EASE (brEAst Stereo Elderly): A Phase Ia/Ib Study of Stereotactic Ablative Irradiation as an Alternative to Surgery in Elderly and Comorbid Breast Cancer Subjects
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
Stereotactic body radiotherapy (SBRT) is a modern radiotherapy technique, through which extremely high doses of irradiation are delivered in a very precise manner, within a few fractions. SBRT is increasingly used into clinical practice because it can provide excellent local control, comparable to surgery, in many tumor locations, such as lung, liver or bone. Efforts to develop it for BC treatment are promising, as it is safe, convenient, and effective. To date, SBRT for BC has been developed as an alternative method of partial-breast irradiation (PBI) in the pre- or post-operative setting. Therefore, the doses tested are comparable to the conventional doses used with surgery although its potential as sole local treatment for BC remains unknown. Higher SBRT doses are expected to permit obtaining an ablative effect on tumor and be suitable as an alternative to surgery, but this hypothesis has yet to be tested.
The aim of the present study is to prove the feasibility of SBRT as an ablative treatment in early breast cancer (BC). The primary objective is to find the maximum tolerated dose of SBRT that can be safely administered in inoperable patients with BC, the majority of whom are elderly or oldest old.
The overall objective is to determine whether high precision, dose- and fractionation- adapted SBRT is feasible and safe in inoperable patients with BC. The dose and fractionation-adapted SBRT regimen permits to test feasibility in different tumor sizes.
The primary objective of this study is to establish the maximum tolerated dose (MTD) that can be delivered with a single or few (up to 5) fractions of SBRT in inoperable patients with BC.
详细描述
SBRT will be performed using appropriate LINACs (Truebeam®, Varian, Palo Alto, US or Cyberknife®, Accuray, Morges, Switzerland) with a volumetric arc technique (VMAT), or non-coplanal technique, depending on the treating device. The medical devices have a CE certification and will be used in the trial as stated in the CE-marked instructions for use.
The gross tumor volume (GTV), as visualized on computed tomography (CT) within clips/fiducials, when present, with a 1mm (Cyberknife®)- 3mm (TrueBeam®) isotropic margin will be treated with an adaptive fractionation, depending on its total volume within 1,3 or 5 fractions. An elective volume of 2 cm around the GTV (clinical target volume (CTV)), plus a 1mm (Cyberknife®)- 3mm (TrueBeam®) isotropic margin will be treated at constant doses by fractionation cohort. These planning target volumes (PTVs) will be cropped at 5mm to skin and chest wall. The principle of irradiating an "elective volume" around the GTV will be used in this study, as done by Vasmel et al. [3]. This is decided because uncertainties do exist concerning true micro- and macrometastatic extension around the tumor, as visualized in the CT and delineation of the tumor on injected CT scans is not expected to be sufficient for coverage of macro and micrometastatic disease. Breast MRI is concordant to tumor size, as evaluated in pathology, within 0.5 cm for 53% of patients [4]. Organs at risk will be defined according to international guidelines [5].
Enrolment will be performed within 1-8 weeks after discussion in the HUG Breast Cancer Multidisciplinary Tumor Board (MTB).
All patients diagnosed with BC in our Institution, presenting the aforementioned characteristics, are candidates for screening for participation in the study, and will be offered clip placement, when feasible, during diagnostic biopsy by the specialized radiologist. Screening criteria will be assessed by the radiologist and radiation oncologist at the time of diagnostic biopsy.
Pre-screened patients will be discussed at the Institutional BC MTB. Eligible patients will be considered for the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 70 Years 至 —（Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age over 70 years
- •Histologically confirmed diagnosis of BC, any time before study enrollment.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Patient considered inoperable in multidisciplinary board decision or refusing surgery. Main criteria determining inoperability are inability to receive general anesthesia after anesthetics and/or surgical evaluation. Criteria described in the statement of American Society of Anesthesiologists (ASA) {, #4699} and American College of Surgeons Surgical risk calculators {, #4695} are usually addressed in the multidisciplinary discussion (Appendix ).
- •Presence of measurable disease in the breast, defined as a lesion that can be accurately measured in at least one dimension with imaging (ultrasound, CT or MRI). Disease in the axilla or internal mammary chain is allowed and will be treated at the discretion of the radiation oncologist. Regional disease is not considered in measurements of local response.
- •Primary tumor accessible to SBRT, as defined by treating radiation oncologist.
- •Neo-adjuvant systemic therapy is allowed.
- •Tumor size in planning computed tomography (CT) permitting SBRT delivery. SBRT appropriateness is defined by the treating radiation oncologist.
- •Multifocality (over two tumor foci within the same breast quadrant) is allowed, as long as the total treatment volumes remain suitable for SBRT, as defined by the treating radiation oncologist.
- •Total tumor treatment volume/ whole breast volume ratio not exceeding 30%.
- •Previous treatment for BC to the contralateral breast is allowed. Previous treatment to the same breast for other reason than BC is allowed.
- •Capacity of patient to collaborate for SBRT delivery.
- •Capacity of patient to understand and sign a written informed consent according to International Council for Harmonization (ICH)/Good Clinical Practice (GCP) regulations before registration.
排除标准
- •Prior surgery for the current diagnosis.
- •Prior whole or partial breast irradiation to the involved breast.
- •Absolute contraindication to RT, such as Li-Fraumeni syndrome.
- •Current participation and receipt of study therapy or previous participation in a study of an investigational agent and receipt of study therapy or used an investigation device within 4 weeks of the first day of treatment.
- •Not able to communicate meaningfully with investigator and site staff and/or incapable of discernment.
- •Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.
研究组 & 干预措施
1 fraction SBRT
Treated volume up to 40 cc. Dose escalation from 21 Gy to 23 Gy to 25 Gy every 3 patients if no dose-limiting toxicity (DLT).
干预措施: SBRT (Radiation)
3 fractions SBRT
Treated volume up to 60 cc. Dose escalation from 11Gy/fraction to 13Gy/fraction to 14Gy/fraction every 3 patients if no dose-limiting toxicity (DLT).
干预措施: SBRT (Radiation)
5 fractions SBRT
Treated volume up to 110 cc. Dose escalation from 8Gy/fraction to 9Gy/fraction to 10Gy/fraction every 3 patients if no dose-limiting toxicity (DLT).
干预措施: SBRT (Radiation)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: 4 weeks
Dose before the dose-level at which one or more dose-limiting toxicity (DLT) (any treatment-related toxicity equal or superior to Grade 3, according to CTCAE v5) occurs within 4 weeks after end of study treatment (EOT).
次要结局
- Explorative: clinically relevant technical parameters of SBRT(2 years)
- Quality of life (QoL) before and after SBRT(2 years)
- Differential safety profile between arms(2 years)
- Efficacy o SBRT on local control(2 years)
- Early and late toxicities(2 years)
- Explorative: Time to local, regional and distant progression(2 years)
- Explorative: Association between QoL and SBRT arm(2 years)
研究者
Pelagia Tsoutsou
Head of Radiation Oncology Department
University Hospital, Geneva