OLAPARIB for High-grade serous ovarian cancer | Endometrioid ovarian cancer | Fallopian tube cancer | Primary peritoneal cancer

Inclusion criteria

• {"criterion_text":"- Females ≥18 years of age (at the time informed consent is obtained)."}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status 0-1 within 14 days before enrolment (see Appendix B)."}
• {"criterion_text":"- Patients must have a life expectancy ≥ 16 weeks."}
• {"criterion_text":"- Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients within 72 hours of receiving the first dose of study medication. Postmenopausal is defined as:  Amenorrhoeic 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)"}
• {"criterion_text":"- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol."}
• {"criterion_text":"- Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses."}
• {"criterion_text":"- Patient with newly diagnosed high- grade serous or endometrioid ovarian cancer, primary peritoneal cancer and/or fallopian-tube cancer at an advanced stage: FIGO stage III or IV of the 2014 FIGO classification (see Appendix A)."}
• {"criterion_text":"- Patient who has completed prior to enrolment first line platinum-taxane chemotherapy: a. Platinum-taxane based regimen must have consisted of a minimum of 6 treatment cycles and a maximum of 8. However, if platinum-based therapy must be discontinued early as a result of non-haematological toxicity specifically related to the platinum regimen, (i.e., neurotoxicity, hypersensitivity etc.), the patient must have received a minimum of 4 cycles of the platinum regimen. b. Patient must have received prior to enrolment a minimum of 3 cycles of Bevacizumab in combination with the 3 last cycles of platinum-based chemotherapy. Only in case of interval debulking surgery, it is allowed to have received only 2 cycles of Bevacizumab in combination with the last 3 cycles of platinum-based chemotherapy. c. Patients must not have received an investigational agent during their first line course of chemotherapy."}
• {"criterion_text":"- Patient must be prior to enrolment without evidence of disease (NED) or in complete response (CR) or partial response (PR) from the first-line treatment. There should be no clinical evidence of disease progression (physical exam, imagery, CA-125) throughout her first-line treatment and prior to study enrolment. ‘Response’ is used throughout the protocol and refers to patients being, in the opinion of the Investigator, in clinical CR or PR on the post-treatment scan (at the end of platinum-based chemotherapy). Clinical CR is defined as no evidence of RECIST measurable or nonmeasurable disease on the post-treatment scan and a normal CA-125. PR is defined as ≥30% reduction in tumour volume demonstrated from the start to finish of chemotherapy OR no evidence of RECIST measurable disease on the post-treatment scan with a CA-125 which has not decreased to within the normal range."}
• {"criterion_text":"- Patient must be included at least 4 weeks and no more than 8 weeks after her last dose of chemotherapy (last dose is the day of the last infusion) and all major toxicities from the previous chemotherapy must have resolved to CTCAE grade 1 or better (except alopecia and peripheral neuropathy)."}
• {"criterion_text":"- Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary cancer must be available for central HRD testing and test result must be available before inclusion"}
• {"criterion_text":"- Patients must have normal organ and bone marrow function measured within 7 days prior to administration of study treatment as defined below:  Haemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days  Absolute neutrophil count (ANC) ≥ 1.5 x 109/L  Platelet count ≥ 100 x 109/L  Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be ≤ 5x ULN  Patients must have creatinine clearance estimated of ≥51 mL/min using the Cockcroft-Gault equation or based on a 24-hour urine test: Estimated creatinine clearance = (140-age [years]) x weight (kg) (x F)a serum creatinine (mg/dL) x 72 a where F=0.85 for females  Urine dipstick for proteinuria <2+. Patients discovered to have 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate <1 g of protein in 24 hours or urine protein/creatinine (UPC) ratio ≤1.0"}

Exclusion criteria

• {"criterion_text":"- Epithelial ovarian cancer with histologies as clear cell, carcinosarcoma or undifferentiated cancer."}
• {"criterion_text":"- Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or Sub- Arachnoids Hemorrhage (SAH) within 6 months prior to enrolment."}
• {"criterion_text":"- History or evidence of haemorrhagic disorders within 6 months prior to enrolment."}
• {"criterion_text":"- History or clinical suspicion of brain metastases or spinal cord compression."}
• {"criterion_text":"- nt traumatic injury during 4 weeks prior to enrolment."}
• {"criterion_text":"- Non-healing wound, active ulcer, or bone fracture."}
• {"criterion_text":"- History of VEGF therapy related abdominal fistula or gastrointestinal perforation or active gastrointestinal bleeding within 6 months prior to the first study treatment."}
• {"criterion_text":"- Current, clinically relevant bowel obstruction, including sub-occlusive disease, related to underlying disease."}
• {"criterion_text":"- Patient with evidence of abdominal free air not explained by paracentesis or recent surgical procedure."}
• {"criterion_text":"- Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the Investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation >500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome."}
• {"criterion_text":"- Persistent toxicities (> CTCAE grade 2) caused by previous cancer therapy, excluding alopecia."}
• {"criterion_text":"- Non-epithelial origin of the ovary, the fallopian tube or the peritoneum (i.e., germ cell tumours)."}
• {"criterion_text":"- Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent."}
• {"criterion_text":"- Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication."}
• {"criterion_text":"- Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV)."}
• {"criterion_text":"- Patients with known active hepatitis (i.e., Hepatitis B or C).  Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible.  Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA."}
• {"criterion_text":"- Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John’s Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents."}
• {"criterion_text":"- Concomitant use of known strong CYP3A inhibitors (eg, itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg, ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks."}
• {"criterion_text":"- Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)."}
• {"criterion_text":"- Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable)."}
• {"criterion_text":"- Ovarian tumours of low malignant potential (e.g., borderline tumours) or mucinous carcinoma."}
• {"criterion_text":"- Patients with a known hypersensitivity to the study treatment (i.e., olaparib and bevacizumab) or any of the excipients of the products."}
• {"criterion_text":"- Involvement in the planning and/or conduct of the study."}
• {"criterion_text":"- Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements."}
• {"criterion_text":"- Previous enrolment in the present study."}
• {"criterion_text":"- Breastfeeding women."}
• {"criterion_text":"- Other malignancy unless curatively treated with no evidence of disease for ≥5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma."}
• {"criterion_text":"- Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery."}
• {"criterion_text":"- Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment."}
• {"criterion_text":"- Any previous treatment with PARPi, including olaparib."}
• {"criterion_text":"- Prior history of hypertensive crisis (CTCAE grade 4) or hypertensive encephalopathy."}
• {"criterion_text":"- Clinically significant (e.g., active) cardiovascular disease, including: a. Myocardial infarction or unstable angina within ≤ 6 months of enrolment, b. New York Heart Association (NYHA) ≥ grade 2 congestive heart failure (CHF) (see Appendix C). c. Poorly controlled cardiac arrhythmia despite medication (patient with rate controlled atrial fibrillation are eligible), or any clinically significant abnormal finding on resting ECG, d. Peripheral vascular disease grade ≥ 3 (e.g., symptomatic and interfering with activities of daily living [ADL] requiring repair or revision)."}

Primary endpoints

• {"endpoint_text":"- Percentage of HR status agreement between VHIO-CARD-300 test and SOPHiA DDM™ Dx HRD Solution. The corresponding 95% confidence intervals (CI) will be reported.","definition_or_measurement_approach":"Percentage agreement between VHIO-CARD-300 and SOPHiA DDM™ Dx HRD Solution; corresponding 95% confidence intervals will be reported."}

Secondary endpoints

• {"endpoint_text":"- Sensitivity, specificity, predictive positive and negative value of the VHIO-CARD-300 test, using SOPHiA DDM™ Dx HRD Solution as a reference test.","definition_or_measurement_approach":"Diagnostic accuracy metrics (sensitivity, specificity, positive predictive value, negative predictive value) of VHIO-CARD-300 compared to SOPHiA DDM™ Dx HRD Solution as reference."}
• {"endpoint_text":"- Progression free survival (PFS) and overall survival (OS) will be analysed in HRD and HRP groups, as determined by the VHIOCARD- 300 test. PFS: time from the date of enrolment to the date of first documentation of disease progression or death due to any cause, whichever occurs first. OS: time from the date of enrolment to the date of death due to any cause. The progression of disease will be assessed by the Investigator according to the modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1) will be used.","definition_or_measurement_approach":"PFS defined as time from enrolment to first documented progression or death; OS defined as time from enrolment to death from any cause. Progression assessed by Investigator per modified RECIST 1.1."}
• {"endpoint_text":"- PFS and OS will be analysed in discrepant cases (i.e., HRD positive by VHIO-CARD- 300 test but HRD negative by SOPHiA DDM™ Dx HRD Solution and HRD negative by VHIO-CARD-300 test but HRD positive by SOPHiA DDM™ Dx HRD Solution).","definition_or_measurement_approach":"Analysis of PFS and OS in cases with discordant HRD classifications between the two tests using the same PFS/OS definitions as above."}
• {"endpoint_text":"- Percentage of inconclusive results will be estimated for each test","definition_or_measurement_approach":"Estimate proportion of inconclusive test results for each assay (VHIO-CARD-300 and SOPHiA DDM™ Dx HRD Solution)."}
• {"endpoint_text":"- Assessment of adverse events (AEs) graded by the National Cancer Institute (NCI) CTCAE v5.0, serious adverse events (SAEs), abnormal vital signs, abnormal ECG results, and evaluation of laboratory parameters.","definition_or_measurement_approach":"Safety assessed by recording AEs graded per NCI CTCAE v5.0, SAEs, abnormal vitals, ECGs, and laboratory parameter evaluations."}

Spain

Earliest CTIS Part Ii Submission Date

07-11-2024

Latest Decision Or Authorization Date

13-04-2026

Processing Time Days

522

Number Of Sites

14

Number Of Participants

100

Primary sponsor

Full Name

Vall D Hebron Institute Of Oncology

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Spain

Third parties

• {"country":"Spain","full_name":"Astrazeneca Farmaceutica Spain S.A.","duties_or_roles":"Drug provider","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Hospital Universitario Fundacion Jimenez Diaz","duties_or_roles":"4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Sophia Genetics Inc.","duties_or_roles":"In vitro CEE marked diagnostic test provider","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Distefar Del Sur S.L.","duties_or_roles":"14","organisation_type":"Pharmaceutical company"}