The goal of this clinical trial is to assess Stereotactic Ablative Radiotherapy (SABR) as a method to delay a change in systemic therapy in patients with oligoprogressive ER-positive, HER2-negative advanced breast cancer. The main question it aims to answer is to assess whether the addition of SABR to continuation of first line endocrine therapy and CDK 4/6 inhibitor (Arm A) to patients with oligoprogressive ER-positive, HER2-negative advanced breast cancer could have longer time to strategy failure (TSF) in comparison to physician choice of systemic treatment (Arm B) in patients who had progressed first line. The treatment strategy in Arm A is to maintain patients on current endocrine therapy and CDK 4/6 inhibitor, controlling localised progressing sites of disease with SABR. Treatment strategy in Arm B is to maintain disease control with physician's choice of systemic therapy alone.
AVATAR II is a phase II multicentre open label, randomised trial. Following informed consent, eligible patients with ER-positive, HER2-negative advanced breast cancer receiving an ET (either AI or selective estrogen receptor degrader in combination with a CDK 4/6 inhibitor with newly diagnosed OPD amenable to SABR will be randomised to either: Arm A: SABR to all known sites of OPD with continuation of first line therapy ET and CDK 4/6 inhibitor Arm B: Physician's choice of systemic treatment Patients must have evidence of radiological response to ET and CDK 4/6 inhibitor for a minimum of six months prior to randomisation (defined as either stable disease or partial response). All patients will be followed up for 3 years after the last patient has been randomised.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
74
Stereotactic Ablative Radiotherapy
Physician's choice of systemic therapy does not mandate a change in systemic therapy, however, SABR is not permitted for management in this arm
Primary Outcome Measure
The primary endpoint of this study is to measure the Time to Strategy Failure between Arm A and Arm B. Treatment strategy failure is defined as time from randomisation to progression of disease resulting in a failure of treatment strategy or death by any cause. Progression, as determined by the Investigator, will be defined according to the Response Evaluation Criteria in Solid Tumors, Version 1.1. (RECIST1.1; Appendix 2) (33) The treatment strategy in Arm A is to maintain patients on current ET and CDK 4/6 inhibitor, controlling localised progressing sites of disease with SABR. Treatment strategy in Arm B is to maintain disease control with physician's choice systemic therapy alone.
Time frame: Time from randomisation to progression of disease resulting in a failure of treatment strategy or death by any cause assessed until withdrawal of consent, death, or 3 years after the last patient has been randomised, whichever is earlier.
Secondary Objective 1
To compare PFS; PFS is assessed from randomisation to the date of the first evidence of progression or death by any cause. A patient will be considered to have progressed if there is evidence on progression according to RECIST1.1 or clinical progression
Time frame: Time from randomisation to progression of disease resulting in a failure of treatment strategy or death by any cause assessed until withdrawal of consent, death, or 3 years after the last patient has been randomised, whichever is earlier.
Secondary Objective 2
To compare progression-free survival 2 (PFS-2); PFS-2 is assessed from randomisation to the date of progression on next line of systemic anti-cancer treatment or death by any cause.
Time frame: Time from randomisation to progression of disease resulting in a failure of treatment strategy or death by any cause assessed until withdrawal of consent, death, or 3 years after the last patient has been randomised, whichever is earlier.
Secondary Objective 3
To compare PFS of next line of treatment (2nd PFS); 2nd PFS is assessed from failure of treatment strategy to progression on next line of systemic anti-cancer treatment or date of death by any cause.
Time frame: Time from randomisation to progression of disease resulting in a failure of treatment strategy or death by any cause assessed until withdrawal of consent, death, or 3 years after the last patient has been randomised, whichever is earlier.
Secondary Objective 4
To compare OS; OS is assessed from randomisation to the date of death by any cause.
Time frame: Time from randomisation to progression of disease resulting in a failure of treatment strategy or death by any cause assessed until withdrawal of consent, death, or 3 years after the last patient has been randomised, whichever is earlier.
Secondary Objective 5
To compare treatment related adverse events (TRAEs); TRAEs are adverse events assessed using the Common Terminology for Adverse Events Version 5.0 (CTCAE v5.0) considered possibly, probably, or definitely related to treatment (systemic therapy or SABR)
Time frame: Time from randomisation to progression of disease resulting in a failure of treatment strategy or death by any cause assessed until withdrawal of consent, death, or 3 years after the last patient has been randomised, whichever is earlier.
Secondary Objective 6
To compare the QoL using the FACT-B total score: Area under the curve (AUC) of the FACT-B Total score from baseline to 48 weeks
Time frame: Time from randomisation to progression of disease resulting in a failure of treatment strategy or death by any cause assessed until withdrawal of consent, death, or 3 years after the last patient has been randomised, whichever is earlier.
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