A randomised, double-blind, parallel group, placebo-controlled multi-centre Phase III study to assess the efficacy and safety of olaparib versus placebo as adjuvant treatment in patients with germline BRCA1/2 mutations and high risk HER2 negative primary breast cancer who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy.

Breast cancer is a life-threatening disease and is the second leading cause of
cancer death among women.
Approximately 5% of breast cancers are associated with a mutation in the BRCA1
and/or BRCA2 gene with approximately 3% associated with the BRCA1 gene
(generally presenting with TNBC phenotype) and approximately 2% associated with
the BRCA2 gene (generally ER/PgR positive phenotype). In the general
population, BRCA mutation carriers have an increased relative risk of breast
cancer. Although there are phenotypic differences in breast cancers resulting
from BRCA1 or BRCA2 mutations, their important commonality is that mutations in
either gene result in tumours that are deficient in homologous recombination,
making both appropriate for treatment with PARP inhibitors whereby the process
of synthetic lethality can be exploited.
Olaparib (AZD2281) is a new agent that inhibits the protein called PARP. PARP
allows DNA repair. Cancer is often caused by genetic abnormality and if that
happens, the PARP activity can be increased. Olaparib can inhibit or block the
activity of PARP, and has the potential to be effective, both as a single agent
or in combination with chemotherapy. Olaparib can prevent the survival of
cancer cells because the repair meganism of damaged DNA is prevented, so that
the cancer cells die.
This Phase III study will investigate the efficacy and safety of olaparib
administered as adjuvant therapy in patients with germline BRCA1/2 mutations
and high risk HER2 negative primary breast cancer who have completed definitive
local treatment and neoadjuvant or adjuvant chemotherapy or of when olaparib
together with the hormaonal therapy (ER/PgR-positive patients)received.

This study has been transitioned to CTIS with ID 2024-511096-15-00 check the CTIS register for the current data.

To assess the safety and tolerability of adjuvant treatment with olaparib

Phase 3, randomised, double-blind, parallel group, placebo-controlled
multi-centre
Randomisation 1:1 with Olaparib 300 mg twice daily or Placebo twice daily 12
months treatment

Treatment with Olaparib 300 mg or Placebo.

Patient will get a mammogram (patients older than 50 years) or breast MRI scan
(patients younger than 50 years) every 6 months after start study treatment.
Assessments will be done on a regular base, like physical examination, vital
signs, blood sampling, ECGs and questionnaires. Pregnancy or breastfeeding is
not allowed. The risks associated with the use of olaparib are: Anemia,
neutropenea, lymphopenia, thrombocytopenie, heartburn, nausea, dizziness,
diarrhea, vomiting and fatigue.