The HeartSpare Plus 1B Trial

The HeartSpare Plus 1B Trial: A Randomised Phase II Trial Comparing the Resource Impact, Acute Toxicity and Feasibility of Different Pan-lymph Node Radiotherapy Techniques for Breast Cancer Patients

This study aims to compare the resource impact, acute toxicity and feasibility of different pan-lymph node radiotherapy techniques. Radiotherapy using wide tangents with the patient in breath hold will be compared against volumetric modulated arc therapy (VMAT) in free breathing in the main trial. A parallel study will asses the accuracy of VMAT treatments using voluntary deep inspiratory breath hold compared to an active breathing controlled breath hold device.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: WT_vDIBH; Radiation: VMAT_FB

Detailed Description

Following publication of results of two large randomised clinical trials, pan-lymph node radiotherapy (pan-LN RT) (including treatment of the internal mammary chain) is set to become standard treatment in patients with lymph-node positive breast cancer. Traditional pan-LN RT techniques deliver high radiation doses to the heart and lungs which can cause long-term side-effects in women many years after their treatment. Modern techniques including breath-holding and volumetric-modulated arc therapy (VMAT) can reduce doses to heart and lungs but the investigators do not yet know which technique(s) are best in terms of resource costs, short to medium-term side-effects, and day to day accuracy. This study will compare the time taken to deliver pan-LN RT using breath-holding versus VMAT and will collect side-effect data up to one year following treatment as well as modelling long-term cardiac risks based on heart doses delivered. The results of the main study will help guide clinicians and departments in selecting the best pan-LN RT techniques for their patients. A parallel study will evaluate the combination of breath-hold and VMAT using a machine-based technique called the active-breathing controlled (ABC) device against a more simple voluntary breath-hold technique were patients simply take a breath in and hold it for up to 20 seconds at a time. These techniques will be compared in terms of their day-to-day accuracy. If the simpler technique proves as accurate as the ABC-technique, this will establish the simpler technique as a less resource-intensive standard of care adoptable by other radiotherapy departments.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 years
• Female or male
• Invasive carcinoma of the breast (left or right-sided)
• Breast conservation surgery or mastectomy
• Axillary staging and/or dissection
• pT1-T4,N1-2,M0 disease
• Histological involvement of axillary lymph nodes
• Indication for radiotherapy to the IMC, axillary levels I-III and/or level IV
• Patient able to tolerate breath hold
• Performance status 0-1

Exclusion Criteria:

• Contralateral and/or previous ipsilateral breast cancer, irrespective of date of diagnosis
• Past medical history of malignancy except (i) basal cell skin carcinoma, (ii) CIN cervix uteri, (iii) non-breast malignancy allowed if treated with curative intent and at least 5 years disease free
• Previous radiotherapy to any region above the diaphragm

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: WT_vDIBH; Wide tangent radiotherapy in voluntary deep inspiratory breath hold	Radiation: WT_vDIBH
Active Comparator: VMAT_FB; Volumetric modulated arc therapy in free breathing.	Radiation: VMAT_FB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Linear Accelerator time	Patient mounting couch to linear accelerator being turned off	3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute toxicity - Skin	CTCAE grading	5 weeks
Acute toxicity - lung (pneumonitis)	CTCAE grading	5 weeks
Acute toxicity - oesophagitis	CTCAE grading	5 weeks
Acute toxicity - fatigue	EORTC QLQ-C30 + FA13	5 weeks
Acute toxicity - quality of life	EORTC QLQ-C30 + BR23	5 weeks
Intermediate toxicity - lung (pneumonitis)	CTCAE pneumonitis assesment	up to 1 year
Intermediate toxicity - fatigue	EORTC QLQ-C30 + FA13	up to 1 year
Intermediate toxicity - quality of life	EORTC QLQ-C30	up to 1 year
Intermediate toxicity - lymphoedema/ shoulder dysfunction	EORTC BR23	up to 1 year
Organ at risk dose - ipsilateral lung	mean dose to the ipsilateral lung (Gy) measured using DVH	Immediate
Organ at risk dose - contralateral lung	mean dose to the contralateral lung (Gy) measured using DVH	Immediate
Organ at risk dose - heart	mean dose to the heart (Gy) measured using DVH	Immediate
Organ at risk dose - contralateral breast	mean dose to the contralateral breast (Gy) measured using DVH	Immediate
Organ at risk dose - thyroid	mean dose to the thyroid (Gy) measured using DVH	Immediate
Organ at risk dose - humeral head	mean dose to the humeral head (Gy) measured using DVH	Immediate
Organ at risk dose - brachial plexus	maximum dose to the brachial plexus (Gy) measured using DVH	Immediate
Organ at risk dose - Left anterior descending coronary artery	maximum dose to the Left anterior descending coronary artery (Gy) measured using DVH	Immediate
Organ at risk dose - oesophagus	maximum dose to the oesophagus (Gy) measured using DVH	Immediate
Time taken to plan and check radiotherapy		Immediate
Inter-fraction reproducibility	Distance - shift from planning CT on CBCT (mm)	3 weeks

Collaborators and Investigators

• Sponsor: Royal Marsden NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2016
• Primary Completion (Actual): January 15, 2019
• Study Completion (Actual): January 15, 2019

Study Registration Dates

• First Submitted: April 26, 2016
• First Submitted That Met QC Criteria: May 12, 2016
• First Posted (Estimate): May 13, 2016

Study Record Updates

• Last Update Posted (Actual): April 19, 2022
• Last Update Submitted That Met QC Criteria: April 12, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: CCR4501

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES