Preoperative Radiation Therapy and Immediate Breast Reconstruction, a Phase 3 Randomized Controlled Trial in the Belgian Population
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 180
- 试验地点
- 6
- 主要终点
- Patient's satisfaction with breasts.
研究概览
简要总结
The goal of this phase III randomized controlled trial (PRADAIIBE) is to assess if preoperative radiation therapy (Preop-RT) combined with immediate breast reconstruction (IBR) can safely improve both aesthetic and quality of life outcomes in breast cancer patients, compared to the standard of care (SoC) therapy consisting of post-mastectomy radiation therapy (PMRT) and delayed/immediate breast reconstruction, in a population of breast cancer patients with an indication of mastectomy and PMRT.
The following hypotheses and outcomes will be assessed at the primary endpoint of 1 year of follow-up:
- Efficacy: Does Preop-RT+IBR lead to a higher BREAST-Q satisfaction with breasts score (primary endpoint), EQ-5D-5L VAS score , EQ-5D-5L Index score, AIS-Total Aesthetic Score, or a shorter treatment duration compared to SoC?
- Safety: Does Preop-RT+IBR lead to an increase in adverse events (general or surgical), a lower rate of pathologic Complete Response (pCR), or worse survival outcomes compared to SoC? [Note: this study was not powered as a non-inferiority trial, all outcomes will be pooled internationally with parallel studies]
Eligible and consenting participants will undergo screening and baseline assessments. They will then be randomised between experimental (Preop-RT+IBR) and control (SoC) groups, in a 1:1 stratified variable block size design. Follow-up will take place at 3 months, 1, 2, 5, and 10 years after the last study treatment. At baseline and during each follow-up visit each participant will complete the Breast Q 'satisfaction with breasts' and EQ-5D-5L scales, photographs will be taken. During follow-up pCR will be assessed if applicable, adverse events will be registered, and oncological follow-up will be recorded.
详细描述
The PRADAIIBE study is a multicentric phase III randomized controlled trial, investigating the effects of radiation therapy timing on breast reconstruction results in breast cancer patients.
This study will recruit adult female breast cancer patients from the Belgian population, who have an indication for mastectomy, Post-Mastectomy Radiation Therapy (PMRT), and also have a wish for breast reconstruction.
After informed consent is signed, patients will be screened, and included in the study if all eligibility criteria are met. If they are not eligible for participation or choose to withdraw after the ICF was signed, they will be registered as a 'screen failure'.
After study inclusion, baseline assessments take place, this includes two questionnaires, one focussed on patient's satisfaction with their own breasts (BREAST-Q v2, BQ-score), the other one focussed on their quality of life perception (EQ-5D-5L VAS-score and Index-score). Next, four photographs of the exposed breast area will be taken. These photographs will later be assessed by an expert panel (AIS-TAS).
Eligible participants are randomized using the central eCRF randomization tool (Castor EDC). Randomisation is stratified on study site and a variable block size will be used. Resulting in random assignment to one of the following treatment arms:
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
盲法说明
This is an open-label study due to the impracticalities and ethical considerations regarding blinding of both radiation therapy and (sham-)surgeries.
The assessment of the photographs by an external expert panel will be blinded.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Screening assessments, including review of all study eligibility criteria must be completed before enrolment and randomisation.
- •Inclusion criteria:
- •In order to be eligible to participate in this study, a participant must meet all of the following criteria:
- •1. Women ≥18 years with histopathologically confirmed breast cancer who:
- •1.a. require SSM/NSM for any reason (e.g. extensive disease)
- •1.b. require postoperative radiation therapy of at least the chest wall
- •c. have a wish for a breast reconstruction
- •An Eastern Cooperative Oncology Group (ECOG) performance status grade ≤ 2
- •Participant is able and willing to provide written informed consent, which includes compliance with and ability to undergo all study procedures, and attend the scheduled follow-up visit(s) per protocol.
排除标准
- •A potential participant who meets any of the following criteria will be excluded from participation in this study:
- •A previous history of breast cancer or irradiation of the chest wall for any other indication, on the other side (ipsilateral). A bilateral SSM/NSM + reconstruction (e.g. in case of a contralateral prophylactic SSM/NSM), or previous contralateral breast cancer disease/treatment, do not fall under this criterium and are thus allowed.
- •Collagen synthesis disease
- •Ongoing pregnancy
- •Actively breastfeeding
- •Smoking at time of inclusion (a history of smoking is allowed but needs to be registered in the eCRF). No interval between smoking cessation and study inclusion is defined, but the reconstructive surgeon needs to be willing to operate the patient using autologous tissue transfer. This generally translates to a smoking cessation of >3months preoperatively.
- •BMI > 35 kg/m2
- •cT4d tumour, metastatic disease or any reason making SSM/NSM not indicated
研究组 & 干预措施
Standard treatment arm (SoC; PostOperative RT)
Treatment in this arm consists of:
- Mastectomy
- Immediate or delayed breast reconstruction.
- Postoperative radiation therapy, according to the SoC as indicated by international guidelines.
[Systemic treatments are not considered as study treatments and will be implemented at the discretion of the treating physician.]
干预措施: Postoperative radiotherapy (Radiation)
Standard treatment arm (SoC; PostOperative RT)
Treatment in this arm consists of:
- Mastectomy
- Immediate or delayed breast reconstruction.
- Postoperative radiation therapy, according to the SoC as indicated by international guidelines.
[Systemic treatments are not considered as study treatments and will be implemented at the discretion of the treating physician.]
干预措施: Immediate or delayed breast reconstruction (Procedure)
Experimental treatment arm (PreOperative RT)
Treatment in this arm consists of:
- Preoperative radiation therapy (Preop-RT). Preop-RT will be administered according to the same parameters and quality standards as PMRT/WBRT, as indicated by international guidelines.
- Mastectomy combined with immediate breast reconstruction, after a 2-6 weeks interval.
[Systemic treatments are not considered as study treatments and will be implemented at the discretion of the treating physician.]
干预措施: Preoperative radiotherapy (Radiation)
Experimental treatment arm (PreOperative RT)
Treatment in this arm consists of:
- Preoperative radiation therapy (Preop-RT). Preop-RT will be administered according to the same parameters and quality standards as PMRT/WBRT, as indicated by international guidelines.
- Mastectomy combined with immediate breast reconstruction, after a 2-6 weeks interval.
[Systemic treatments are not considered as study treatments and will be implemented at the discretion of the treating physician.]
干预措施: Immediate breast reconstruction (Procedure)
结局指标
主要结局
Patient's satisfaction with breasts.
时间窗: Measured at 1 year after last locoregional treatment.
Operationalisation (measurement variable): The satisfaction with breasts outcome variable is operationalised through the "satisfaction with breasts" scale from the BREAST-Q (v2) 'Reconstruction' or 'Breast Conserving Treatment' Module questionnaires (as applicable). The answers from the questionnaire are then transformed into a 'BREAST-Q Score'. The BREAST-Q score can range from 0 to 100. Analysis metric: BREAST-Q score absolute value will be used for analysis. Method of aggregation: The mean, median, standard deviation and IQR will be reported. Time point(s): A baseline assessment is performed during the screening visit. The primary endpoint is assessed at 1 year of follow-up after the last study treatment (LST).
Patient's satisfaction with breasts.
时间窗: Measured at 3 months, 1year, 2 years, 5 years and 10 years after last locoregional treatment. Primary endpoint: 1 year after LST.
Operationalisation (measurement variable): The satisfaction with breasts outcome variable is operationalised through the "satisfaction with breasts" scale from the BREAST-Q (v2) 'Reconstruction', 'Breast Conserving Treatment', or 'Mastectomy' modules (as applicable). The answers from the questionnaire are then transformed into a 'BREAST-Q Score', using the provided conversion scales.(3) The BREAST-Q score can range from 0 to100. Analysis metric: The transformed value of the BREAST-Q score will be used for analysis. Method of aggregation: Mean, SD, median, IQR, and range will be reported. For comparisons and estimands, please refer to the SAP.
次要结局
- Patient's satisfaction with breasts(Measured at 3 months, 2 years, 5 years and 10 years after last locoregional treatment.)
- Patient quality of life (QoL)(Measured at 3 months, 1 year, 2 years, 5 years and 10 years after last locoregional treatment.)
- Breast cosmetic outcome of the treated breast compared to the untreated breast(Measured at 3 months, 1 year, 2 years, 5 years and 10 years after last locoregional treatment.)
- Adverse events(Measured at 3 months, 1 year, 2 years, 5 years and 10 years after last locoregional treatment.)
- Surgical complications(Measured at 3 months, 1 year, 2 years, 5 years and 10 years after last locoregional treatment.)
- Pathological complete response rate(Measured at 3 months after last locoregional treatment.)
- Quality of Life (EQ-5D-5L VAS score)(A baseline assessment is performed during the screening visit, followed by repeated measurements during the IMFU (if applicable), 3M, 1Y, 2Y, 5Y, and 10Y follow-up visits.)
- Quality of Life (Index score)(A baseline assessment is performed during the screening visit, followed by repeated measurements during the IMFU (if applicable), 3M, 1Y, 2Y, 5Y, and 10Y follow-up visits.)
- Breast cosmesis, objective assessment (AIS - TAS)(Photographs are taken during the screening visit, followed by repeated photographs during the IMFU (if applicable), 3M, 1Y, 2Y, 5Y, and 10Y follow-up visits. Expert panel assessment will take place at a later moment.)
- Frequency and severity of adverse events (General AEs)(AEs will be assessed and recorded continuously, with explicit querying during all follow-up visits.)
- Frequency and severity of adverse events (Surgical AEs)(AEs will be assessed and recorded continuously, with explicit querying during all follow-up visits.)
- Treatment duration(These outcome variables will be continuously recorded as the participant progresses through the study and the data is entered in the eCRF.)
- Pathological complete response rate (pCR)(This outcome variable will be assessed after the pathology report of the removed breast tissues is available. This is checked intermittently during the treatment phase, or at least during the 3 months follow-up visit.)