This open label, multi-centre phase IIIb study will assess the effectiveness, benefits and
potential harms in the use of olaparib monotherapy treatment for patients with HER2-ve
metastatic breast cancer associated with Germline breast cancer susceptibility gene
(gBRCA1/2) mutations.
The study (LUCY) is a phase IIIb, multicenter, single-arm, open-label study designed to
evaluate the clinical effectiveness in a real-world setting of olaparib monotherapy in
patients with confirmed germline Breast Cancer susceptibility gene (gBRCA1/2) mutations. This
study will generate additional data to support other olaparib studies, which may help inform
and guide clinical practice. Physician defined progression-free survival is the primary
outcome measure. Overall Survival will also be assessed and the data will be statistically
compared with that from an observational study to analyze the comparative life prolongation
attributed to olaparib therapy in patients with human epidermal growth factor receptor 2
(HER2-ve), gBRCA1/2 mutation-positive metastatic breast cancer. Based on the prevalence of
gBRCA1/2 mutations, it is estimated that up to 2500 patients may require screening in order
to identify 250 patients. Patients will be administered two olaparib 150mg tablets in morning
and evening of every day after a light meal. Dose reductions may be required for olaparib
treatment related toxicities. Patients should continue to receive study treatment until
documented physician-defined disease progression as assessed by the Investigator or
unacceptable toxicity, or for as long as they do not meet any other discontinuation criteria.
A positive benefit/risk profile is expected and no ethical issues are identified from
exposing patients to olaparib within the planned clinical study.
Inclusion Criteria
1) Provision of informed consent prior to any study specific procedures. For patients aged
<20 years and screened in Japan, a written informed consent should be obtained from the
patient and his or her legally acceptable representative.
2) Patients must be ≥18 years of age. 3) Histologically or cytologically confirmed HER2-ve
breast cancer with evidence of metastatic disease. Patients can have either TNBC (defined
as oestrogen receptor and progesterone receptor negative [immunohistochemistry nuclear
staining <1%] and HER2-ve [immunohistochemistry 0, 1+ or 2+ and/or in situ hybridization
non-amplified with ratio less than 2.0]) or oestrogen receptor / progesterone receptor
positive breast cancer as long as they are HER2-ve.
4) Documented BRCA1/2 (+ve) status, the patient must have a mutation that is predicted to
be deleterious or suspected deleterious (known or predicted to be detrimental / lead to
loss of function). Mutations that are not clearly pathogenic will be assessed by a
committee of genetic specialists to adjudicate if the patient is eligible.
5) Patients must have received a taxane or an anthracycline in either an adjuvant (may
include neoadjuvant) or metastatic treatment setting. 6) Patients must not have received
more than one prior line of chemotherapy in the metastatic setting. If a patient has
oestrogen receptor and/or progesterone receptor positive HER2 negative metastatic breast
cancer and has completed a prior line of hormonal treatment, then if the current or
currently planned choice of treatment for the patient does not include a hormonal treatment
then they would be a suitable patient to enter the study. Previous endocrine therapy could
be in either an adjuvant or a metastatic setting and include endocrine therapy in
combination with a targeted agent such as a CDK4/6 or mTOR inhibitor.
7) Be considered suitable, by the Investigator, for further treatment with single-agent
chemotherapy for the metastatic disease.
8) Patients must have a life expectancy ≥ 16 weeks. Exclusion Criteria
1. Previous enrolment in the present study.
2. Participation in another clinical study with an investigational product (IP) during
the last 1 month.
3. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative
reasons) within 3 weeks prior to study treatment.
4. Any previous treatment with a PARP inhibitor, including olaparib.
5. Other malignancy within the last 5 years except: any breast cancer not considered HER2
-ve/gBRCAm, 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, or other solid tumours including lymphomas (without bone marrow
involvement) curatively treated with no evidence of disease for ≥5 years.
6. Resting electrocardiogram (ECG) with corrected QT interval (QTc) > 470 msec on two or
more time points within a 24-hour period or family history of long QT syndrome.
7. Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin,
rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or
moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The required washout
period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3
weeks for other agents.
8. Patients with myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with
features suggestive of MDS/AML.
9. Patients with symptomatic uncontrolled brain metastases. Patients with previously
treated stable brain metastases are eligible.
10. Patients with known active hepatitis (B or C) due to risk of transmitting the
infection through blood or other body fluids.
11. Previous allogenic bone marrow transplant or double umbilical cord blood
transplantation (dUCBT).
12. Whole blood transfusions in the last 120 days prior to entry to the study (packed red
blood cells and platelet transfusions are acceptable).
