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 (AVATARII)

March 31, 2026 updated by: Peter MacCallum Cancer Centre, Australia

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

74

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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. (Controlled intracranial metastases are defined as stable disease on repeat CT imaging performed at least one month apart.)

  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 5mm
    • 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 in the protocol
  11. Evidence of progression in more than 5 lesions
  12. Prior SABR delivered for oligoprogressive disease with the intent of delaying a change in systemic therapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SABR to all known sites of oligoprogressive disease with continuation of first line therapy
SABR to all known sites of oligoprogressive disease with continuation of first line therapy ET + CDK4/6i
Radiation: Stereotactic Ablative Radiotherapy
Stereotactic Ablative Radiotherapy
Active Comparator: Physician's choice of systemic treatment
Physician's choice of systemic treatment does not mandate a change in systemic therapy, however, SABR is not permitted for management in this arm
Other: Physician's choice of systemic treatment
Physician's choice of systemic therapy does not mandate a change in systemic therapy, however, SABR is not permitted for management in this arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary Outcome Measure
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.

The primary endpoint of this study is to measure the time to treatment failure between Arm A and Arm B.

Treatment failure is defined as time from randomisation to progression of disease resulting in a failure of treatment strategy or death by any cause.

Progression, will be determined by the Investigator, using the Response Evaluation Criteria in Solid Tumors, Version 1.1. (RECIST1.1; Appendix 2) (33) as a guide.

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 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Secondary Objective 2
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.
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 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
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.
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 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
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.
To compare OS; OS is assessed from randomisation to the date of death by any cause.
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
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.
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 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
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.
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 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
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.
To compare PFS; PFS is assessed from randomisation to the date of the first evidence of progression or death by any cause. Progression will be assessed by the treating clinician as part of standard-of-care practice, using RECIST 1.1 as a guide or based on clinical progression.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peter MacCallum Cancer Centre, Australia

Collaborators

Monash Medical Centre
Monash Health

Investigators

  • Principal Investigator: A/Prof Steven David, Peter MacCallum Cancer Centre, Australia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

June 1, 2032

Study Completion (Estimated)

June 1, 2032

Study Registration Dates

First Submitted

December 8, 2024

First Submitted That Met QC Criteria

March 12, 2025

First Posted (Actual)

March 18, 2025

Study Record Updates

Last Update Posted (Actual)

April 2, 2026

Last Update Submitted That Met QC Criteria

March 31, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PMC105165 (24/143)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Not contractually obliged but it may be considered

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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