One Week Versus Three Week in Adjuvant Radiotherapy in Breast Cancer

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:

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.

Conditions

• Breast Cancer Female

Interventions

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.

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.

Sponsors & Collaborators

• Christian Medical College, Vellore, India

  collaborator OTHER

• Sanjay Gandhi Postgraduate Institute of Medical Sciences

  collaborator OTHER_GOV

• Kasturba Medical College

  collaborator OTHER

• Tata Medical Center

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-03-26

Primary Completion

2029-03-26

Completion

2029-03-26

Countries

• India

Study Locations