| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| advanced (FIGO stage III-IV), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer (who responded to front-line platinum-based chemotherapy) |
| Cáncer epitelial de ovario avanzado (estadio FIGO III-IV), peritoneal primario o de las trompas de Falopio de alto grado, recientemente diagnosticado ( que han respondido al tratamiento en primera línea con quimioterapia a base de platino) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Ovarian Cancer Patients (who responded to previous platinum-based chemotherapy) |
| Pacientes con cancer de ovario ( que han respondido previamente a quimioterapia a base de platino |
|
| 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 | PT |
| E.1.2 | Classification code | 10016180 |
| E.1.2 | Term | Fallopian tube cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061328 |
| E.1.2 | Term | Ovarian epithelial cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061269 |
| E.1.2 | Term | Malignant peritoneal neoplasm |
| 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 | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To evaluate PFS by Response Evaluation Criteria in Solid Tumors (RECIST), as assessed by the investigator, in molecularly-defined HRD subgroups, using the following parallel comparisons:
- Arm A (oral rucaparib+ intravenous [IV] nivolumab) versus Arm B (oral rucaparib+IV placebo)
- Arm A (oral rucaparib+IV nivolumab) versus Arm D (placebo [oral and IV])
- Arm B (oral rucaparib+IV placebo) versus Arm D (placebo [oral and IV]) |
Evaluar la SLP mediante los Criterios de evaluación de la respuesta en tumores sólidos (Response Evaluation Criteria in Solid Tumors, RECIST), tal como evalúe el investigador, en subgrupos con DRH definida molecularmente, usando las siguientes comparaciones paralelas:
-Grupo A (rucaparib oral + nivolumab intravenoso [i.v.]) frente al grupo B (rucaparib oral + placebo i.v.)
-Grupo A (rucaparib oral + nivolumab i.v.) frente al grupo D (placebo [oral e i.v.])
-Grupo B (rucaparib oral + placebo i.v.) frente al grupo D (placebo [oral e i.v.]) |
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate PFS by RECIST, as assessed by the blinded independent central review (BICR), in molecularly-defined HRD subgroups
• To evaluate survival benefit
• To evaluate the objective response rate (ORR) and duration of response (DOR), as assessed by the investigator, in patients with measurable disease at baseline
• To evaluate safety |
•Evaluar la SLP mediante los criterios RECIST, determinada mediante una revisión central independiente enmascarada (RCIE) en subgrupos con DRH definida molecularmente.
•Evaluar el beneficio en la supervivencia.
•Evaluar la tasa de respuesta objetiva (TRO) y la duración de la respuesta (DdR), tal como evalúe el investigador, en pacientes con enfermedad mensurable al inicio.
•Evaluar la seguridad. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Newly diagnosed advanced (FIGO stage III-IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer
• Completed cytoreductive surgery, including at least a bilateral salpingo-oophorectomy and partial omentectomy, either prior to chemotherapy (primary surgery) or following neoadjuvant chemotherapy (interval debulking)
• Completed first-line platinum-based chemotherapy and surgery with a response, in the opinion of the Investigator
• Sufficient tumor tissue for planned analysis
• ECOG performance status of 0 or 1 |
* Reciente diagnóstico de cáncer peritoneal primario, de trompas de Falopio o epitelial de ovario de alto grado, avanzado (FIGO en fase III-IV)
* Cirugía citorreductora finalizada, incluyendo al menos una salpingo-ovariectomía bilateral y omentectomía parcial, ya sea antes de la quimioterapia (cirugía primaria) o después de la quimioterapia neoadyuvante (citorreducción en intervalos)
* Primera línea de quimioterapia basada en platino completada y cirugía con respuesta, en opinion del investigador
* tejido tumoral suficiente para los análisis planeados
* Estado funcional (ECOG) de 0 o 1 |
|
| E.4 | Principal exclusion criteria |
• Pure sarcomas or borderline tumors or mucinous tumors
• Active second malignancy
• Known central nervous system brain metastases
• Any prior treatment for ovarian cancer, other than the first-line platinum regimen
• Evidence of interstitial lung disease, active pneumonitis, myocarditis or a history of myocarditis
• Active, known or suspected autoimmune disease (e.g. autoimmune hepatitis)
• Condition requiring active systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications |
* Sarcomas puros o tumors con resultado limítrofe o tumors mucinosos
* Neoplasia maligna secundaria
* Metástasis cerebrales conocidas en el sistema nervioso central
* Cualquier tratamiento previo para el cancer de ovario diferente del tratamiento de primera línea con platino
* Evidencia de enfermedad pulmonary intersticial , neumonitis activa, miocarditis o historia de miocarditis
* Activa, conocida o sospecha de enfermedad autoimmune ( ej. hepatitis autoimmune)
* Condiciones que requieran tratamiento sistémico active con corticoids (>10 mg diarios de equivalente a prednisona) u otros medicamentos inmunosupresores |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint for the study is investigator-determined progression-free survival (PFS) by RECIST v1.1. Investigator-determined PFS is defined as the time from randomization to disease progression, according to RECIST v1.1 criteria as assessed by the investigator, or death due to any cause, whichever occurs first. |
| El criterio de valoración principal de eficacia del estudio es la SLP determinada por el investigador (SLPinv) según los criterios RECIST v1.1. La SLP determinada por el investigador se define como el momento desde la aleatorización hasta progresión de la enfermedad, conforme a los criterios RECIST v1.1, evaluada por el investigador, o fallecimiento por cualquier causa, lo que ocurra primero. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Tumor assessment measurements will be performed at screening, at the end of every 12 weeks of treatment (up to 7 days prior permitted) relative to Cycle 2 Day 1 for the first 3 years after initiation of oral/ IV study treatment and then every 24 weeks thereafter until objective radiological disease progression, at discontinuation of treatment, and as clinically indicated. |
| Las medidas de tumor serán llevadas a cabo en la selección, al final de cada 12 semanas de tratamiento ( hasta 7 días antes permitido) relative a ciclo2día1 para los 3 primeros años tras la inicición vía oral/IV del tratamiento del studio y entonces cada 24 semanas hasta progression de la enfermedad radiológicamente , discontinuación del tratamiento, y cuando esté indicado clinicamente |
|
| E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoints:
Progression-free survival (PFS) as assessed by blinded independent central review (BICR) by RECIST is defined as the time from randomization to disease progression, according to RECIST v1.1 criteria as assessed by BICR, or death due to any cause, whichever occurs first. Only tumor scans prior to start of any subsequent anti-cancer treatment are included.
Overall survival is defined as the time from randomization to death due to any cause.
Analyses of objective response rate (ORR) will be performed in the subgroup of patients with measurable disease at baseline and will be summarized with frequencies and percentages. Duration of response is defined as the interval from the first documentation of objective response (RECIST v1.1) to the earlier of the first documentation of disease progression (per RECIST v1.1) or death from any cause.
Safety Analysis:
Adverse events, clinical laboratory results, vital signs, ECOG performance status, body weight, and concomitant medications/procedures |
Criterios de valoración secundarios de eficacia:
La SLP determinada por la revisión del RCIE (SLPrcie) según los criterios RECIST se define como el momento desde la aleatorización hasta progresión de la enfermedad, conforme a los criterios RECIST v1.1, evaluada por el RCIE, o fallecimiento por cualquier causa, lo que ocurra primero. Solamente se incluyen los estudios de imágenes tumorales antes del inicio de cualquier tratamiento antineoplásico posterior.
La supervivencia global se define como el período desde la aleatorización hasta el fallecimiento por cualquier causa.
Los análisis de la TRO se realizarán en el subgrupo de pacientes con enfermedad mensurable al inicio y se resumirán con frecuencias y porcentajes. La duración de la respuesta se define como el intervalo desde la primera documentación de respuesta objetiva (criterios RECIST v1.1) hasta la primera documentación de progresión de la enfermedad (según criterios RECIST v1.1) o fallecimiento por cualquier causa.
Análisis de seguridad
Efectos adversos, resultados clínicos de laboratorio, signos vitals, estado ECOG, peso corporal, y medicación concomitante/procedimientos |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy: as for primary endpoint; (Overall survival is monitored continuously)
Safety: at every study visit |
Eficacia: como la variable principal; ( se monitoriza la supervivencia global continuadamente)
Seguridad: en cada visita del estudio |
|
| 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 | 4 |
| 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 | 11 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 100 |
| 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 |
| Belgium |
| Canada |
| Denmark |
| Finland |
| Germany |
| Greece |
| Ireland |
| Israel |
| Italy |
| Japan |
| New Zealand |
| Poland |
| Romania |
| Russian Federation |
| Spain |
| Sweden |
| Turkey |
| Ukraine |
| United Kingdom |
| United States |
|
| 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
|
| LVLS |
| Última visita del ultimo paciente |
|
| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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