E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
BRCA Mutated Platinum Sensitive Relapse (PSR) high grade Serous Ovarian Cancer |
Carcinoma ovarico BRCA mutato, platino sensibile recidivato |
|
E.1.1.1 | Medical condition in easily understood language |
Ovarian cancer |
Carcinoma ovarico |
|
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 | 10014733 |
E.1.2 | Term | Endometrial 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 | 14.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033128 |
E.1.2 | Term | Ovarian cancer |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Determine the efficacy by progression free survival of olaparib maintenance monotherapy compared to placebo in BRCA mutated relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy. |
Determinare l’efficacia, valutando la Progression Free Survival (PFS) (usando la revisione centralizzata indipendente in cieco – BICR - in accordo ai criteri RECIST 1.1), della monoterapia di mantenimento con Olaparib comparata a placebo in pazienti affette da carcinoma ovarico recidivato BRCA mutato che sono in risposta completa o parziale in seguito alla chemioterapia a base di platino |
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E.2.2 | Secondary objectives of the trial |
1. Efficacy in patients following Platinum Based Chemotherapy by assessment of overall survival
2. Efficacy in patients following Platinum Based Chemotherapy by assessment of time to earliest progression by RECIST or Cancer Antigen (CA-125)
3. Efficacy in patients following Platinum Based Chemotherapy by assessment of time to earliest progression by RECIST or Efficacy in patients following Platinum Based Chemotherapy by assessment of time from randomisation to second progression
4. Time to deterioration of Health-Related Quality of Life (HRQoL) as assessed by TOI and FACT-O
5. Efficacy in patients with a deleterious or suspected deleterious variant in either of the BRCA genes by assessment of PFS.
6. To determine the exposure to Olaparib
7. Safety and tolerability of olaparib by assessment of the number of AEs and review of laboratory parameters
|
1. Efficacia a seguito alla chemioterapia a base di platino, valutando la sopravvivenza globale OS
2. Efficacia a seguito alla chemioterapia a base di platino, valutando il tempo alla prima progressione secondo RECIST o l’antigene CA-125.
3. Efficacia a seguito alla chemioterapia a base di platino, valutando il tempo dalla randomizzazione alla seconda progressione
4. Tempo al peggioramento dell’ Health-related Quality of Life (HRQoL) valutato tramite il Trial Outcome Index (TOI) e il Functional Assessment of Cancer Therapy – Ovarian (FACT-O).
5.Efficacia in pazienti con una variante deleteria o sospetta deleteria in uno dei due geni BRCA mediante valutazione PFS
6.Determinare l’esposizione a Olaparib
7.Valutare la sicurezza e la tollerabilità di Olaparib valutando n di EAs e analizzando i parametri di laboratorio |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients must be ≥ 18 years of age.
• Female patients with histologically diagnosed relapsed high grade serous ovarian cancer (including primary peritoneal and / or fallopian tube cancer) or high grade endometrioid cancer.
• Documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss
of function).
• Patients who have received at least 2 previous lines of platinum containing therapy prior to randomisation For the penultimate chemotherapy course prior to enrolment on the study:
• Patient defined as platinum sensitive after this treatment; defined as disease progression greater than 6 months after completion of their last dose of platinum chemotherapy For the last chemotherapy course immediately prior to randomisation on the study:
• Patients must be, in the opinion of the investigator, in response (partial or complete radiological response), or may have no evidence of disease (if optimal cytoreductive surgery was conducted prior to chemotherapy), and no evidence of a rising CA-125, following completion of this chemotherapy course
• Patient must have received a platinum based chemotherapy regimen carboplatin or cisplatin) and have received at least 4 cycles of treatment |
• Le pazienti devono avere piu di 18 anni di età.
• Le pazienti con diagnosi istologica di carcinoma ovarico recidivato sieroso ad alto grado (compresi peritoneale primario e / o il cancro tube di Falloppio) o tumore all' endometrio ad alto grado.
• Mutazione documentata nei geni BRCA1 o BRCA2 che si prevede essere deleteria o sospetto deleteria (nota o stimata di essere dannoso / portante alla perdita di funzione).
• I pazienti che hanno completato almeno 2 linee di terapia a base di platino prima della randomizzazione e devono essere considerate sensibili al platino dopo la penultima chemioterapia
• Pazienti definite platino sensibile dopo questo trattamento, con progressione di amlattia che si amnifesta dopo più di 6 mesi dall' ultimo ciclo di chemioterapia con platino per l'ultimo ciclo di chemioterapia immediatamente prima della randomizzazione dello studio.
• pazienti devono essere, a giudizio dello sperimentatore, in risposta (risposta radiologica parziale o totale), oppure non avere nessuna evidenza di malattia (se la chirurgia citoriduttiva è stato praticata prima della chemioterapia), e nessuna evidenza di un CA-125 aumento, a seguito del completamento di questo ciclo di chemioterapia
• pazienti devono avere ricevuto un ciclo completo di chemioterapia con platino (a base di carboplatino o cisplatino) e devono avere ricevuto almeno 4 cicli di trattamento. |
|
E.4 | Principal exclusion criteria |
• Involvement in the planning and/or conduct of the study (applies to
both AstraZeneca staff and/or staff at the study site).
• BRCA 1 and/or BRCA2 mutations that are considered to be non detrimental (e.g., “Variants of uncertain clinical significance” or “Variant of unknown significance” or “Variant, favor polymorphism” or “benign polymorphism” etc.)
• Patients who have had drainage of their ascites during the final 2 cycles of their last chemotherapy regimen prior to enrolment on the study. |
• Coinvolgimento nella pianificazione e / o conduzione dello studio (si applica sia a personale AstraZeneca e / o a personale del centro di studio).
• mutazioni dei geni BRCA 1 e / o BRCA2 che sono considerate essere non dannose (ad esempio, Varianti di significato clinico incerto, Variante di significato sconosciuto, polimorfismo benigno, etc)
• pazienti che hanno avuto drenaggio di asciti durante gli ultimi 2 cicli di chemioterapia prima dell'arruolamento nello studio. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival (PFS) by central review of RECIST data. |
Sopravvivenza libera da progressione (PFS) secondo revisione centralizzata dei dati RECIST.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Radiologic scans performed at base line then every ~12 weeks up to 72 weeks, then every ~ 24 weeks thereafter until objective radiological disease progression.
Study data collection expected to last until 2018. |
Scansioni Radiologiche eseguite al baseline e poi ogni ~ 12 settimane fino a 72 settimane, poi ogni ~ 24 settimane fino oggettiva, determinata radiologicamente, progressione della malattia .
La raccolta dei dati di studio dovrebbe durare fino al 2018.
|
|
E.5.2 | Secondary end point(s) |
1. Efficacy in patients following Platinum Based Chemotherapy by assessment of overall survival
2. Efficacy in patients following Platinum Based Chemotherapy by assessment of time to earliest progression by RECIST or Cancer Antigen (CA-125) or death
3. Efficacy in patients following Platinum Based Chemotherapy by assessment of time from randomisation to second progression
4. Time to deterioration of Health-Related Quality of Life (HRQoL) as assessed by TOI and FACT-O
5. Efficacy in patients with a deleterious or suspected deleterious variant in either of the BRCA genes by assessment of PFS.
6. To determine the exposure to Olaparib by Pharmacokinetic analysis
7. Safety and tolerability of olaparib by assessment of the number of AEs and review of laboratory parameters |
1. Efficacia a seguito alla chemioterapia a base di platino, valutando la sopravvivenza globale OS
2. Efficacia a seguito alla chemioterapia a base di platino, valutando il tempo alla prima progressione secondo RECIST o l’antigene CA-125 o la morte
3. Efficacia a seguito alla chemioterapia a base di platino, valutando il tempo dalla randomizzazione alla seconda progressione
4. Tempo al peggioramento della qualità di salute e di vita (HRQoL) valutato tramite il Trial Outcome Index (TOI) e il Functional Assessment of Cancer Therapy – Ovarian (FACT-O).
5.Efficacia in pazienti con una variante deleteria o sospetta deleteria in uno dei due geni BRCA mediante valutazione PFS
6.Determinare l’esposizione a Olaparib mediante analisi farmacocinetiche
7.Valutare la sicurezza e la tollerabilità di Olaparib valutando numero di eventi avversi e analizzando i parametri di laboratorio |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Data collection expected until 2018, for all except Pk endpoint 6.
1. Survival assessed every 4 wks until treatment discontinues, then every 12 wks.
2. CA-125, baseline then every 4 wks. Radiological scans, base line, every ~12 wks until obj radiological disease prog
3. Radiologic scans, baseline, every 12 wks for 72 wks, every 24 wks until 1st prog. As per local practice until 2nd prog
4. Paper Q's at baseline, Day 29 then in line with RECIST, until disease prog
5. Radiological scans baseline, every ~12 wks for 1st 72 wks, every ~24 wks, until disease prog
6. Pk in a subset of patients. Sample times: Day 1+15 pre-dose & 1 hr; Day 29 pre-dose, 0.5-1, 1-3, 3-6 and 6-12 hrs.
7. AEs from inf cons until post treatment 30-day follow-up period. Labs until treatment discontinued. |
1. Sopravvivenza ogni 4 sett fino a fine del trattamento, poi ogni 12 sett. 2. CA-125, al basale poi ogni 4 settimane. Scansioni radiologiche al basale,ogni ~ 12 sett fino a obiettiva progressione di malattia. 3. Scansioni radiologiche al basale, ogni 12 sett per 72 setti, ogni 24 sett fino alla 1 ° prog. Come da pratica clinica locale fino al 2° prog. 4. questionari al basale, al gg 29 poi secondo criteri RECIST, fino a progr di malattia 5. Scansioni radiologiche al basale, ogni ~ 12 sett per prime 72 sett, ogni ~ 24 sett, fino al prog malattia 6. PK in un gruppo di pazienti. Tempistiche del campione: Giorno 1+15 pre-dose e 1 ora; Giorno 29 pre-dose, 0,5-1, 1-3, 3-6 e 6-12 ore.
7. Eventi avversi fino a 30 giorni dopo di trattamento. Valori di laboratorio fino a fine trattamento. |
|
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) | 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 | No |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 39 |
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 |
China |
France |
Germany |
Italy |
Japan |
Netherlands |
Poland |
Russian Federation |
Spain |
Sweden |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
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 (last visit last subject) undergoing the study |
LVLS |
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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 | 9 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |