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
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 74
- 主要终点
- Primary Outcome Measure
研究概览
简要总结
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 treatment failure (TTF) 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.
详细描述
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.
All patients will be followed up for 3 years after the last patient has been randomised.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients will be eligible for inclusion in this trial if all the following criteria apply:
- •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.
- •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, 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 of Protocol v2.3 dated 20Feb2026
- •ECOG performance status 0-2
- •Life expectancy ≥ 6 months
- •Clinician and patient are willing to continue current line of therapy if randomised to Arm A
- •Patient is able to complete QoL questionnaires, and other assessments required as part of the study
排除标准
- •Patients will not be eligible for inclusion in this trial if any of the following criteria apply:
- •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 of Protocol v2.3 dated 20Feb2026)
- •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.
研究组 & 干预措施
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
干预措施: Stereotactic Ablative Radiotherapy (Radiation)
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
干预措施: Physician's choice of systemic treatment (Other)
结局指标
主要结局
Primary Outcome Measure
时间窗: 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.
次要结局
- 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.)
- Secondary Objective 6(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 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.)