This is a prospective, open-label, single arm, multi-center study to assess the real world
clinical effectiveness and safety of olaparib maintenance monotherapy as the capsule
formulation (in line with the EU approved prescribing information) and will be conducted in
platinum-sensitive relapsed high grade epithelial ovarian cancer patients (including patients
with primary peritoneal and / or fallopian tube cancer) who carry germline or somatic BRCA
mutations (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]).
The study will recruit approximately 250 patients with sBRCAm disease or gBRCAm disease, with
the aim to accrue a minimum of 50 patients with sBRCAm disease.
Patients with an unknown germline BRCA mutated status or gBRCAwt disease or previously
identified as having a BRCAm disease by a tumour test will be considered for screening and
will undergo, upon informed consent signature, central tumor and blood testing to determine
their BRCA mutation status. In addition to central BRCA testing, patients screened for the
study with unknown BRCA status or with known gBRCAwt status, for whom an adequate archival
tumour tissue sample is available, will be tested for qualifying HRR gene alterations.
Patients confirmed to carry a deleterious or suspected deleterious BRCA-independent genetic
alteration in any of 13 genes involved in the Homologous Recombination Repair (HRR) pathway
(HRRm cohort) will be allowed into an additional exploratory cohort (HRRm cohort). It is
expected that approximately 25 patients will be included in the HRRm cohort before the target
number of 250 patients with BRCAm disease is reached.
Patients will be assigned olaparib capsules orally 400 mg twice daily. They should initiate
olaparib treatment within 8 weeks after their last dose of platinum-containing chemotherapy
(last dose is the day of the last infusion) and will be assessed every 4 weeks whilst on
treatment.
All patients will have clinical and objective radiological tumour assessments according to
modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines at baseline and
every 12 weeks relative to date of enrolment, until objective radiological disease
progression as determined by the investigator. Patients could continue to receive olaparib
for as long as determined by the investigator, until objective radiological disease
progression or as long as in the investigator's opinion they are benefiting from treatment in
relation to other clinical assessments and they do not meet any other discontinuation
criteria. Once a patient has discontinued olaparib she will be managed as per local clinical
practice but will remain in the study and data will be collected on subsequent treatments,
progression, overall survival and safety.
For exploratory analysis purposes, patients will be asked to provide consent to:
1. Optional tumour samples at baseline and at disease progression
2. An optional blood sample only for patients with a confirmed sBRCAm or HRRm disease
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.
Postmenopausal is defined as any of the following:
- Amenorrhoea for 1 year or more following cessation of exogenous hormonal treatments
- For women under 50 years old, luteinizing hormone (LH) and follicle stimulating
hormone (FSH) levels in the post-menopausal range
- Radiation-induced oophorectomy, with interval of 1 year or more since last menses
- Chemotherapy-induced menopause, with interval of 1 year or more since last menses
- Surgical sterilisation (bilateral oophorectomy or hysterectomy).
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.
