Clinical trial NCT04291378: The DBCG Proton Trial: Photon Versus Proton Radiation Therapy for Early Breast Cancer
Official title: The DBCG Proton Trial. Adjuvant Breast Proton Radiation Therapy for Early Breast Cancer Patients: The Skagen Trial 2, a Clinically Controlled Randomised Phase III Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Early Breast Cancer
Radiation Associated Cardiac Failure
Lead sponsor: Danish Breast Cancer Cooperative Group
Sponsor class: OTHER
First posted: 2020-03-02
Enrollment: 1502
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients are randomised between 2 arms with different types of radiation therapy, and patients in both arms have similar follow up
Primary purpose: TREATMENT

Brief summary: The majority of early breast cancer patients are treated with adjuvant radiation therapy (RT) as part of their multimodal therapy. The aim of the RT is to lower the risk of local, regional and distant failure and improve survival. Modern RT is been provided with photon therapy. Now, more proton therapy facilities are opened, including in Denmark. Proton RT may have the potential to cause lower dose to heart and lung during breast RT. This trial will randomise patients between standard photon RT versus experimental proton RT. The primary endpoint is 10 year risk of heart disease.

Detailed description: Adjuvant breast cancer radiation therapy (RT) is standard for all patients operated with breast conservation and for patients diagnosed with large tumours and/or node-positive disease. Around 65% of all breast cancer patients treated with RT have whole breast RT without nodal RT, whilst the remaining 35% are treated with loco-regional RT (target is breast / chest wall and regional nodal volumes). RT leads to fewer local and regional recurrences, a decrease in breast cancer death and improves overall survival. Since 2014, when the DBCG IMN study showed overall survival gain from internal mammary node (IMN) RT, IMN RT has been standard for all high-risk patients in Denmark. IMN RT causes a significant increase in dose to the heart and lung, thus heart and lung sparing RT techniques based on deep inspiration breath hold (DIBH), volumetric arc therapy and tomotherapy are increasingly used to lower dose to heart and lung whilst maintaining dose to breast and nodal targets. These advanced techniques are used in all DBCG departments routinely. Despite using advanced RT techniques, some patients still receive high RT dose to heart and lung.

Proton therapy (PT) has not been widely used nor investigated for adjuvant breast cancer RT, because there are only few proton centres. However, due to the properties of PT it is possible to achieve optimal dose coverage of relevant targets and at the same time ensure low dose to organs at risk compared with photon RT. In an energy-dependent manner, PT will deposit the majority of its dose in tissue depths defined by the Bragg peak. In practice, this translates into i) the ability to deliver the peak energy to target volumes of irregular 3-dimensional shape using pencil-beam scanning technology, ii) a sharp dose fall-off following deposition of energy in the target and iii) reduction of the integral dose to the patient. Within millimeters, the exit dose drops off from 90% to 10%, resulting in the virtual absence of an exit dose. The effectiveness, safety and feasibility of PT has been reported in few small cohort studies with limited follow up, and there is a lack of clinically controlled randomised trials documenting benefit from PT, evaluated either as higher tumour control and/or as fewer morbidities.

This trial tests standard photon RT versus experimental proton RT for selected early breast cancer patients.

Eligibility criteria: Inclusion Criteria:

* Patient operated for early breast cancer with indication for radiation therapy, where standard planning shows a mean heart dose 4 Gy or more and/or a V20 lung of 37% or more.
* Boost (breast, chest wall and nodal), breast reconstruction (any type, except implants with metal), connective tissue disease, post-operative surgical complications, any breast size and seromas are allowed
* Patient with previous non-breast malignancy is accepted if the patient has been without disease minimum 5 years, and the treating oncologist estimates a low risk of recurrence.
* Life expectancy minimum 10 years

Exclusion Criteria:

* previous breast cancer/ductal carcinoma in situ,
* Previous RT to the chest region
* Pregnant or lactating
* Conditions indicating that the patient cannot go through the RT or follow up
* Patients with Pacemaker or defibrillator are excluded until a guideline for handling them has been developed at the DCPT
* Unknown non-tissue implants upstream of the target volume. NB. all such non-tissue, non-metal objects must be delivered to the DCPT for stopping power determination and evaluation at least a week prior to radiation start.
* Metal implants in the radiation area, including metal in implants.

Primary outcomes:
measure: Radiation associated ischaemic and valvular heart disease
timeFrame: 10 years after RT
Secondary outcomes:
measure: Radiation associated second cancer
timeFrame: 10 years after RT
measure: Distant failure
timeFrame: 10 years after RT
measure: Acute radiation associated morbidity
timeFrame: within 6 months after RT
measure: Late radiation associated morbidity
timeFrame: 10 years after RT
measure: Patient reported outcome measures
timeFrame: 10 years after RT
measure: Translational research
timeFrame: 10 years after RT
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: The Danish Breast Cancer Cooperative Group
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Naestved
country: Denmark
facility: Naestved Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Vejle
country: Denmark
facility: Vejle Hospital
Study officials:
affiliation: Danish Breast cancer Cooperation Group (DBCG)
name: Birgitte V Offersen, phd
role: PRINCIPAL_INVESTIGATOR
References: