Status: Treatment Phase & Follow-up

A prospective, open, randomized, phase II study of carboplatin/ olaparib in the pre-operative treatment of patients with triple-negative primary breast cancer which exhibit the features of positive homologous recombination deficiency (HRD) status

Coordinating Investigator: Christian Singer, Vienna
Start of study 11/2019
Sample size: 90 (national)
Sponsor: ABCSG

Description and status:

ABCSG 45 is an open, randomized phase II study, aiming to enroll 90 patients with early triple-negative breast cancer and homologous recombination deficiency (HRD) in their tumor tissue. The patients are randomized 1:1 to either receive neoadjuvant treatment with the PARP inhibitor olaparib, in combination with carboplatin, or a neoadjuvant taxane- / anthracycline-based chemotherapy (TAC) consisting of doxorubicin or epirubicin, docetaxel and cyclophosphamide. The study consists of 2 sub-phases: in dose-finding phase 1, the maximum tolerated olaparib dose was assessed in 20 patients at 6 sites and the identified olaparib dose is then administered in phase 2, with an additional 70 patients at 9 sites. The primary endpoint of ABCSG 45 is the central evaluation of the residual cancer burden (RCB) after surgery following neoadjuvant treatment to compare the efficiency of 6 cycles of olaparib / carboplatin with 6 cycles of TAC. Furthermore, the pathological complete remission (pCR) is assessed and the quality of life outcomes of participants are recorded using EORTC questionnaires. Dose-finding phase 1 was completed with 20 patients by the end of 2020 and the identified optimal olaparib dose was then used in study phase 2, which has been open for recruitment of additional 70 patients from June 2021 to December 2023. The final 90th patient was enrolled on December 13th, 2023 and recruitment closed.

In Q1/2023, an optional substudy was implemented, which gives patients who complete main study treatment the option to continue with adjuvant intake of daily olaparib for one year. This substudy design was based on the promising OlympiA study results published in 2022 (Geyer et al., Ann. Oncol.), which showed an extension of overall survival after one year of adjuvant olaparib treatment. A total of 20 ABCSG 45 patients is eligible to participate in this substudy, which will be ongoing in 2024.

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