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 |
Tumore epiteliale ovarico avanzato (stadio FIGO III-IV) di alto grado, tumore delle tube di Falloppio o peritoneale primario di nuova diagnosi. |
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E.1.1.1 | Medical condition in easily understood language |
Advanced ovarian, fallopian or primary peritoneal cancer. |
Tumore avanzato ovarico, alle tube di Falloppio o peritoneale 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 | 21.1 |
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 | 21.1 |
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 | 21.0 |
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 | 21.0 |
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. |
Determinare l’efficacia di durvalumab e di olaparib valutata tramite PFS nel trattamento di prima linea di pazienti non-tBRCAm con nuova diagnosi di cancro ovarico avanzato. |
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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) |
- OS nella coorte non-tBRCAm - ORR, ORR prima dell’intervento chirurgico nel gruppo IDS, durata della risposta, PFS2, TFST, TSST e TDT nella coorte non-tBRCAm - Risultati sulla qualità della vita correlati allo stato di salute (HRQoL), stato di salute globale e sintomi del tumore ovarico nella coorte non-tBRCAm - pCR in pazienti sottoposti ad IDS nella coorte non-tBRCAm - PK and Ig di durvalumab nel campionamento della popolazione - PK di olaparib nel campionamento della popolazione - Il beneficio clinico potenziale aggiuntivo nella coorte tBRCAm (PFS, PFS2, ORR, ORR nel gruppo pre-chrirurgia, durata della risposta, TFST, TSST, TDT, HRQoL, percentuale dei pazienti con pCR in pazienti sottoposti ad IDS) |
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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 |
• Pazienti donne con nuova diagnosi, confermata istologicamente, di tumore ovarico epiteliale avanzato (Stage III-IV) di alto grado incluso alto grado serio , alto grado endometriale, tumore ovarico a cellule chiare o carcinosarcoma, tumore primario peritoneale e/o tumore alle tube di Falloppio • I pazienti devono avere età =18 anni • Tutti i pazienti possono essere sottoposti a chirurgia citoriduttiva o: chirurgia primaria anticipata o previsione di sottoporsi a chemioterapia con interval debulking surgery • Presentazione obbligatoria del campione tumorale per il test tBRCA centralizzato • Prova della presenza o dell’assenza della mutazione BRCA1/2 nel tessuto tumorale • ECOG performance status 0-1 • I pazienti devono aver preservato la funzionalità d’ organo e del midollo osseo • Lo stato di menopausa o la prova di non fertilità per le donne con potenziale fertilità: test delle urine o test sierico di gravidanza negativi |
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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 |
• Tumore ovarico non epiteliale, tumori borderline, tumori epiteliali di basso grado o istologia mucinosa • Precedente terapia antitumorale sistemica per il tumore ovarico • Precedente trattamento con PARP inibitori o terapia immuno mediata • Chemioterapia citotossica intraperitoneale pianificata • Disturbi autoimmuni o infiammatori documentati attivi o pregressi • Pazienti considerati uno scarso rischio medico a causa di una malattia seria, intercorrente incontrollata • Malattia cardiovascolare di rilevanza clinica • Storia di un'altra neoplasia maligna ad eccezione per: – Neoplasie maligne trattate con intento curativo e con nessuna malattia attiva conosciuta =5 anni prima della prima dose del trattamento di studio e di basso rischio potenziale di recidiva (i pazienti che hanno ricevuto una precedente chemioterapia adiuvante per carcinoma mammario in stadio iniziale potrebbero essere idonei, a condizione che sia stato completato =3 anni prima della registrazione e che il paziente non presenti recidive o metastasi) tumore cutaneo non-melanoma adeguatamente trattato o lentigo maligna senza evidenza di malattia -Carcinoma adeguatamente trattato in situ senza evidenza di malattia -Tumore dell'endometrio Stadio FIGO IA, Grado 1 o Grado 2 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival (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. |
Progression Free Survival (PFS) è definita come il tempo dalla randomizzazione alla coorte non-tBRCAm fino alla data della progressione oggettiva della malattia o della morte (da qualsiasi causa in assenza della progressione) indipendentemente dal fatto che il paziente si ritiri dalla terapia assegnata o riceva un’altra terapia antitumorale precedentemente alla progressione |
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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 52 months after first patient has received first dose of IP). |
• TAC (valutata in accordo ai RECIST 1.1) eseguita dal primo paziente arruolato al data cut off (all’incirca 52 mesi dopo che il primo paziente ha ricevuto la prima dose di 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 |
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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From first patient enrolled to data cut off (approximately 52 months after first patient has received first dose of IP). A final analysis of OS, PFS2, TFST, TSST, TDT will be performed at approximately 5 years following the randomisation of the last non-tBRCAm patient. |
Dal primo paziente arruolato fino al data cut off (circa 52 mesi dopo che il primo paziente ha ricevuto la prima dose di IP). Sarà effettuata un'analisi finale di OS, PFS2, TFST, TSST, TDT circa 5 anni dopo la randomizzazione dell'ultimo paziente non-tBRCAm. |
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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 |
oltre alla coorte in doppio cieco non-tBRCAm, c'è una singola coorte tBRCAm in aperto |
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 | 12 |
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 | Information not present in EudraCT |
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 |
Canada |
China |
Japan |
Korea, Republic of |
Turkey |
United States |
Austria |
Belgium |
Bulgaria |
Denmark |
Finland |
France |
Germany |
Hungary |
Italy |
Poland |
Spain |
Sweden |
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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). |
La fine dello studio è definita come il punto di cut-off dei dati per l'analisi finale della sopravvivenza globale nella coorte non-tBRCAm (approssimativamente al 50% della maturità o 5 anni dopo che l'ultimo paziente non-tBRCAm viene randomizzato al trattamento, a seconda di quale si verifica prima) |
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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 | 7 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |