipatasertib and its metabolite (G-037720) in combination with palbociclib and fulvestrant (Phase Ib and III) |
1.Los HR se encuentran dentro de las células mamarias, HER2 se encuentra en la superficie de las células mamarias. Los cánceres con HR detectable que no tienen niveles altos de gen HER2 / proteína HER2 se llaman HR-positivos; HER2 negativo 2.Definir la seguridad de la combinación de ipatasertib con palbociclib +fulvestrant (Fase Ib y III) 3.Definir los perfiles FC de ipatasertib y su metabolito (G-037720) en combinación con palbociclib y fulvestrant (Fase Ib y III) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age >= 18 years - HR+ HER2- adenocarcinoma of the breast that is locally advanced unresectable or metastatic - For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs - For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm - Radiologic/objective relapse during adjuvant endocrine therapy or disease progression during the initial 12 months of 1L endocrine therapy in locally advanced unresectable or metastatic breast cancer - At least one measurable lesion via Response Evaluation Criteria in Solid Tumors, Version 1.1 - Phase III only: Tumor specimen from the most recently collected, available tumor tissue |
-Tener >_18 años -Presentar adenocarcinoma de mama HR+, HER2-,documentado histológicamente, localmente avanzado o metastásico -Las mujeres potencialmente fértiles deben comprometerse a practicar la abstinencia sexual o a usar métodos anticonceptivos, así como a no donar óvulos -Los varones deben comprometerse a practicar la abstinencia sexual o a usar preservativos, así como a no donar semen -Los pacientes deben haber presentado evidencia radiológica/objetiva de recidiva durante los 12 primeros meses de terapia endocrina en primera línea (1L),en el contexto del cáncer de mama localmente avanzado o metastásico inoperable -Presentar al menos una lesión medible, de acuerdo con los criterios RECIST v1.1 -Solo parte de fase III aleatorizada: muestra de tumor del tejido tumoral disponible |
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E.4 | Principal exclusion criteria |
- Pregnant or breastfeeding, or intending to become pregnant - Prior treatment with fulvestrant or other selective estrogen receptor down-regulator - Prior treatment with PI3K inhibitor, mTOR inhibitor or AKT inhibitor - Phase Ib only: Prior treatment with CDK4/6 inhibitor - Prior treatment with a cytotoxic chemotherapy regimen for metastatic breast cancer - History of Type I or Type II diabetes mellitus requiring insulin - History of or active inflammatory bowel disease or active bowel inflammation - Lung disease: pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections |
-Mujeres embarazadas, o que tengan intención de quedarse embarazadas -Tratamiento previo con fulvestrant u otros SERD, independientemente del contexto en el que se haya administrado -Tratamiento previo con un inhibidor de CDK4/6,mTOR,o AKT -Solo pacientes de la fase Ib: Tratamiento previo con un inhibidor de CDK4/6 - Tratamiento previo con un régimen de quimioterapia citotóxica para cáncer de mama metastásico -Antecedentes de diabetes mellitus de tipo I o II que requiera insulina -Antecedentes o presencia de enfermedades inflamatorias intestinales -Enfermedades pulmonares: neumonitis, enfermedad pulmonar intersticial, fibrosis pulmonar idiopática, fibrosis quística, aspergilosis, tuberculosis activa o antecedentes de infecciones oportunistas |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Progression-free survival (PFS) in ITT patients 2. PFS in patients with PIK3CA/AKT1/PTEN altered Tumors |
1. Supervivencia libre de progresión (SLP) en pacientes con ITT 2. PFS en pacientes con tumores alterados PIK3CA / AKT1 / PTEN |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase III 1-2. Up to 64 months |
Fase III 1-2. Hasta 64 meses |
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E.5.2 | Secondary end point(s) |
Phase III 1. Objective response rate (ORR) 2. Duration of objective response (DOR) 3. Clinical benefit rate (CBR) 4. Overall survival (OS) 5. Time to deterioration (TTD) in pain 6. TTD in physical functioning, role functioning, and Global Health Survey/Health-Related Quality of Life
Phase Ib and III 7. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 8. Change from baseline in targeted vital signs 9. Change from baseline in targeted clinical laboratory test results 10. Plasma concentration of ipatasertib and its metabolite, G-037720, at specified timepoints |
Fase III 1. Tasa de respuesta objetiva (ORR) 2. Duración de la respuesta objetiva (DOR) 3. Tasa de beneficio clínico (CBR) 4. Supervivencia global (OS) 5. Tiempo de deterioro (TTD) en el dolor. 6. TTD en funcionamiento físico, función de rol y Encuesta de salud global / Calidad de vida relacionada con la salud
Fase Ib y III 7. Incidencia y gravedad de los eventos adversos, y la gravedad se determina de acuerdo con los Criterios de Terminología Comunes para Eventos Adversos del National Cancer Institute, Versión 5.0 8. Cambio desde la línea de base en signos vitales específicos. 9. Cambio desde el inicio en los resultados de las pruebas de laboratorio clínico dirigidas. 10. Concentración de plasma de ipatasertib y su metabolito, G-037720, en puntos de tiempo especificados |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-9. Up to 64 months 10. Phase Ib: Cycle 1 Day 1 and 15; Cycle 2 and 3 Day 15; Phase III: Cycle 1 Day 1 and 15; Cycle 2 Day 15 |
1-9. Hasta 64 meses 10. Fase Ib: Ciclo 1 Día 1 y 15; Ciclo 2 y 3 Día 15; Fase III: Ciclo 1 Día 1 y 15; Ciclo 2 Día 15 |
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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 | 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 | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
with open-label phase Ib portion |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 |
Australia |
Brazil |
Canada |
Japan |
Korea, Republic of |
Spain |
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
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LPLV but the Sponsor may decide to terminate the study or OS follow-up at any time |
LPLV pero el Promotor puede decidir terminar el estudio o el seguimiento de la SG en cualquier momento |
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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 | 5 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial months | 4 |