E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent partially platinum sensitive or resistant epithelial ovarian, primary peritoneal, or fallopian tube cancer |
Cáncer epitelial de ovario, cáncer peritoneal primario o cáncer de las trompas de Falopio recurrentes y parcialmente sensibles o resistentes al platino |
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E.1.1.1 | Medical condition in easily understood language |
Fallopian Tube Cancer Ovarian Cancer Primary Peritoneal Cancer |
Cáncer de las trompas de Falopio Cáncer de ovario Cáncer peritoneal primario |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10066697 |
E.1.2 | Term | Ovarian 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 |
To determine if AMG 386 plus pegylated liposomal doxorubicin (PLD) is superior to placebo plus PLD as measured by progression-free survival (PFS). |
Determinar si AMG 386 más doxorubicina liposomal pegilada (DLP) es superior al placebo más DLP, cuantificado por la supervivencia libre de progresión (SLP). |
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E.2.2 | Secondary objectives of the trial |
To determine if AMG 386 plus PLD is superior to placebo plus PLD as measured by overall survival (OS). |
Determinar si AMG 386 más DLP es superior al placebo más DLP, cuantificado por la supervivencia global (SG). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
?Female of age 18 years or older ? Histologically or cytologically documented invasive epithelial ovarian, primary peritoneal, or fallopian tube cancer - Subjects with pseudomyxoma, mesothelioma, unknown primary tumor, sarcoma, carcinosarcoma, or neuroendocrine histology are excluded - Subjects with borderline ovarian cancer, ie, subjects with low malignant potential tumors, are excluded ? Radiographically documented disease progression either on or following the last dose of the prior regimen for epithelial ovarian, primary peritoneal, or fallopian tube cancer ? Radiographically evaluable disease per RECIST 1.1 with modifications - There must be radiographically visible tumor - Subjects with only ascites, pericardial, or pleural effusion are excluded ? Subjects must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound. This initial treatment may have included intraperitoneal therapy, high-dose therapy, consolidation therapy, neoadjuvant chemotherapy with interval surgery, bevacizumab or extended therapy administered after surgical or non-surgical assessment. - Subjects are allowed to have received, but are not required to have received, 2 additional cytotoxic regimens for management of recurrent or persistent disease ? ECOG performance status 0 or 1 ? Adequate hematological, renal and hepatic function ? Left ventricular ejection fraction (LVEF) ? institutional lower limit of normal ? Gerenrally well controlled blood pressure , defined as systolic blood pressure < 140 mmHg AND diastolic blood pressure < 90 mmHg |
? Mujer de 18 años o mayor. ? Cáncer epitelial de ovario, cáncer primario peritoneal o cáncer de las trompas de Falopio invasivos, documentados histológicamente o citológicamente. - Quedan excluidos los sujetos con pseudomixoma, mesotelioma, tumor primario desconocido, sarcoma, carcinosarcoma o histología neuroendocrina. - Quedan excluidos los sujetos con cáncer de ovario en el límite, es decir, los sujetos con tumores con bajo potencial maligno. ? Progresión de la enfermedad documentada radiológicamente coincidiendo con o después de la última dosis del régimen anterior para el cáncer epitelial de ovario, cáncer primario peritoneal o cáncer de las trompas de Falopio. ? Enfermedad evaluable radiológicamente según los RECIST 1.1 con modificaciones. - Debe existir un tumor radiológicamente visible. - Quedan excluidos los sujetos solo con ascitis o derrame pericárdico o pleural. ? Los sujetos deben haber recibido un régimen quimioterapéutico basado en platino para controlar la enfermedad primaria que incluya carboplatino, cisplatino u otro compuesto organoplatino. El tratamiento inicial puede haber incluido el tratamiento intraperitoneal, tratamiento a dosis altas, tratamiento de consolidación, quimioterapia neoadyuvante con cirugía de intervalo, bevacizumab o tratamiento extendido administrado tras la evaluación quirúrgica o no quirúrgica. - Los sujetos pueden haber recibido, aunque no es obligatorio, 2 regímenes citotóxicos adicionales para el tratamiento de la enfermedad recurrente o persistente. ? Estado funcional ECOG de 0 o 1 (véase el apéndice H). ? Funciones hematológica, renal y hepática adecuadas. ? Fracción de eyección del ventrículo izquierdo (FEVI) ? límite inferior de la normalidad institucional. ? Presión arterial bien controlada en general con PA sistólica ? 140 mmHg Y PA diastólica ? 90 mmHg antes de la aleatorización. |
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E.4 | Principal exclusion criteria |
? Subjects who have received more than 3 previous regimens of anti-cancer therapy for epithelial ovarian, primary peritoneal or fallopian tube cancer ? Subjects treated with pegylated liposomal doxorubicin (PLD) or any anthracycline-based or mitoxantrone-based chemotherapy ? Subjects with primary platinum-refractory disease - Subjects with recurrence or progression during the first 6 cycles or < 6 months after the beginning of the first-line platinum-based chemotherapy are excluded ? Subjects with platinum-free interval (PFI) > 12 months from their last platinum-based therapy ? History of arterial or venous thromboembolism within 12 months prior to randomization ? History of central nervous system metastasis ? Clinically significant cardiac disease within 12 months prior to randomization |
? Los sujetos que previamente hayan recibido más de tres regímenes de tratamiento contra el cáncer para el cáncer epitelial de ovario, cáncer primario peritoneal o cáncer de las trompas de Falopio. ? Los sujetos tratados con doxorubicina liposomal pegilada (DLP) o cualquier quimioterapia basada en antraciclina o mitoxantrona. ? Los sujetos con enfermedad primaria resistente al platino. - Quedan excluidos los sujetos con recurrencia o progresión durante los primeros 6 ciclos o < 6 meses tras el inicio de la quimioterapia basada en platino como tratamiento de primera línea. ? Los sujetos con un intervalo sin platino (ISP) > 12 meses desde el último tratamiento basado en platino. ? Antecedentes de tromboembolismo venoso o arterial en los 12 meses previos a la aleatorización. ? Antecedentes de metástasis en el sistema nervioso central. ? Enfermedad cardiovascular clínicamente significativa en los 12 meses previos a la aleatorización. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To determine if AMG 386 plus pegylated liposomal doxorubicin (PLD) is superior to placebo plus PLD as measured by progression-free survival (PFS), defined as the time from randomization to the earliest of the dates of first radiologic disease progression per RECIST 1.1 with modifications or death from any cause in subjects with recurrent partially platinum sensitive or resistant epithelial ovarian, primary peritoneal or fallopian tube cancer |
Determinar si AMG 386 más doxorubicina liposomal pegilada (DLP) es superior a placebo más DLP, cuantificado mediante la evaluación de la supervivencia libre de progresión (SLP), definida como el tiempo desde la fecha de aleatorización hasta la primera de las fechas de progresión radiológica de la enfermedad según los RECIST 1.1 con modificaciones o la muerte por cualquier causa en sujetos con cáncer epitelial de ovario, cáncer peritoneal primario o cáncer de las trompas de Falopio recurrentes y parcialmente sensibles o resistentes al platino. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
When a minimum of 293 PFS events have been observed |
Cuando se han observado un mínimo de 293 acontecimientos de SLP |
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E.5.2 | Secondary end point(s) |
? Objective response rate (ORR) ? Duration of response (DOR) ? CA-125 response rate per GCIG criteria ? Change in CA-125 ? Change in tumour burden ? Incidence of adverse events and significant laboratory abnormalities ? Pharmacokinetics of AMG 386 (eg, Cmax and Cmin) ? Incidence of anti-AMG 386 antibody formation ? Patient reported HRQOL and ovarian cancer related symptoms using FACT-O ? Overall health status using EQ-5D |
? Tasa de respuesta objetiva (TRO). ? Duración de la respuesta (DR). ? Tasa de respuesta del CA-125 según el GCIG. ? Cambio del CA-125. ? Cambio de la carga tumoral. ? Incidencia de acontecimientos adversos y anomalías analíticas significativas. ? Farmacocinética de AMG 386 (p. ej., Cmáx. y Cmín. ? Incidencia de formación de anticuerpos anti-AMG 386. ). ? Calidad de vida relacionada con la salud (HRQOL) notificada por los pacientes y síntomas relacionados con el cáncer de ovarios utilizando FACT-O. ? Estado general de salud utilizando EQ-5D. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
When a minimum of 295 OS events have been observed |
Cuando se han observado un mínimo de 295 acontecimientos de SG |
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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 | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 59 |
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 |
European Union |
Australia |
China |
Hong Kong |
Singapore |
Taiwan |
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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The end of study will occur 60 months after the last subject is randomized if all subjects have completed study treatment by that date. |
El fin del estudio tendrá lugar 60 meses después de la aleatorización del último sujeto si todos los sujetos han completado el tratamiento del estudio en esa fecha. |
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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 | 6 |
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 | 6 |
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 |