Abstract OT2-07-11: Ixazomib in combination with carboplatin in pretreated women with advanced triple negative breast cancer, a phase I/II trial (AGMT MBC-10 trial)

Abstract

Abstract Background: Triple-negative breast cancer (TNBC) comprises a heterogeneous group of diseases which are generally associated with a poor prognosis. Up to now, no targeted treatment beyond anti-VEGF therapy is approved for TNBC so far and cytotoxic agents are the mainstay for the treatment of advanced tumor stages. Ixazomib is a selective, and reversible inhibitor of the proteasome, which has been mainly investigated in the treatment of multiple myeloma. In a preclinical study triple-negative breast cancer cells were treated with bortezomib, a first generation proteaseome inhibitor, alone and in combination with cisplatin, which had a synergistic effect. Clinical data are available for carboplatin plus bortezomib in metastatic ovarian and lung cancers showing remarkable antitumor activity and good tolerability. Based on this rational, the MBC-10 trial will evaluate the toxicity profile and efficacy of ixazomib in combination with carboplatin in patients with advanced TNBC. Trial Design: Patients with metastatic TNBC pretreated with at least one prior line of chemotherapy for advanced disease with a confirmed disease progression and measurable disease are eligible for this study. Patients will receive ixazomib in combination with carboplatin on days 1, 8, and 15 in a 28-day cycle. The phase I part of this study uses an alternate dose escalation accelerated titration design. After establishing the maximum tolerated dose (MTD), accrual continues to evaluate the efficacy and safety of the combination (phase II, including 41 evaluable patients). All patients will continue on study drugs until disease progression, unacceptable toxicity or discontinuation for any other reason. Primary endpoint of the phase II is overall response rate, secondary endpoints include safety profile, progression-free survival and quality of life. This trial is open for patient enrollment since November 2016 in six Austrian cancer centers. Accrual is planned to be completed within two years. ClinicalTrials.gov Identifier: NCT02993094 Citation Format: Rinnerthaler G, Gampenrieder SP, Petzer A, Pusch R, Fridrik M, Rossmann D, Balic M, Egle D, Rumpold H, Singer C, Bartsch R, Melchardt T, Ulmer H, Mlineritsch B, Greil R. Ixazomib in combination with carboplatin in pretreated women with advanced triple negative breast cancer, a phase I/II trial (AGMT MBC-10 trial) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT2-07-11.