The EMBRACE trial and AUTO-CHECK study were developed and submitted with support from GCCTI.
EMBRACE is a phase 2 clinical trial of the poly adenosine diphosphate-ribose polymerase (PARP) inhibitor, olaparib, in homologous recombinant- (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 BRCA2, germline or somatic inactivating mutations in other genes involved in repairing HR 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 BRCA1 or BRCA2.
This trial was funded in December 2016 by Cancer Australia and is led by Dr Katrin Sjoquist with support from ANZGOG and BCT.
The study is an open-label, single-arm, signal-seeking, multi-centre phase 2 clinical trial of two molecularly enriched cohorts:
- Relapsed platinum-sensitive high-grade serous ovarian cancer not yet treated for relapsed disease;
- Triple negative breast cancer.
Both cohorts are treated with olaparib 300 mg twice-daily until disease progression or unacceptable toxicity. The primary aim is to evaluate the activity of olaparib in each molecularly-enriched cohort.
Recruitment to the EMBRACE trial finished on 31 March 2022. A total of 22/60 participants were enrolled from 12 sites across Australia. More than 200 patients were screened during the recruitment period. Preparation for publication of the trial results is underway.
For more information about EMBRACE, please visit the ANZCTR website or contact [email protected].
AUTO-CHECK is a translational research study. It looks at the molecular determinants of autoimmunity and immune adverse events in advanced cancer patients who have been treated with immune checkpoint inhibitors (ICIs).
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 (IRAE) after treatment with ICIs.
Collaboration with CTGs: This study was funded in January 2017 by Cancer Australia and is led by Prof Matthew Cook (CIA) and Dr Sonia Yip.
Trials and tumour types: AUTO-CHECK collected biospecimens from six multi-site investigator-initiated trials across four CTGs (ALTG (now known as TOGA), ANZGOG, ANZUP, and COGNO). These trials span five tumour types: mesothelioma (DREAM); non-small cell lung cancer (NIVORAD, ILLUMINATE), endometrial (PHAEDRA), renal cell (KEYPAD), and glioblastoma (NUTMEG) – each trial using ICIs. Biospecimens were also collected from a single centre cohort (Canberra Hospital).
The study aims include to:
- Investigate baseline characteristics of peripheral blood mononuclear cells (PBMCs; enumeration and molecular) that are predictive of IRAEs
- Characterise changes in PBMCs after treatment with ICI and also after an IRAE
- Identify common and rare genetic variants that segregate with IRAEs
- Investigate associations between IRAEs and tumour response
Participants and samples: AUTO-CHECK includes 257 participants with over 450 real-time blood shipments from 48 sites to the central lab situated in the Australian National University. Approximately 50 participants had blood samples following an IRAE.
Analyses: Serological profiling is complete. Whole genome sequencing has been completed. Immune profiling of PBMCs is ongoing. GWAS analyses are ongoing in 2024.
Publications
Blood samples from AUTO-CHECK participants from the Canberra Hospital cohort (lung cancer and melanoma), were analysed as part of this wider study of CD4+ T cells.
Hao Y, Miraghazadeh B, Chand R, Davies AR, Cardinez C, Kwong K, Downes MB, Sweet RA, Cañete PF, D'Orsogna LJ, Fulcher DA, Choo S, Yip D, Peters G, Yip S, Witney MJ, Nekrasov M, Feng ZP, Tscharke DC, Vinuesa CG, Cook MC. CTLA4 protects against maladaptive cytotoxicity during the differentiation of effector and follicular CD4+ T cells. Cell Mol Immunol. 2023 Jul;20(7):777-793. doi: 10.1038/s41423-023-01027-8. Epub 2023 May 9. PMID: 37161048; PMCID: PMC10166697.
For more information about AUTO-CHECK, please visit the ANZCTR website or contact [email protected].
REZOLV3R is a randomised, double-blind, multicentre, phase 3 trial of palliative intraperitoneal bevacizumab following therapeutic ascitic drainage for recurrent, malignant ascites in patients with chemotherapy-resistant solid tumours.
Symptomatic patients with recurrent malignant ascites suitable for paracentesis and a paracentesis-free interval (PFI) of 28 days or less will be randomised 1:1 to a single dose of intraperitoneal bevacizumab or control, following drainage of symptomatic ascites per usual site practice.
The primary objective is to compare time between first and second on study paracentesis, or death (paracentesis free survival time), with secondary objectives including patient-reported outcomes (symptoms, quality of life and supportive care measures), activity measures (numbers and intervals between subsequent paracenteses), overall survival and health economic evaluations (healthcare resource use, health system costs and cost effectiveness).
REZOLV3R is being conducted by CTC in collaboration with GCCTI, ANZGOG, AGITG and CST.
This trial was funded in 2023 by Cancer Australia in the PdCCRS scheme, with a pilot phase supported through a Program Grant to NHRMC CTC. A/Prof Katrin Sjoquist is leading the trial with Prof Michael Friedlander (co-chair) and Dr Katherine Francis (research fellow).
The protocol received ethics approval in March 2024 and recruitment is planned to open in July 2024. Site selection continues; please contact the study team to discuss interest or for more information via [email protected]