A phase I dose-escalation trial of stereotactic ablative body radiotherapy for non-spine bone and lymph node metastases (DESTROY-trial)

Abstract

Background: In an oligometastatic setting, metastasis-directed treatment could render patients disease free, possibly for a protracted interval. Stereotactic ablative radiotherapy (SABR) is one of the treatment modalities that can be offered to these patients. In addition, the radiobiological qualities of SABR are promising for the use in perceived radioresistant tumours. There is also emerging evidence that SABR can stimulate the immune response, and a specific therapeutic window may exist for the optimal use of radiotherapy as an immune adjuvant. However, when SABR is considered for non-spine bone or lymph node metastases, the optimal fractionation schedule is not yet known.

Methods: The DESTROY-trial is a non-randomized prospective phase I trial determining a regimen of choice for patients with non-spine bone and lymph node metastases. A total of 90 patients will be included in three different treatment regimens. They will be offered stereotactic ablative radiotherapy in 5, 3 or 1 fractions. Dose-limiting toxicity will be recorded as primary endpoint. Acute and late toxicity, local response and local recurrence, and progression-free survival are secondary endpoints. Liquid biopsies will be collected throughout the course of this study from the second fractionation schedule on.

Discussion: Despite its almost universal use in (oligo-)metastatic patients, the level of evidence supporting radical local treatment in general, and stereotactic radiotherapy in particular, is low. This prospective phase I trial will evaluate different SABR regimens for metastases and the differences in immune-stimulatory effects.

Trial registration: The Ethics committee of the GZA Hospitals (B099201732915) approved this study on 05/07/2017. Amendment for translational research was approved on 06/02/2018. Trial registered on Clinicaltrials.gov ( NCT03486431 ) on 03/04/2018 - Retrospectively registered.

Keywords: Lymph node metastases; Non-spine bone metastases; Stereotactic ablative radiotherapy.

Conflict of interest statement

Ethics approval and consent to participate

The trial will be conducted in compliance with the principles of the Declaration of Helsinki (64th WMA General Assembly, Fortaleza, Brazil, October 2013), the principles of good clinical practice and all of the applicable regulatory requirements. The study protocol received approval of the Ethics Committee of the GZA Hospitals, Belgium on 5th July 2017. Any subsequent protocol amendment will be submitted to the Ethics Committee for approval. CTO trial unit will conduct the trial and has ISO 9001 quality certificate since 18th April 2013. Informed consent from patients is mandatory before recruitment.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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