E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Newly diagnosed advanced (FIGO stage III-IV) high grade epithelial ovarian, fallopian or primary peritoneal cancer |
Cáncer avanzado recién diagnosticado (FIGO estadio III-IV) epitelial de ovario de alto grado, de falopio o peritoneal primario |
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E.1.1.1 | Medical condition in easily understood language |
Advanced ovarian, fallopian or primary peritoneal cancer |
ovario avanzado, de falopio o 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 | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10070907 |
E.1.2 | Term | Ovarian cancer stage III |
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 | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10070908 |
E.1.2 | Term | Ovarian cancer stage IV |
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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10016186 |
E.1.2 | Term | Fallopian tube cancer stage III |
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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10016187 |
E.1.2 | Term | Fallopian tube cancer stage IV |
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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052171 |
E.1.2 | Term | Peritoneal carcinoma |
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 the efficacy of durvalumab and olaparib assessed by PFS in the first line treatment of non-tBRCAm patients with newly diagnosed advanced ovarian cancer. |
Determinar la eficacia de durvalumab y olaparib evaluada mediante la SSP en el tratamiento de primera línea de pacientes sin tBRCAm con cáncer de ovario avanzado recién diagnosticado. |
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E.2.2 | Secondary objectives of the trial |
- OS in non-tBRCAm cohort - ORR, ORR pre-surgery in IDS group, duration of response, PFS2, TFST, TSST and TDT in non-tBRCAm cohort - Health-related Quality of Life Outcomes (HRQoL), global health status and ovarian cancer symptoms in non-tBRCAm cohort - pCR in patients undergoing IDS in non-tBRCAm cohort - PK and Ig of durvalumab in sampling of population - PK of olaparib in sampling of population -the potential additional clinical benefit in tBRCAm cohort (PFS, PFS2, ORR, ORR pre-surgery in IDS group, duration of response, TFST, TSST, TDT, HRQoL, proportion of patients with pCR in patients undergoing IDS) |
-SG en la cohorte sin tBRCAm -TRO, TRO antes de la intervención quirúrgica en el grupo de CCI, duración de la respuesta, SSP2, TFST, TSST y TDT en la cohorte sin tBRCAm -los efectos en la CVRS, el estado de salud general y los síntomas del cáncer de ovario en la cohorte sin tBRCAm -RCp en pacientes sometidas a CCI en la cohorte sin tBRCAm. -FC y la inmunogenicidad de durvalumab en muestra poblacional. -FC de olaparib en muestra poblacional. -posible beneficio clínico adicional en cohorte sin tBRCAm (SSP, SSP2, TRO, TRO antes de la intervención quirúrgica en el grupo de CCI, duración de la respuesta, TFST, TSST, TDT, QLQ-C30 de la EORTC y QLQ-OV28 de la EORTC, EQ5D-5L, Q-TWiST, QAPFS, proporción de pacientes con RCap en pacientes sometidas a CCI). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Female patients with newly diagnosed, histologically confirmed, advanced (Stage III-IV) high grade epithelial ovarian cancer including high grade serous, high grade endometriod, clear cell ovarian cancer or carcinosarcoma, primary peritoneal cancer and / or fallopian-tube cancer • Patients must be aged ≥18 years of age • All patients should be candidates for cytoreductive surgery either: upfront primary surgery OR plan to undergo chemotherapy with interval debulking surgery • Mandatory provision of tumour sample for centralised tBRCA testing • Evidence of presence or absence of BRCA1/2 mutation in tumour tissue • ECOG performance status 0-1 • Patients must have preserved organ and bone marrow function • Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test |
•Pacientes femeninas con cáncer ovárico epitelial de alto grado avanzado, histológicamente confirmado, avanzado (estadio III-IV) que incluye alto grado seroso, alto grado endometrial, cáncer de ovario de células claras o carcinosarcoma, cáncer peritoneal primario y / o cáncer de trompas de Falopio • Los pacientes deben ser mayores de 18 años. • Todos los pacientes deben ser candidatos para cirugía citorreductora: cirugía primaria inicial o planean someterse a quimioterapia con cirugía de reducción a intervalos • Provisión obligatoria de muestra de tumor para la prueba centralizada de tBRCA • Evidencia de presencia o ausencia de mutación BRCA1 / 2 en tejido tumoral • ECOG status 0-1 • Los pacientes deben tener preservada la función orgánica y de la médula ósea. • Posmenopáusicas o evidencia de estado no reproductivo para mujeres en edad fértil: prueba de embarazo en orina o suero negativa |
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E.4 | Principal exclusion criteria |
• Non-epithelial ovarian cancer, borderline tumors, low grade epithelial tumors or mucinous histology • Prior systemic anti-cancer therapy for ovarian cancer • Prior treatment with PARP inhibitor or immune mediated therapy • Planned intraperitoneal cytotoxic chemotherapy • Active or prior documented autoimmune or inflammatory disorders • Patients considered a poor medical risk due to a serious, uncontrolled intercurrent illness • Clinically significant cardiovascular disease • History of another primary malignancy except for - Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study treatment and of low potential risk for recurrence (patients who have received prior adjuvant chemotherapy for early stage breast cancer may be eligible, provided that it was completed ≥3 years prior to registration, and that the patient remains free of recurrent or metastatic disease) - Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease - Adequately treated carcinoma in situ without evidence of disease - Endometrial cancer FIGO Stage IA, Grade 1 or Grade 2 |
• Cáncer de ovario no epitelial, tumores límite, tumores epiteliales de bajo grado o histología mucinosa • Tratamiento sistémico previo contra el cáncer para el cáncer de ovario. • Tratamiento previo con inhibidor de PARP o terapia mediada por inmunidad. • Quimioterapia citotóxica intraperitoneal planificada • Trastornos autoinmunes o inflamatorios activos o previamente documentados. • Pacientes considerados de bajo riesgo médico debido a una enfermedad intercurrente grave e incontrolada. • Enfermedad cardiovascular clínicamente significativa. • Historia de otra neoplasia primaria a excepción de - Malignidad tratada con intención curativa y sin enfermedad activa ≥5 años antes de la primera dosis del tratamiento del estudio y con bajo riesgo potencial de recurrencia (los pacientes que han recibido quimioterapia adyuvante previa para el cáncer de mama en etapa temprana pueden ser elegibles, siempre que completado ≥3 años antes del registro, y que el paciente permanece libre de enfermedad recurrente o metastásica) - Cáncer de piel no melanoma o lentigo maligno tratados adecuadamente, sin evidencia de enfermedad - Carcinoma in situ tratado adecuadamente sin evidencia de enfermedad. - Cáncer de endometrio FIGO Etapa IA, Grado 1 o Grado 2 |
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E.5 End points |
E.5.1 | Primary end point(s) |
PFS is defined as the time from randomisation to the non-tBRCAm cohort until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from assigned therapy or receives another anticancer therapy prior to progression. |
La SSP se define como el tiempo desde la randomización hasta la cohorte sin tBRCAm hasta la fecha de progresión objetiva de la enfermedad o muerte (por cualquier causa en ausencia de progresión) independientemente de si el paciente se retira de la terapia asignada o recibe otra terapia contra el cáncer antes de la progresión |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Radiologic scans (assessed according to RECIST 1.1) performed from first patient enrolled to data cut off (approximately 40 months after first patient has received first dose of IP). |
Las exploraciones radiológicas (evaluadas de acuerdo con RECIST 1.1) realizadas desde el primer paciente inscrito hasta el corte de datos (aproximadamente 40 meses después de que el primer paciente haya recibido la primera dosis de IP). |
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E.5.2 | Secondary end point(s) |
Overall Survival (OS) Second Progression (PFS2) Objective Response Rate (ORR) Duration of response (DoR) Time to first subsequent therapy (TFST) Time to second subsequent therapy (TSST) Time to discontinuation or death (TDT) Pathological complete response (pCR) Health related Quality of Life (HRQoL) Pharmacokinetic and Immunogenicity |
Supervivencia global (SG) Segunda Progresión (SSP2) Tasa de respuesta objetiva (TRO) Duración de la respuesta (DR) Tiempo hasta el primer tratamiento posterior(TFST) Tiempo hasta el segundo tratamiento posterior (TSST) Tiempo hasta el abandono o la muerte; (TDT) Respuesta patológica completa (RpC) Calidad de vida relacionada con la salud (CVRS) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Radiologic scans performed from enrollment until first progression or death. For HRQoL, it will be assessed at multiple time points up to a maximum of 36 months or until the primary analysis, whichever comes first. For Durvalumab PK, measured at the end of first infusion of durvalumab, during and at the end of the chemotherapy phase, during the maintenance phase and after discontinuation of durvalumab. For Olaparib PK, concentrations will be measured on the third cycle of the maintenance phase. |
Las exploraciones radiológicas se realizaron desde el reclutamiento hasta la primera progresión o la muerte. Para la CVRS, se evaluará en múltiples puntos de tiempo hasta un máximo de 36 meses o hasta el análisis primario, lo que ocurra primero. Para Durvalumab PK, medido al final de la primera perfusión de durvalumab, durante y al final de la fase de quimioterapia, durante la fase de mantenimiento y después de la interrupción de durvalumab. Para Olaparib PK, las concentraciones se medirán en el tercer ciclo de la fase de mantenimiento |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
además de la cohorte doble ciega sin TBRCA, hay una cohorte tBRCAm de etiqueta abierta única |
in addition to double blinded non-tBRCA cohort, there is a single open label tBRCAm cohort |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 147 |
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 |
Bulgaria |
Canada |
China |
Denmark |
Finland |
France |
Germany |
Hungary |
Italy |
Japan |
Korea, Republic of |
Poland |
Spain |
Sweden |
Turkey |
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 is defined as the data cut-off point for the final analysis of OS in the non-tBRCAm cohort (at approximately 50% maturity or 5 years after the last non-tBRCAm patient is randomised to treatment, whichever occurs sooner). |
El final del estudio se define como el punto de corte de los datos para el análisis final de la SG en la cohorte sin tBRCAm (aproximadamente al 50% de la madurez o 5 años después de que el último paciente sin tBRCAm sea randomizado al tratamiento, lo que ocurra antes) . |
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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 | 4 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |