Stereotactic ablative radiotherapy for the comprehensive treatment of 1-3 Oligometastatic tumors (SABR-COMET-3): study protocol for a randomized phase III trial

Abstract

Background: A recent randomized phase II trial evaluated stereotactic ablative radiotherapy (SABR) in a group of patients with a small burden of oligometastatic disease (mostly with 1-3 metastatic lesions), and found that SABR was associated with a significant improvement in progression-free survival and a trend to an overall survival benefit, supporting progression to phase III randomized trials.

Methods: Two hundred and ninety-seven patients will be randomized in a 1:2 ratio between the control arm (consisting of standard of care [SOC] palliative-intent treatments), and the SABR arm (consisting of SOC treatment + SABR to all sites of known disease). Randomization will be stratified by two factors: histology (prostate, breast, or renal vs. all others), and disease-free interval (defined as time from diagnosis of primary tumor until first detection of the metastases being treated on this trial; divided as ≤2 vs. > 2 years). The primary endpoint is overall survival, and secondary endpoints include progression-free survival, cost effectiveness, time to development of new metastatic lesions, quality of life (QoL), and toxicity. Translational endpoints include assessment of circulating tumor cells, cell-free DNA, and tumor tissue as prognostic and predictive markers, including assessment of immunological predictors of response and long-term survival.

Discussion: This study will provide an assessment of the impact of SABR on survival, QoL, and cost effectiveness to determine if long-term survival can be achieved for selected patients with 1-3 oligometastatic lesions.

Trial registration: Clinicaltrials.gov identifier: NCT03862911. Date of registration: March 5, 2019.

Keywords: Cancer; Oligometastases; Quality of life; Stereotactic radiotherapy; Survival.

Conflict of interest statement

None to declare from the study sponsor, Principle Investigators, any study investigators, or any translation scientists.

Figures

Fig. 1

Study Schema. SABR = stereotactic ablative radiotherapy; W = weeks; M = months. *histology dichotomized as prostrate, breast, or renal vs. all others. **disease free interval defined as time from diagnosis of primary tumor until first detection of metastatses, and dichotomized as ≤2 vs. > 2 years

Fig. 2

Peripheral Blood Collection Timeline. SOC = standard of care; SABR = stereotactic ablative radiotherapy. Study completion is defined as 5 years of follow-up. Samples will include 2 vials of blood for circulating tumor DNA and peripheral blood mononuclear cell isolation