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

NCT06882499 | Not Yet Recruiting DMC

• 1 other identifier: PMC105165 (24/143)
• Study Type: interventional
• Target: 74
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Metastatic Breast Cancer; Breast Cancer, Metastatic

Keywords

ER-positive, HER2-negative; selective estrogen receptor degrader; endocrine therapy; aromatase inhibitor; CDK 4/6 inhibitor; SABR; oligoprogression; oligometastases; oligometastatic; sbrt

Outcome Measures

Primary Outcomes (1)

• Primary Outcome Measure

  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 Outcomes (6)

• Secondary Objective 1

  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

  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 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 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 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.

Study Arms (2)

SABR to all known sites of oligoprogressive disease with continuation of first line therapy

EXPERIMENTAL

SABR to all known sites of oligoprogressive disease with continuation of first line therapy ET + CDK4/6i

Radiation: Stereotactic Ablative Radiotherapy

Physician's choice of systemic treatment

ACTIVE COMPARATOR

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

Interventions

Stereotactic Ablative Radiotherapy RADIATION

Stereotactic Ablative Radiotherapy

SABR to all known sites of oligoprogressive disease with continuation of first line therapy

Physician's choice of systemic treatment OTHER

Physician's choice of systemic therapy does not mandate a change in systemic therapy, however, SABR is not permitted for management in this arm

Physician's choice of systemic treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has signed the AVATAR-II Patient Information and Consent Form (PICF)
• Male or female, ≥ 18 years of age at the time signing consent
• 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
• 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.)
• 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.
• 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.
• For patients with liver or lung metastases, maximum of 3 oligoprogressive lesions in single organ
• All OPD must be amenable to SABR, as per the radiotherapy guidelines in section 11.1 and Appendix 4 and 5
• ECOG performance status 0-2
• Life expectancy ≥ 6 months
• Clinician and patient are willing to continue current line of therapy
• Patient is able to complete QoL questionnaires, and other assessments required as part of the study

You may not qualify if:

• Is pregnant or lactating at the time of randomisation
• 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
• Evidence of leptomeningeal disease
• Evidence of malignant cord compression
• Evidence of lesion within femoral bone requiring surgical fixation
• Patients with risk of bone fracture are not candidate for SABR (Appendix 4 and 5)
• Previous chemotherapy for metastatic disease Note: chemotherapy for primary breast cancer is allowed
• Contraindications to radiotherapy
• Any condition deeming the patient unsuitable to comply with the study
• 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
• Evidence of progression in more than 5 lesions
• Prior SABR delivered for oligoprogressive disease with the intent of delaying a change in systemic therapy.

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead

Related Publications (32)

• Alomran R, White M, Bruce M, Bressel M, Roache S, Karroum L, Hanna GG, Siva S, Goel S, David S. Stereotactic radiotherapy for oligoprogressive ER-positive breast cancer (AVATAR). BMC Cancer. 2021 Mar 23;21(1):303. doi: 10.1186/s12885-021-08042-w.

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MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• A/Prof Steven David

  Peter MacCallum Cancer Centre, Australia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

A/Prof Steven David

CONTACT

+61 3 9928 9801; steven.david@petermac.org

A/Prof Michelle White

CONTACT

+61 3 9928 8111; michelle@mcc.net.au

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2024
• First Posted: March 18, 2025
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2032
• Study Completion (Estimated): June 1, 2032
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share