One Week Versus Three Week in Adjuvant Radiotherapy in Breast Cancer (HYPORTAdjuvant)

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)

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:

1. Overall survival (OS) (Time from randomization to death)
2. Invasive Disease-free survival (iDFS) (Time from randomization to any invasive disease recurrence, death due to any cause or second invasive malignancy)
3. Late adverse events (AE)
4. Quality of Life (QoL)

Hypothesis:

1. 1 week schedule will be non-inferior to a three week schedule for Locoregional Recurrence Rate
2. 1 week schedule will be non-inferior to a three week schedule for OS
3. 1 week schedule will be not result in worse late adverse events as compared to 3 week schedule
4. 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:

1. LRR : Cumulative proportion of patients with ipsilateral Locoregional Recurrence after treatment at 5 years .
2. OS: Time from randomization to the time of death due to any cause. Cumulative proportion reported at 5 years.
3. iDFS: Time from randomization to any disease recurrence, death due to any cause or second primary invasive cancer.Cumulative proportion reported at 5 years.
4. AE: Proportion of patients with late Grade 2 or more AE as defined by the CTCAE 5 criteria
5. 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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer Female
• Intervention / Treatment: Radiation: 3 week RT; Radiation: 1 week RT

• Study Type: Interventional
• Enrollment (Estimated): 2100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sanjoy Chatterjee, FRCR; Phone Number: 7403 9038161825; Email: sanjoy.chatterjee@tmckolkata.com

Study Locations

• India
  • West Bengal
    • Kolkata, West Bengal, India, 700160
      • Recruiting
      • Sanjoy Chatterjee
      • Contact: Sanjoy Chatterjee, FRCR; Phone Number: 7403 9038161825; Email: chatterjee72@hotmail.com
      • Principal Investigator: Santam Chakraborty, MD
      • Sub-Investigator: Sandip Ganguly, MD
      • Sub-Investigator: Debdeep Dey, FRCPath
      • Sub-Investigator: Anurupa Mahata, MSC Physics
      • Sub-Investigator: Abha Kumari, DNB
      • Principal Investigator: Selvamani Bakianathan, MD
      • Sub-Investigator: Patricia Solomon, MD
      • Sub-Investigator: Rajesh Balakrishnan, MD
      • Principal Investigator: Punita Lal, MD
      • Sub-Investigator: Shagun Misra, MD
      • Sub-Investigator: KJ Maria Das, Phd
      • Contact: Sanjoy Chatterjee, FRCR; Phone Number: 7403 9038161825; Email: sanjoy.chatterjee@tmckolkata.com
      • Sub-Investigator: Rosina Ahmed, FRCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

  • T3 - T4 tumors
  • more than 3 axillary lymph nodes
  • T0-T2 tumor with 0 - 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.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 3 week RT; Adjuvant Radiotherapy delivered over 3 weeks	Radiation: 3 week RT; 40 Gy in 15 fractions over 3 weeks to the whole breast or chest wall. Patients undergoing breast conservation therapy will receive additional boost radiotherapy to the tumor bed. The supraclavicular fossa will be treated in patient with node positive disease or those receiving neoadjuvant chemotherapy. IMC and Axillary radiotherapy will be given as per the institutional policy. Boost Dose schedule for BCS patients will be 8 Gy delivered in 15 fractions simultaneously with tangential EBRT. In institutions planning for sequential boost, a dose of 12 Gy in 4 fractions will be delivered after whole breast EBRT.
Experimental: 1 Week RT; Adjuvant Radiotherapy delivered over 1 week	Radiation: 1 week RT; 26 Gy in 5 fractions over 1 week to the whole breast or chest wall. Treatment volumes will be same as the control arm. Additional boost will be delivered to patients who have undergone breast conservation. Boost Dose schedule for BCS patients will be 6 Gy delivered in 5 fractions simultaneously with tangential EBRT. In institutions planning for sequential boost, a dose of 12 Gy in 4 fractions will be delivered after whole breast EBRT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Locoregional Recurrence Rate (LRR)	Cumulative proportion of patients with locoregional recurrence	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS )	Time from randomization to the time of death due to any cause. Cumulative proportion reported at 5 years	5 Years
Invasive Disease Free Survival ( iDFS )	Time from randomization to any disease recurrence, death due to any cause or second primary invasive cancer. Cumulative proportion reported at 5 years.	5 Years
Adverse Event ( AE )	Proportion of patients with late Grade 2 or more AE as defined by the CTCAE 5 criteria	5 Years
Quality of Life ( QoL )	Proportion of patients with a worse summary score in the health related quality of life as measured using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ C30) at 12 months post-treatment as compared to the baseline score. The total summary score may range between 0 - 100 with higher scores indicating better health related quality of life. This score is the mean of the 13 of the 15 items of the EORTC QLQ C30 questionnaire which include the scores related to all the domains excepting the Global quality of life scale and Financial impact scale.	12 months

Collaborators and Investigators

• Sponsor: Tata Medical Center
• Collaborators: Sanjay Gandhi Postgraduate Institute of Medical Sciences; Christian Medical College, Vellore, India; Kasturba Medical College

Publications and helpful links

General Publications

• Chakraborty S, Chatterjee S; Hyport Adjuvant Author Group. HYPORT adjuvant acute toxicity and patient dosimetry quality assurance results - Interim analysis. Radiother Oncol. 2022 Sep;174:59-68. doi: 10.1016/j.radonc.2022.07.003. Epub 2022 Jul 9.
• Chatterjee S, Chakraborty S; HYPORT Adjuvant Author Group. Hypofractionated radiation therapy comparing a standard radiotherapy schedule (over 3 weeks) with a novel 1-week schedule in adjuvant breast cancer: an open-label randomized controlled study (HYPORT-Adjuvant)-study protocol for a multicentre, randomized phase III trial. Trials. 2020 Sep 30;21(1):819. doi: 10.1186/s13063-020-04751-y.

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2019
• Primary Completion (Estimated): March 26, 2029
• Study Completion (Estimated): March 26, 2029

Study Registration Dates

• First Submitted: December 26, 2018
• First Submitted That Met QC Criteria: December 26, 2018
• First Posted (Actual): December 27, 2018

Study Record Updates

• Last Update Posted (Actual): October 23, 2024
• Last Update Submitted That Met QC Criteria: October 21, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Breast Cancer; Simultaneous integrated boost; Hypo-fractionated Radiotherapy,; One week Radiotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 2018/TMC/133/IRB/31

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No