Stereotactic ablative radiotherapy for the comprehensive treatment of 4–10 oligometastatic tumors (SABR-COMET-10): study protocol for a randomized phase III trial

Abstract

Background Stereotactic ablative radiotherapy (SABR) has emerged as a new treatment option for patients with oligometastatic disease. SABR delivers precise, high-dose, hypofractionated radiotherapy, and achieves excellent rates of local control for primary tumors or metastases. A recent randomized phase II trial evaluated 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 benefits in progression-free survival and overall survival. The goal of this phase III trial is to assess the impact of SABR in patients with 4–10 metastatic cancer lesions. Methods One hundred and fifty-nine patients will be randomized in a 1:2 ratio between the control arm (consisting of standard of care palliative-intent treatments), and the SABR arm (consisting of standard of care treatment + SABR to all sites of known disease). Randomization will be stratified by two factors: histology (Group 1: prostate, breast, or renal; Group 2: all others), and type of pre-specified systemic therapy (Group 1: immunotherapy/targeted; Group 2: cytotoxic; Group 3: observation). SABR is to be completed within 2 weeks, allowing for rapid initiation of systemic therapy. Recommended SABR doses are 20 Gy in 1 fraction, 30 Gy in 3 fractions, or 35 Gy in 5 fractions, chosen to minimize risks of toxicity. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, time to development of new metastatic lesions, quality of life, 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 clinical outcomes and quality of life, to determine if long-term survival can be achieved for selected patients with 4–10 oligometastatic lesions. Trial registration Clinicaltrials.gov identifier: NCT03721341 . Date of registration: October 26, 2018. Electronic supplementary material The online version of this article (10.1186/s12885-019-5977-6) contains supplementary material, which is available to authorized users.

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

“…See Appendix 1 for World Health Organization Trial Registration Dataset. The methods of this trial are similar to the sister trial SABR-COMET-10, as published elsewhere [6].…”

“…Each participating centre that was not involved in the original SABR-COMET study will be required to send to one of the Principal Investigators a mock treatment plan for the anatomic sites that will be treated (e.g. lung, brain, liver, adrenal), as outlined in the sister SABR-COMET-10 protocol [6].…”

“…The rational for the translational component is outlined in detail in the SABR-COMET-10 trial protocol published in this journal previously [6], which we will not reiterate here, and is summarized in Fig. 2.…”

“…It is plausible that these reported long term survival estimates are mostly a result of selection bias [4,5]. However, emerging phase II trials now provide some supporting evidence of an oligometastatic state, though phase III trial data is lacking, which has been outlined in the SABR-COMET-10 trial protocol published previously in this journal [6].…”

Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial

“…Efforts to develop biomarkers that are prognostic and predictive are underway as part of ongoing clinical trials; for example, SABR-COMET-3 and SABR-COMET-10 are both collecting samples to assess for circulating biomarkers, including circulating tumor DNA and circulating tumor cells. 24 The possible toxicities of SABR must be borne in mind for patients and physicians considering treatment. SABR was well-tolerated in the majority of patients, with a rate of grade ≥ 2 toxicity of only 29%.…”