A phase I followed by a randomized phase II trial of two cycles carboplatin-olaparib followed by olaparib monotherapy versus capecitabine in BRCA1- or BRCA2-mutated HER2-negative advanced breast cancer as first line treatment (REVIVAL): study protocol for a randomized controlled trial.

ABSTRACT:

Background

Preclinical studies in breast cancer models showed that BRCA1 or BRCA2 deficient cell lines, when compared to BRCA proficient cell lines, are extremely sensitive to PARP1 inhibition. When combining the PARP1 inhibitor olaparib with cisplatin in a BRCA1-mutated breast cancer mouse model, the combination induced a larger response than either of the two compounds alone. Several clinical studies have investigated single agent therapy or combinations of both drugs, but no randomized clinical evidence exists for the superiority of carboplatin-olaparib versus standard of care therapy in patients with BRCA1- or BRCA2--mutated metastatic breast cancer.

Methods/design

This investigator-initiated study contains two parts. Part 1 is a traditional 3 + 3 dose escalation study o

SUBMITTER: Schouten PC 

PROVIDER: S-EPMC4915081 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature