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 (HYPORT- Adjuvant)
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Breast Cancer Female
- Sponsor
- Tata Medical Center
- Enrollment
- 2100
- Locations
- 1
- Primary Endpoint
- Locoregional Recurrence Rate (LRR)
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
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: Locoregional Recurrence Rate (LRR) (Cumulative proportion of patients with locoregional recurrence) at 5 years
Secondary Objective:
- 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)
Hypothesis:
- 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.
Intervention: 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 over 3 weeks (with SIB of 8 Gy)*
Test Group: 26 Gy in 5 fractions over 1 week (with SIB of 6 Gy).*
* Use of Sequential Boost is allowed in both arms if prespecified by the institution. If used dose is 12 Gy in 4 fractions in 1 week in both arms.
Outcomes and measures:
- LRR : Cumulative proportion of patients with 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed invasive breast cancers
- •Age \> 18 years
- •ECOG performance status : 0 - 3
- •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:
- •All patients after breast conservation surgery or after neoadjuvant chemotherapy
- •Patients after mastectomy if any of the below:
Exclusion Criteria
- •Presence of any one of the following will exclude the patient from participation in the study:
- •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. Concurrent hormonal therapy or targeted therapy using anti-HER2 agents is allowed.
Outcomes
Primary Outcomes
Locoregional Recurrence Rate (LRR)
Time Frame: 5 years
Cumulative proportion of patients with locoregional recurrence
Secondary Outcomes
- Invasive Disease Free Survival ( iDFS )(5 Years)
- Adverse Event ( AE )(5 Years)
- Overall Survival (OS )(5 Years)
- Quality of Life ( QoL )(12 months)