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

BMC Cancer. 2019 Aug 19;19(1):816. doi: 10.1186/s12885-019-5977-6.

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.

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

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Biomarkers, Tumor / blood
  • Dose Fractionation, Radiation
  • Female
  • Follow-Up Studies
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Neoplasms / blood
  • Neoplasms / diagnostic imaging*
  • Neoplasms / radiotherapy*
  • Neoplastic Cells, Circulating / radiation effects*
  • Patient Selection
  • Prognosis
  • Progression-Free Survival
  • Quality of Life
  • Radiosurgery*
  • Surveys and Questionnaires
  • Tomography, X-Ray Computed
  • Tumor Burden

Substances

  • Biomarkers, Tumor

Associated data

  • ClinicalTrials.gov/NCT03721341