BRCA or HRR+ Mutated Ovarian Cancer Patients MedDRA version: 20.0 Level: PT Classification code 10033128 Term: Ovarian cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Lynparza
Product Name: Lynparza
Product Code: AZD2281(KU-0059436)
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: olaparib
CAS Number: 763113-22-0
Current Sponsor code: AZD2281 (KU
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent prior to any study specific procedures 2. Age 18 years or over 3. Documented germline or somatic mutation in BRCA1 or BRCA2 genes that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function) [Genetic counselling for patients with germline BRCA mutations should be performed according to local regulations] or Tumour BRCAwt status and documented qualifying mutation in any of 13 genes involved in the HRR pathway, excluding BRCA1 and BRCA2 (ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L), identified by the Lynparza HRR Assay in archival tumour tissue (i.e., BRCA-independent HRRm) 4. Patients with platinum sensitive relapsed high grade epithelial ovarian cancers (including primary peritoneal and/or fallopian tube cancer): Platinum sensitive disease is defined as disease progression =6 months after completion of their last dose of platinum based chemotherapy 5. Patients should have received at least 2 previous lines of platinum containing therapy prior to enrolment: For the last chemotherapy course immediately prior to enrolment on the study, patients must be, in the opinion of the investigator, in response (partial or complete radiological response) and no evidence of a rising CA-125, following completion of this chemotherapy course. 6. Patients must have normal organ and bone marrow function measured within 28 days of enrolment, as defined below: Haemoglobin = 10.0 g/dL with no blood transfusions in the past 28 days Absolute neutrophil count (ANC) = 1.5 x 109/L Platelet count = 100 x 109/L 7. 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 ULN unless liver metastases are present in which case they must be = 5x ULN 8. Creatinine clearance > 50 ml/min (calculated) 9. Patients must be postmenopausal or have evidence of non-childbearing status for women of childbearing potential as defined in the protocol. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 138 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 137
Exclusion criteria
Exclusion criteria: 1. Patients previously diagnosed with gBRCAm disease 2. Participation in another clinical study with an investigational product during the most recent chemotherapy course 3. Patients with a known hypersensitivity to olaparib or any of the excipients of the product 4. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) or major surgery within 3 weeks prior to olaparib treatment. Major surgery within 3 weeks of starting study treatment and patients must have recovered from any effects of any major surgery 5. Persistent toxicities Common Terminology Criteria for Adverse Event (CTCAE) grade 2 caused by previous cancer therapy, excluding alopecia 6. Patients with myelodysplastic syndrome/acute myeloid leukaemia 7. Immuno-compromised patients e.g. Human Immunodeficiency Virus (HIV) requiring treatment or active Hepatitis B or C 8. Patients with symptomatic uncontrolled brain metastases. 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 (SD) for 28 days 9. Patients considered to be at a high medical risk due to a serious, uncontrolled medical disorder, systemic disease or active, uncontrolled infection. 10. Currently pregnant (confirmed with a positive pregnancy test) or breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the real world clinical effectiveness of olaparib maintenance monotherapy by investigator assessed progression free survival (PFS) according to modified Response Evaluation Criteria In Solid Tumours (RECIST) 1.1 in patients with sBRCAm ovarian cancer. To assess the real world clinical effectiveness of olaparib maintenance monotherapy by investigator assessed PFS according to RECIST 1.1 in patients with BRCAm ovarian cancer.;Secondary Objective: To assess the real world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm ovarian cancer and patients with sBRCAm ovarian cancer, by assessment of: - overall survival (OS), - time to investigator- assessed second progression (PFS2), or death. - time to first subsequent therapy or death (TFST), - time to second subsequent therapy or death (TSST) and - time to olaparib discontinuation or death (TDT) To assess and describe the following for patients with BRCAm ovarian cancer and patients with sBRCAm ovarian cancer. - quality of life (QoL) - patterns of routine clinical use of olaparib, the nature and patterns of AEs of nausea and vomiting and their impact on QoL - safety and tolerability of olaparib maintenance monotherapy To describe nausea/vomiting toxicity management patterns used in routine clinical practice.;Primary end point(s): PFS (Progression Free Survival) is defined as the time from enrolment until the date of objective radiological disease progression (assessed via RECIST 1.1) or death (by any cause in the absence of disease progression) regardless of whether the patient withdraws from therapy or receives another anticancer therapy prior to disease progression. Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable efficacy assessment. However, if the patient progresses or dies after two or more missed visits, the patient will be censored at the time of the lat | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall Survival (OS) Overall survival is defined as the time from the date of enrolment in the study until death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive. Time from enrolment to second progression (PFS2) Time from enrolment to second progression is defined as the time from the date of enrolment to the earliest of the progression event subsequent to that used for the primary variable PFS or death. The date of second progression will be recorded by the investigator and defined according to local standard clinical practice and may involve any of objective radiological, symptomatic, CA-125 progression or death. Second progression status will be reviewed every 12 weeks following the progression event used for the primary variable PFS (the first progression) and status recorded. Patients alive and for whom a second disease progression has not been observed should be censored at the last time known to be alive and without a second disease progression, i.e. censored at the last assessment for progression date if the patient has not had a second progression or death). Time to first subsequent anti-cancer therapy or death (TFST) As a supportive summary to PFS, time to start of first subsequent anti-cancer therapy or death will be assessed. Time to first subsequent therapy or death is defined as the time from the date of enrolment to the earlier of first subsequent therapy start date, or death date. Any patient not known to have had a further subsequent therapy or death will be censored at the last known time to have not received subsequent anti-cancer therapy. Time to study treatment discontinuation or death (TDT) Time to study treatment discontinuation or death (TDT) will be assessed. TDT is defined as the time from the date of enrolment to the earlier of the date of study treatment discontinuation or death. Any pat | — |
Countries
Bulgaria, Canada, Czech Republic, Hungary, Italy, Poland, Spain, United Kingdom
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed