MA.36 (OlympiA) trial: A Randomised, Double-Blind, Parallel group, Placebo-Controlled Multicenter 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
In breast cancer, there are differences between BRCA1 and BRCA2 mutation carriers. Approximately
70% breast cancer patients with BRCA1 mutations present as triple negative breast cancer (TNBC). In contrast, patients carrying mutations in the BRCA2 gene are more likely to be ER positive, while approximately 20% will have triple negative cancers. While there are many similarities, they are distinct entities and BRCA1 and BRCA2 cancers may not respond to treatment in the same way.
Currently there are no approved treatments specifically for BRCA mutated breast cancer patients and these patients are treated according to their hormone receptor and HER2 status.
Olaparib is a potent PARP inhibitor (PARP-1, -2 and -3) that is being developed as an oral therapy, both as a monotherapy (including maintenance) and for combination with chemotherapy and other anti-cancer agents.
The mechanism of action for olaparib results from the trapping of inactive PARP on to the single-strand breaks preventing their repair. Persistence of single strand breaks during DNA replication results in their conversion into the more serious DNA double strand breaks that would normally be repaired by homologous recombination repair. Olaparib has been shown to inhibit selected tumour cell lines in vitro and in xenograft and primary explant models as well as in genetic BRCA knockout models, either as a stand-alone treatment or in combination with established chemotherapies.
The aim of the MA.36 (OlympiA) study is to assess the efficacy and tolerability of oral olaparib in BRCA1/BRCA2 mutation carriers with breast cancer. The MA.36 (OlympiA) trial is based on the hypothesis that the use of a PARP inhibitor earlier in high risk BRCA mutated cancers, where there are predicted to be fewer resistance mechanisms, can improve outcomes. MA.36 will involve about 1500 patients who have been found to carry BRCA1 or BRCA2 mutation and have been diagnosed HER2 negative breast cancer.
The MA.36 (OlympiA) study is currently active in Argentina, Australia, Austria, Belgium, Canada, China, France, Germany, Hungary, Iceland, Israel, Italy, Japan, the Netherlands, Poland, Portugal, South Korea, Spain, Sweden, Switzerland, Taiwan, and the UK. As of January 19, 2016, 2805 patients have been screened and 330 patients have been randomized. It is expected that recruitment will continue to accelerate. There are currently 4 sites active in Canada and we anticipate that the remaining 7 sites will be activated by the end of January 2016.
Please note that Canadian Cancer Trials Group centre participation is limited, and several Canadian sites are currently working on their local activation processes. Given these considerations, we ask that every effort be made to evaluate the ability of your centre to make a meaningful contribution to this study. If your centre will not participate directly but you have patients who potentially meet the inclusion criteria for this study, please consider referring them to one of the active Canadian MA.36 sites for BRCA screening and further evaluation of eligibility.
For more information please contact Cathy Davidson, MA.36 Study Coordinator, at 613-533-6430 or firstname.lastname@example.org