The EMBRACE trial and AUTO-CHECK study were developed and submitted with support from GCCTI.
EMBRACE is a phase II clinical trial of the PARP inhibitor, olaparib, in HR-deficient metastatic breast and relapsed ovarian cancer in patients without germline mutations in BRCA1 and BRCA2.
The aim of this trial is to determine if tumours with somatic inactivating mutations of BRCA1 or BCA2, germline or somatic inactivating mutations in other genes involved in repairing homologous recombination defects (e.g. PALB2, CHEK2, ATM, RAD51), or somatic BRCA1 gene silencing by promoter methylation are similarly susceptible to PARP inhibition as tumours with germline inactivating mutations of BRAC1 or BRAC2.
This concept was re-submitted as a project grant application for consideration by the NHMRC and Cancer Australia’s PdCCRS programs. Cancer Australia awarded funding in December 2016. The trial is across 9 sites with the first site opening at St George Hospital in October 2017. The anticipated recruitment period is for approximately 36 months with the study led by Dr Katrin Sjoquist with support from ANZGOG and BCT.
The study is an open – label, single – arm, signal – seeking, multi – centre phase II clinical trials of two molecularly enriched cohorts:
- A) Relapsed platinum-sensitive HGSOC who have not received prior treatment for relapsed disease;
- B) Triple negative breast cancer.
These cohorts will be administered 300mg of Olaparib orally twice daily until disease progression or unacceptable toxicity, with the primary objective measuring activity of Olaparib in each molecularly enriched cohort.
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Immune checkpoint inhibitors are remarkably active in a variety of cancers. The hypothesis of this study is that a group of patients with a genetic susceptibility to autoimmunity are more likely to develop an immune related adverse event (IRAEs) after treatment with immune checkpoint inhibitors.
The AUTO-CHECK study is a translational research study led by Prof Matthew Cook (CIA) and Dr Sonia Yip (GCCTI project team) received Cancer Australia funding, and commenced in March 2017.
AUTO-CHECK uses data and biospecimens from 5 multi-site investigator-initiated trials across 4 co-operative trials groups (ALTG, ANZGOG, ANZUP and COGNO). These trials span 5 tumour types: mesothelioma (DREAM); NSCLC (NIVORAD, ILLUMINATE), endometrial (PHAEDRA), renal cell (KEYPAD) and glioblastoma (NUTMEG) – each trial using immune checkpoint inhibitors.
The study aims include to:
- Baseline molecular predictors of immune-related adverse events,
- Identify common and rare genetic variants that segregate with IRAEs, and
- Characterise changes in peripheral blood lymphocytes (effector, memory and regulatory subsets), and the kinetics and distribution of CTLA4 and PD-1 expression in patients with or without IRAEs.
Blood is shipped in real-time from all participating hospital sites to the ANU where they are processed for peripheral blood mononuclear cells for subsequent analysis. Other whole blood and serum processed and frozen at sites will also be used for AUTO-CHECK.
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