HYPOfractionated Radiation Therapy comparing a standard radiotherapy schedule (over three weeks) with a novel one week schedule in Adjuvant breast cancer: An open label randomised controlled study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 2,100
- 试验地点
- 5
- 主要终点
- The primary outcome of interest is the cumulative proportion of locoregional recurrence which is defined as any invasive recurrence in the ipsilateral breast or chest wall or ipsilateral axillary, supraclavicular or internal mammary lymph nodes (ipsilateral lymph nodes level 1 - 4 and internal mammary nodes. Note that cutaneous metastatic disease will not be considered as locoregional recurrence unless localized to the ipsilateral breast/chest wall.
研究概览
简要总结
| Background |
Moderate three week hypofractionated adjuvant radiotherapy schedule is a standard care in breast cancers. A five day schedule has been demonstrated to be iso-toxic as a standard three week schedule. Recently studies have also demonstrated the safety and feasibility of simultaneous integrated boost in this setting. This randomized trial will investigate if a one-week course of hypofractionated breast radiotherapy is non-inferior to a three week course.
|Aim
To determine if one-week schedule of adjuvant radiotherapy in breast cancer is non-inferior to a three week schedule.
|Primary objective (endpoint)
Locoregional Recurrence Rate (LRR) (Cumulative incidence of locoregional recurrence) at 5 years
|Secondary objectives (endpoints)
- Overall survival (OS) (Time from randomization to death)
- Invasive Disease-free survival (iDFS) (Time from randomization to any invasive disease recurrence, death due to any cause or second invasive malignancy)
- Late adverse events (AE)
- Quality of Life (QoL)
|Hypotheses
- 1 week schedule will be non-inferior to a three week schedule for Locoregional Recurrence Rate
- 1 week schedule will be non-inferior to a three week schedule for OS
- 1 week schedule will be not result in worse late adverse events as compared to 3 week schedule
- Proportion of patients decrease in quality of life will not differ between the two arms at 12 months
|Design
Open-label, parallel group, two arm, randomised, phase III, non-inferiority trial.
|Population
Patients with breast cancer who need adjuvant radiotherapy after breast conservation or mastectomy.
|Interventions
Patients will be randomized to 15 days or 5 days of radiotherapy to the whole breast or chest wall or reconstructed breast. Nodal radiation will be delivered as indicated. A simultaneous integrated boost (SIB) will be delivered to patients who need a tumor bed boost after breast cancer. The following dose schedules will be tested:
Control Group: 40 Gy in 15 fractions (alongside SIB of 8 Gy)
Test Group: 26 Gy in 5 fractions (alongside SIB of 6 Gy).
|Outcomes and Measures
- LRR : Cumulative incidence of ipsilateral Locoregional Recurrence after treatment at 5 years.
- OS: Time from randomization to the time of death due to any cause. Cumulative proportion reported at 5 years.
- iDFS: Time from randomization to any disease recurrence, death due to any cause or second primary invasive cancer. Cumulative proportion reported at 5 years.
- AE: Proportion of patients with late Grade 2 or more AE as defined by the CTCAE 5 criteria
- QoL: Proportion of patients with a worse summary score in the EORTC QLQ C30 at 12 months post-treatment as compared to the baseline score.
|Assessments
History and Physical Examination before registration, completion of RT, every 6 months for 1st to 5th year.
|Statistical considerations
The sample size is 2100 patients with equal allocation in each group. This provides 80% power with a 1 sided alpha error of 0.025 to exclude a worsening of 3% in the 5-year locoregional recurrence rate while assuming that the rate in the control arm is 95%. Stratification will be done based on the type of surgery (Breast conservation vs Mastectomy), node positivity (Node-positive or Node Negative) and Triple Negative Breast Cancer (TNBC) (yes or no). The total number of events required is 140 and an interim analysis is planned once 16 events would have occurred or at 3 years whichever is earlier.
|Feasibility
Tata Medical Center treats approximately 300 new breast cancer patients annually with adjuvant radiotherapy and about 30% of the patients are referred outside. With the expansion of radiotherapy services approximately 500 new breast cancer patients would be treated at the center annually. It is thus feasible to recruit the required number of patients over a period of 5 years from Tata Medical Center itself. However for a trial of this magnitude we will be expanding the access to the trial to multiple centers and initial talks have been conducted with several national centers.
|Significance
This study will provide level I evidence regarding the safety and efficacy of a 5-day schedule of radiotherapy. This will allow the establishment of a resource sparing schedule of radiotherapy that can result in significant direct and indirect cost savings.
研究设计
- 研究类型
- Interventional
- 分配方式
- Permuted block randomization, variable
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Histologically or cytologically confirmed invasive breast cancers
- •ECOG performance status :
- •Underwent curative intent surgery for the breast cancer with complete microscopic resection either in the form of a mastectomy or breast conservation surgery
- •Adequate axillary clearance or a validated sentinel node biopsy procedure. For the purpose of this study, adequacy of the axillary clearance will be determined by a multidisciplinary tumor board and rationale for the decision documented in the case records. As a general guideline, at least 10 axillary lymph nodes need to be sampled for an axillary nodal dissection to be considered as adequate.
- •Absence of distant metastases. Patients who have high risk breast cancer as defined by a Nottingham Prognostic Index (NPI) of > 5.4 will be considered for metastatic workup in the form of a 18 FDG PET CT. Alternatively, a CT scan of the thorax and whole abdomen, and a bone scan is also allowed. Metastatic workup will also be recommended in patients with AJCC 8 T3/T4 tumors at presentation, 4 or more nodes positive after surgery (pN2 or above). Patients with low or intermediate NPI will be considered for metastatic workup on a case by case basis. Metastatic workup will also be recommended for all patients undergoing neoadjuvant chemotherapy for locally advanced breast cancers.
- •Clear margins of resection for the breast primary as defined by absence tumor on ink in the specimen if a breast conservation has been performed or excision upto the deep fascia of the pectoralis major or skin.
- •Adjuvant radiotherapy is indicated. The following patients will be considered as candidates to receive adjuvant radiotherapy: A. All patients after breast conservation surgery or after neoadjuvant chemotherapy B. Patients after mastectomy if any of the below: i. T
- •T4 tumors ii. > 3 axillary lymph nodes iii. T0-T2 tumor with
- •3 axillary lymph nodes with a Cambridge Score of 3 or more. The SCF will be included in patients with axillary nodal involvement in pathology or in those patients who have undergone neoadjuvant chemotherapy. The internal mammary nodes will be included based on the institutional policy.
排除标准
- •Patients with pure ductal carcinomas in situ (in patients undergoing upfront surgery).
- •Patients with non-epithelial malignant conditions of the breast viz.
- •Sarcomas, lymphomas, phyllodes tumors
- •Patients with metaplastic breast cancers
- •Presence of pathologically proven residual supraclavicular nodal metastases or residual internal mammary lymphadenopathy at time of radiotherapy.
- •Prior radiotherapy to the ipsilateral breast/chest wall or the mediastinum.
- •Patients with synchronous / metachronous contralateral breast malignancies will be eligible for inclusion.
- •Patients requiring bilateral breast radiotherapy are also eligible for inclusion.
- •Concurrent illness, including severe infection that may jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
- •Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.
- •Patients planned for concurrent chemotherapy during radiation therapy.
结局指标
主要结局
The primary outcome of interest is the cumulative proportion of locoregional recurrence which is defined as any invasive recurrence in the ipsilateral breast or chest wall or ipsilateral axillary, supraclavicular or internal mammary lymph nodes (ipsilateral lymph nodes level 1 - 4 and internal mammary nodes. Note that cutaneous metastatic disease will not be considered as locoregional recurrence unless localized to the ipsilateral breast/chest wall.
时间窗: 5 years
次要结局
- Overall Survival: interval of time between the date of randomization to the date of death due to any cause.(5 years)
- Invasive Disease Free Survival: This is defined at the time from randomization to the time any recurrence (pre-invasive / invasive), distant metastases, death from any cause and second invasive primaries, including invasive neoplasms of the breast.(5 years)
- Adverse Events: Acute and Late adverse event rates. Events defined as per the CTCAE 5.0 criteria.(5 years)
- Quality of Life: Proportion of patients in whom the summary score of the EORTC QLQ C30 is equal to or better than the baseline at 12 months in the two arms.