Background
Recent data has demonstrated improvements in overall survival in patients with NSCLC treated with nivolumab. Radiation may augment the immune response through abscopal effects - evidence of tumour control at sites other than those irradiated. We hypothesize that the addition of SABR to immunotherapy with nivolumab will improve progression free survival (PFS) compared with nivolumab alone.
Methods:
DESIGN: open label, randomised phase II trial. ELIGIBILITY: metastatic NSCLC progressing after 1 or 2 lines of chemotherapy with an asymptomatic site of metastasis suitable for SABR. STRATIFICATION: age, lines of chemotherapy, histology and treating institution. TREATMENT: A single dose of SABR (18-20Gy) delivered during cycle 1 (Day 8-14) of nivolumab or nivolumab alone (240mg 2-weekly) given until disease progression or prohibitive adverse events. ENDPOINTS: PFS at 6 months (PFS6; primary), objective tumour response rate, adverse events, overall survival, PFS at 1 and 2 years, associations between possible prognostic/predictive biomarkers and outcomes (including PD-L1 expression). STATISTICS: 120 participants allocated in a ratio of 2:1, 80 to nivolumab + SABR and 40 nivolumab alone to provide 80% power, one-sided type I error rate of 5% for PFS6 of 50% (worthy of pursuit) vs 35% (not worthy of pursuit). BIOSPECIMENS: Tumour tissue and serial bloods will be collected for translational research. CURRENT ENROLMENT (as of 3 Aug 2018): 15 sites open across ANZ, 22 patients have been enrolled.
NIVORAD is an investigator-initiated, cooperative-group trial led by the Australasian Lung Cancer Trials Group (ALTG) in collaboration with the NHMRC Clinical Trials Centre, University of Sydney and the Trans Tasman Radiation Oncology Group (TROG).
Australian New Zealand Clinical Trials Registry: ACTRN12616000352404