Clinical trial NCT06882499: Stereotactic Ablative Body Radiotherapy (SABR) with Maintenance of Systemic Therapy Versus Physicians' Choice of Systemic Therapy for Oligoprogressive ER-positive, Her-2 Negative Breast Cancer II
Official title: Stereotactic Ablative Body Radiotherapy (SABR) with Maintenance of Systemic Therapy Versus Physicians' Choice of Systemic Therapy for Oligoprogressive ER-positive, Her-2 Negative Breast Cancer II
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Breast Cancer, Metastatic
Metastatic Breast Cancer
Keywords: ER-positive, HER2-negative
selective estrogen receptor degrader
endocrine therapy
aromatase inhibitor
CDK 4/6 inhibitor
SABR
oligoprogression
oligometastases
oligometastatic
sbrt
Lead sponsor: Peter MacCallum Cancer Centre, Australia
Sponsor class: OTHER
Collaborators: name: Monash Health
name: Monash Medical Centre
First posted: 2025-03-18
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: INCLUSION CRITERIA

Patients will be eligible for inclusion in this trial if all the following criteria apply:

1. Patient has signed the AVATAR-II Patient Information and Consent Form (PICF)
2. Male or female, ≥ 18 years of age at the time signing consent
3. Patients with histologically proven ER-positive, HER2-negative advanced breast cancer receiving an ET in combination with a CDK 4/6 inhibitor. Biopsy of metastatic disease if technically feasible but not mandatory
4. Patients must have evidence of extracranial metastatic disease, with no evidence of uncontrolled intracranial metastases
5. 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) Note: Patient must have ongoing stability/response in at least one lesion at the time of randomisation.
6. Evidence of new or existing OPD, as determined by the Investigator and defined according to RECIST1.1 (33), via CT on a per-lesion basis (between 1-5 metastases, including the primary) as follows:

   * At least a 20% increase in the diameter of a lesion, taking as reference the smallest diameter on a previous CT scan with an absolute increase of at least 5 mm
   * Appearance of a new lesion(s) Note: A new lesion can be identified using various imaging modalities, such as PET-CT or WBBS, as long as the lesion is visible on serial CT scans.
7. For patients with liver or lung metastases, maximum of 3 oligoprogressive lesions in single organ
8. All OPD must be amenable to SABR, as per the radiotherapy guidelines in section 11.1 and Appendix 4 and 5
9. ECOG performance status 0-2
10. Life expectancy ≥ 6 months
11. Clinician and patient are willing to continue current line of therapy
12. Patient is able to complete QoL questionnaires, and other assessments required as part of the study

EXCLUSION CRITERIA

Patients will not be eligible for inclusion in this trial if any of the following criteria apply:

1. Is pregnant or lactating at the time of randomisation
2. Evidence of more than one clone of metastatic disease e.g., a patient with both ER-positive and triple negative clones of disease And ER-negative and/or HER2-positive disease would be excluded from the study
3. Evidence of leptomeningeal disease
4. Evidence of malignant cord compression
5. Evidence of lesion within femoral bone requiring surgical fixation
6. Patients with risk of bone fracture are not candidate for SABR (Appendix 4 and 5)
7. Previous chemotherapy for metastatic disease Note: chemotherapy for primary breast cancer is allowed
8. Contraindications to radiotherapy
9. Any condition deeming the patient unsuitable to comply with the study
10. Substantial overlap with previously treated area. Reirradiation is permitted with the condition that the combined plan adheres to the specific dose constraints outlined in this protocol. It is advised to use biological effective dose (BED) calculations to correlate previous doses with the tolerance doses documented below

Primary outcomes:
measure: Primary Outcome Measure
timeFrame: 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 outcomes:
measure: Secondary Objective 1
timeFrame: 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.
measure: Secondary Objective 2
timeFrame: 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.
measure: Secondary Objective 3
timeFrame: 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.
measure: Secondary Objective 4
timeFrame: 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.
measure: Secondary Objective 5
timeFrame: 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.
measure: Secondary Objective 6
timeFrame: 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.
Other outcomes:
Locations:
Study officials:
affiliation: Peter MacCallum Cancer Centre, Australia
name: A/Prof Steven David
role: PRINCIPAL_INVESTIGATOR
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