ADVANCED OVARIAN CANCER MedDRA version: 21.1 Level: PT Classification code 10054913 Term: Serous cystadenocarcinoma ovary System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Olaparib
Product Code: [L01XX46]
Pharmaceutical Form: Tablet
INN or Proposed INN: OLAPARIB
CAS Number: 763113-22-0
Current Sponsor code: azd 2281
Concentration unit: mg milligram(s)
Conc
Sponsors
FONDAZIONE POLICLINICO UNIVERSITARIO AGOSTINO GEMELLI IRCCS UNIVERSITA' CATTOLICA DEL SACRO CUORE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: criteria: 1. Pathologically confirmed advanced high grade serous or endometrioid ovarian, fallopian tube, 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 be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function); 4. FIGO stages III-IV primary ovarian, primary peritoneal, or fallopian tube cancers not suitable of primary cytoreductive surgery (Criteria for Neaodjuvant Chemotherapy despite to Primary Surgery: clinical conditions; Fagotti score > 8, small bowel carcinosis, mesenteric retraction); 5. Measurable disease according to RECIST criteria 1.1; 6. 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 prior to administration of study treatment as defined below: a. Haemoglobin = 10.0 g/dL and no blood transfusions in the 28 days prior to entry/randomisation (choose whichever is most applicable to the study) b. Absolute neutrophil count (ANC) = 1.5 x 109/L c. No features suggestive of MDS/AML on peripheral blood smear d. White blood cells (WBC) > 3x109/L e. Platelets count = 100 x 109/L f. Total bilirubin = 1.5 x institutional upper limit of normal (ULN) g. AST (SGOT)/ALT (SGPT) = 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be = 5x ULN h. Creatinine clearance estimated using the Cockcroft-Gault equation of =51 mL/min using the Cockcroft-Gault equation. Estimated creatinine clearance =[ (140-age [years]) x weight (kg) (x F)] /[serum creatinine (mg/dL) x 72]; where F=0.85 for females 10. No other invasive malignancy within the past 3 years except non-melanoma skin cancer or in situ cervical cancer (patients with previous cancers may be enrolled providing that no recurrences have be reported in the last 3 years); 11. Written Informed Consent; 12. Postmenopausal status defined as: • Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments • Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50 • Radiation-induced oophorectomy with last menses >1 year ago • Chemotherapy-induced menopause with >1 year interval since last menses • Surgical sterilisation (bilateral oophorectomy or hysterectomy) or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test during screening part 1, within 28 days of study treatment and confirmed prior to treatment on day 1; 13. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations; 14. For inclusion in the optional exploratory genetic and the optional biomarker research, patients must provide informed consent for genetic and for biomarker research Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: Patients should not enter the study if any of the following exclusion criteria are fulfilled: 1. History of another neoplastic disease (except basal cell carcinoma or cervical carcinoma in situ adequately treated) unless in remission for 3 years or longer 2. Other serious illnesses, such as: • Congestive heart failure or angina pectoris; myocardial infarction within 3 months before enrolment; uncontrolled arterial hypertension or arrhythmias • Psychiatric disorder that prevents compliance with protocol • Uncontrolled seizures • Active viral hepatitis; or chronic liver disease • Active infection • Any other unstable medical conditions 3. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). 4. Non defective BRCA status or 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) 5. Patients with early stage disease (FIGO Stage I, IIA, IIB or IIC) 6. Patients who have previously received chemotherapy or radiotherapy for any abdominal or pelvic tumour, including treatment for prior diagnosis at an earlier stage for their ovarian, fallopian tube or primary peritoneal cancer. (Patients who have received prior adjuvant chemotherapy for localised breast cancer may be eligible, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease). 7. Patients with synchronous primary endometrial cancer, or a past history of primary endometrial cancer, unless all of the following conditions are met: Stage not greater than I-A; no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell or other 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 > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome 11. Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir. The required washout period prior to starting olaparib is 2 weeks. 12. Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade 2 caused by previous cancer therapy, excluding alopecia. 13. Patients with myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML. 14. Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days. 15. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery. 16. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication, including gastrectomy. 17. Breast feeding w
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •Pathological complete response after 3 cycles of NACT including Olaparib and weekly Carboplatin-Paclitaxel in BRCAmut advanced HGSOC women.;Secondary Objective: To determine the Objective Response Rate (ORR), defined as the percentage of patients with an objective response as determined by RECIST 1.1;;Primary end point(s): The study primary endpoint will be the complete pathological response, defined as absence of residual neoplastic cells in all the surgical specimens, including the adnexa.;Timepoint(s) of evaluation of this end point: 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - To determine the Objective Response Rate (ORR), defined as the percentage of patients with an objective response as determined by RECIST 1.1; - To determine the rate of optimal surgical cytoreduction (SCR) at interval debulking surgery; - To assess tumour response to paclitaxel plus carboplatin with olaparib as measured by CA-125 tumour marker during the neoadjuvant treatment and after debulking surgery; - To determine the tolerability and toxicity grade experienced by each patient, for each toxicity, according to NCI-CTCAE v. 4.0; Progression-free survival duration is defined as the time elapsed between treatment initiation and tumour progression assessed by RECIST or death from any cause, whichever occurs first. Overall Survival (OS), defined in each patient will be calculated from the date of the first dose of study treatment to death from any cause.;Timepoint(s) of evaluation of this end point: 2 years | — |
Countries
Italy
Contacts
Public ContactDirezione Scientifica IRCCS
Margherita Zona
Outcome results
None listed