Axillary Radiotherapy or Axillary Lymph Node Dissection in Patients With Clinically Node- Positive Breast Cancer Undergoing Upfront Tailored Axillary Surgery: An International, Randomized Superiority Trial (OPBC-10/ NOAX)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 1,060
- 试验地点
- 54
- 主要终点
- Change in arm-related Quality of Life (QoL)
研究概览
简要总结
This trial is to investigate if in patients with clinically node positive breast cancer undergoing upfront surgery, treatment with TAS and ART is superior to ALND in terms of arm-related Quality of Life (QoL) and occurrence of lymphedema two years after randomization.
详细描述
Despite major morbidity, axillary lymph node dissection (ALND) is standard of care in patients with clinically node positive breast cancer (cN+ BC) who undergo upfront surgery, which is frequently indicated in case of luminal biology. Tailored axillary surgery (TAS) was shown to selectively target positive nodes, thereby removing significantly more nodes than sentinel lymph node biopsy (SLNB), but less nodes than ALND. Therefore, it is currently unclear if TAS in combination with axillary radiotherapy (ART) exposes the axilla to less harm compared to ALND. It is hypothesized that patient's quality of life (QoL) and morbidity can be improved by replacing ALND with the combination of TAS and ART in patients undergoing upfront surgery.
The main goal of this trial is to investigate if in patients with clinically node positive breast cancer undergoing upfront surgery, treatment with TAS and ART is superior to ALND in terms of arm-related QoL and occurrence of lymphedema two years after randomization.
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 (Investigator)
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
- •at screening:
- •Written informed consent according to ICH/GCP regulations prior to any trial specific procedures.
- •Patients ≥ 18 years of age.
- •Node-positive breast cancer (histologically or cytologically proven both in primary tumor and in lymph node) American Joint Committee on Cancer/ International Union Against Cancer (AJCC/UICC) stage II-III (all molecular subtypes allowed).
- •Node-positivity detected by imaging and non-palpable (iN+) and confirmed by pathology.
- •Node-positivity palpable (cN1-3) and confirmed by pathology.
- •Occult breast cancer is allowed, if biopsy-proven axillary lymphatic metastasis is present.
- •Eligible for primary ALND or SLN procedure and either:
- •Newly diagnosed.
- •Isolated in-breast recurrence or second ipsilateral breast cancer after previous breast conserving surgery and sentinel procedure and at least 3 years disease free and no prior axillary dissection or axillary RT.
- •Upfront surgery setting.
- •Most suspicious axillary lymph node clipped. (If clipping is not part of the routine, this should be done after consent of the patient as a study procedure.)
- •Ability to complete the QoL questionnaires.
- •WHO performance status 0-2
- •Adequate condition for general anesthesia, breast cancer surgery and radiotherapy.
- •Adult patients (≥18 years of age).
- •Women of child-bearing potential are using effective contraception (condom, diaphragm, intrauterine device), are not pregnant or lactating and agree not to become pregnant during trial treatment (until end of RT) and thereafter during the time recommended by the guidelines - also for adjuvant systemic therapies. A negative pregnancy test before registration is required for all women of child-bearing potential.
- •Men agree not to father a child during trial treatment and for 6 months afterward.
排除标准
- •at screening:
- •Stage IV breast cancer.
- •Clinical N3c breast cancer without axillary disease (clinical N3a and clinical N3b are allowed).
- •Clinical N2b breast cancer (clinical N2a is allowed).
- •Contralateral breast cancer within 3 years.
- •Prior axillary surgery (except prior sentinel node procedure in case of in-breast recurrence).
- •Prior regional radiotherapy.
- •Neoadjuvant treatment with the exception of bridging therapy given for less than 3 months.
- •History of hematologic or primary solid tumor malignancy, unless in remission for at least 3 years from pre-registration with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer.
- •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.
- •Exclusion criteria at randomization (intraoperatively):
- •Absence of clip in the specimen radiography.
- •Palpable disease left behind in the axilla after TAS.
- •No SLN identified in the axilla.
研究组 & 干预措施
Arm A (Control): ALND
- Surgery: Tailored Axillary Surgery (TAS) includes the sentinel lymph node (SLN) procedure, radiographic confirmation of the removal of previously marked lymph nodes (clip removal), and the targeted excision of palpably suspicious lymph nodes.
- Surgery: ALND - current standard of care, with the intention to remove the entire soft tissue within the anatomical borders of the axilla.
- Radiotherapy: All patients receive adjuvant breast irradiation following breast-conserving surgery, along with extended regional lymph node irradiation (breast/chest wall irradiation excluding the axilla).
干预措施: Axillary lymph node dissection (ALND) (Procedure)
Arm B (Investigational): ART
- Surgery: Tailored Axillary Surgery (TAS) includes the sentinel lymph node (SLN) procedure, radiographic confirmation of the removal of previously marked lymph nodes (clip removal), and the targeted excision of palpably suspicious lymph nodes.
- Radiotherapy: All patients receive adjuvant breast irradiation following breast-conserving surgery, along with extended regional lymph node irradiation (breast/chest wall irradiation excluding the axilla).TAS + breast/chest wall and axillary irradiation (ART)
- Radiotherapy: Axillary radiotherapy (ART).
干预措施: Axillary radiotherapy (ART) (Procedure)
结局指标
主要结局
Change in arm-related Quality of Life (QoL)
时间窗: From baseline to 2 years after randomization
The arm subscale (ARM) of the FACT-B+4 is used to assess arm-related QoL.The FACT-B comprises five subscales: physical well-being (seven items), social well-being (seven items), emotional well-being (six items), functional well-being (seven items), and concerns specific to patients with breast cancer (13 items). The FACT-B+4 questionnaire consists of the FACT-B subscales and the additional ARM subscale including five questions related to arm morbidity with four additional validated arm morbidity items that are added to the one item on arm morbidity already included in the FACT-B questionnaire. Patients are asked to indicate on a five- point scale from 0 (not at all), 1 (a little bit), 2 (somewhat), 3 (quite a bit), to 4 (very much), to what degree each statement applied over the previous 7 days. The individual scoring of each question is inverted and added up to the total score ranging between 0 and 20 points, higher scores representing less arm problems.
Occurrence of lymphedema
时间窗: From baseline to 2 years after randomization
Bilateral measurements will be obtained 10 cm above and 5 cm below the olecranon process on both the ipsilateral and contralateral upper extremities. The change in ipsilateral upper- extremity circumference, corrected for any change in the contralateral upper extremity, will be calculated using the following formula: L = (Ia - Ib) - (Ca- Cb). It indicates ipsilateral upper-extremity circumference, C indicates contralateral upper- extremity circumference, a indicates assessments during trial treatment and follow-up, and b indicates baseline assessment. L will be calculated for both upper arm and forearm, and lymphedema is defined as present if L \> 2 cm for either location. The proportion of patients with lymphedema will be calculated.
次要结局
未报告次要终点