NUVOLA TRIAL Open-label Multicentre Study

Inclusion Criteria:

1. Pathologically confirmed advanced high grade serous or endometrioid ovarian, fallopiantube, or primary peritoneal cancer;

2. Female, aged at least 18 years;

3. Documented mutation in BRCA1 or BRCA2 germline and/or somatic that is predicted to bedeleterious or suspected deleterious (known or predicted to be detrimental/lead toloss of function);

4. FIGO stages III-IV primary ovarian, primary peritoneal, or fallopian tube cancers notsuitable of primary cytoreductive surgery (Criteria for Neoadjuvant Chemotherapydespite to Primary Surgery: clinical conditions; Fagotti's score > 10, small bowelcarcinosis, mesenteric retraction);

5. Measurable disease according to RECIST criteria 1.1;

6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;

7. Left Ventricular Ejection Fraction (LVEF) ≥ institutional lower limit of normal;

8. Patients must have a life expectancy of >16 weeks;

9. Patients must have normal organ and bone marrow function measured within 28 days priorto administration of study treatment as defined below:

10. Haemoglobin ≥ 10.0 g/dL and no blood transfusions in the 28 days prior toentry/randomisation (choose whichever is most applicable to the study)

11. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

12. No features suggestive of MDS/AML on peripheral blood smear

13. White blood cells (WBC) > 3x109/L

14. Platelets count ≥ 100 x 109/L

15. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)

16. AST (Aspartate Aminotransferase)/ALT (Alanine aminotransferase) ≤ 2.5 xinstitutional upper limit of normal unless liver metastases are present in whichcase it must be ≤ 5x ULN

17. Creatinine clearance estimated using the Cockcroft-Gault equation of ≥51 mL/minusing the Cockcroft-Gault equation. Estimated creatinine clearance =[ (140-age [years]) x weight (kg) (x F)] /[serumcreatinine (mg/dL) x 72]; where F=0.85 for females

18. No other invasive malignancy within the past 3 years except non-melanoma skin canceror in situ cervical cancer (patients with previous cancers may be enrolled providingthat no recurrences have be reported in the last 3 years);

19. Written Informed Consent;

20. Postmenopausal status defined as: Amenorrheic for 1 year or more following cessation of exogenous hormonal treatmentsLuteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the postmenopausal range for women under 50 Radiation-induced oophorectomy with last menses >1year ago Chemotherapy-induced menopause with >1 year interval since last mensesSurgical sterilisation (bilateral oophorectomy or hysterectomy) or evidence ofnon-childbearing status for women of childbearing potential: negative urine or serumpregnancy test prior to Myriad BRCA test during screening part 1, within 28 days ofstudy treatment and confirmed prior to treatment on day 1;

21. Patient is willing and able to comply with the protocol for the duration of the studyincluding undergoing treatment and scheduled visits and examinations;

22. For inclusion in the optional exploratory genetic and the optional biomarker research,patients must provide informed consent for genetic and for biomarker research

Exclusion Criteria:

1. History of another neoplastic disease (except basal cell carcinoma or cervicalcarcinoma in situ adequately treated) unless in remission for 5 years or longer

2. Other serious illnesses, such as: Congestive heart failure or angina pectoris; myocardial infarction within 3 monthsbefore enrolment; uncontrolled arterial hypertension or arrhythmias Psychiatricdisorder that prevents compliance with protocol Uncontrolled seizures Active viralhepatitis; or chronic liver disease Active infection Any other unstable medicalconditions

3. Involvement in the planning and/or conduct of the study (applies to both AstraZenecastaff and/or staff at the study site).

4. Non defective BRCA status or BRCA 1 and/or BRCA2 mutations that are considered to benon detrimental (e.g."Variants of uncertain clinical significance" or "Variant ofunknown significance"or "Variant, favor polymorphism" or "benign polymorphism" etc)

5. Patients with early stage disease (FIGO Stage I, IIA, IIB or IIC)

6. Patients who have previously received chemotherapy or radiotherapy for any abdominalor pelvic tumour, including treatment for prior diagnosis at an earlier stage fortheir ovarian, fallopian tube or primary peritoneal cancer. (Patients who havereceived prior adjuvant chemotherapy for localised breast cancer may be eligible,provided that it was completed more than three years prior to registration, and thatthe patient remains free of recurrent or metastatic disease).

7. Patients with synchronous primary endometrial cancer, or a past history of primaryendometrial cancer, unless all of the following conditions are met: Stage not greaterthan I-A; no more than superficial myometrial invasion, without vascular or lymphaticinvasion; no poorly differentiated subtypes, including papillary serous, clear cell orother FIGO Grade 3 lesions.

8. Participation in another clinical study with an investigational product

9. Any previous treatment with PARP inhibitor, including olaparib.

10. Resting ECG with QTc (corrected QT interval) > 470 msec on 2 or more time pointswithin a 24 hour period or family history of long QT syndrome

11. Concomitant use of known potent CYP3A4 (Cytochrome P450 3A4)inhibitors such asketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin,clarithromycin and nelfinavir. The required washout period prior to starting olaparibis 2 weeks.

12. Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade 2caused by previous cancer therapy, excluding alopecia.

13. Patients with myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or withfeatures suggestive of MDS/AML.

14. Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absenceof brain metastases is not required. The patient can receive a stable dose ofcorticosteroids before and during the study as long as these were started at least 4weeks prior to treatment. Patients with spinal cord compression unless considered tohave received definitive treatment for this and evidence of clinically stable diseasefor 28 days.

15. Major surgery within 2 weeks of starting study treatment and patients must haverecovered from any effects of any major surgery.

16. Patients unable to swallow orally administered medication and patients withgastrointestinal disorders likely to interfere with absorption of the studymedication, including gastrectomy.

17. Breast feeding women.

18. Immunocompromised patients, e.g., patients who are known to be serologically positivefor human immunodeficiency virus (HIV).

19. Patients with a known hypersensitivity to olaparib or any of the excipients of theproduct.

20. Patients with a known hypersensitivity to Paclitaxel or Carboplatin, or any of theexcipients of these agents

21. Previous allogeneic bone marrow transplant, or double umbilical cord bloodtransplantation

22. Previous enrolment in the present study

23. Patients receiving any systemic chemotherapy or radiotherapy (except for palliativereasons) within 3 weeks prior to study treatment

24. Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin,rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ) ormoderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washoutperiod prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for otheragents.

25. Whole blood transfusions in the last 120 days prior to entry to the study.