Partial Breast Versus no Irradiation for Women With Early Breast Cancer

The DBCG RT Natural Trial: Partial Breast Versus no Irradiation for Women >=60 Years Operated With Breast Conservation for an Early Breast Cancer: a Clinically Controlled Randomized Phase III Trial

All early breast cancer patients are offered adjuvant breast radiation therapy (RT) after breast conserving surgery for an early breast cancer. Breast cancer is heterogeneous, and selected patients have a very low gain from RT, whilst they still have risk of acute and late side effects from RT. This trial will try identify selection criteria for low risk breast cancer patients who can safely omit adjuvant RT without unacceptable high risk of local failure.

Study Overview

• Status: Recruiting
• Conditions: Pain; Death; Scar; PROMs; Telangiectasia; Local Neoplasm Recurrence; Distantly Metastatic Malignant Neoplasm; Fibrosis Breast; Depigmentation/Hyperpigmentation of Skin
• Intervention / Treatment: Radiation: No partial breast irradiation

Detailed Description

International standard of therapy is to provide adjuvant breast radiation therapy (RT) after breast conserving surgery for an early breast cancer to lower the risk of local and distant failures. However, breast cancer is a heterogeneous disease, and the gain from RT in selected low risk patients is low. RT may cause acute and late side effects, and some of these may be serious to the patient. Therefore, there is a need to tailor RT utilization to the individual recurrence risk and try identify patients who are unlikely to gain much risk reduction from RT, because those patients can then omit RT and thereby avoid late effects and over-treatment. At the present time there is no consensus as to define the selection criteria for patients who may omit RT.

Based on early results from the randomized DBCG RT PBI trial, external beam 40 Gy/15 fr partial breast irradiation (PBI) has been standard in Denmark since April 2016 for selected low risk breast cancer patients. Based on results from the UK IMPORT LOW trial, the 5 yr local recurrence risk using this technique for PBI is 0.5%, whilst 2% for developing a new contralateral breast cancer.

This trial will investigate if PBI can safely be omitted in selected low risk breast cancer patients without causing unacceptable high risk of local failure.

• Study Type: Interventional
• Enrollment (Anticipated): 926
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Birgitte V Offersen, PhD; Phone Number: +45 28838012; Email: bvo@oncology.au.dk

Study Locations

• Chile
  • Santiago de Chile, Chile
    • Recruiting
    • Ponticia Universidad Catolica de Chile
    • Contact: Tomas Merino Lara
• Denmark
  • Aalborg, Denmark
    • Recruiting
    • Aalborg University Hospital
    • Contact: Tamas Lörinz, MD
  • Aarhus, Denmark
    • Recruiting
    • Aarhus University Hospital
  • Copenhagen, Denmark
    • Recruiting
    • Rigshospitalet
  • Herlev, Denmark
    • Recruiting
    • Herlev Hospital
    • Contact: Louise W Matthiessen
  • Naestved, Denmark
    • Recruiting
    • Naestved Hospital
  • Odense, Denmark
    • Recruiting
    • Odense University Hospital
  • Vejle, Denmark
    • Recruiting
    • Vejle Hospital
• Norway
  • Bergen, Norway
    • Recruiting
    • Haukeland HUS
    • Contact: Hans Petter Eikesdal
  • Bodø, Norway
    • Recruiting
    • Nordlandssykehuset
    • Contact: Bård Mannsåker
  • Kristiansand, Norway
    • Recruiting
    • Kristiansand Hospital
    • Contact: Unn-Miriam Kasti
  • Oslo, Norway
    • Recruiting
    • Oslo University Hospital, Radiumhospitalet
    • Contact: Kristin Reinertsen
  • Stavanger, Norway
    • Recruiting
    • Stavanger hospital
    • Contact: Ingvil Mjaaland
  • Tromsø, Norway
    • Recruiting
    • Tromsø University Hospital
    • Contact: Egil Blix Støre
• Sweden
  • Göteborg, Sweden
    • Recruiting
    • Sahlgrenska University Hospital
    • Contact: Dan Lundstedt
  • Lund, Sweden
    • Recruiting
    • Skanes University Hospital
    • Contact: Sara Alkner
  • Uppsala, Sweden
    • Recruiting
    • Uppsala Akademiska sjukhuset
    • Contact: Henrik Lindman

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

Female patient >=60 years

Primary tumour characteristics by conventional histopathology

• unilateral and unifocal non-lobular histology grade 1-2
• maximum microscopic size <=20mm
• node negative determined by sentinel node or axillary lymph node dissection
• estrogen receptor >=10% positive
• HER2 negative (by IHC and/or in situ hybridization)
• resection margin >=2 mm for invasive carcinoma and any ductal carcinoma in situ associated with the cancer

Surgical type is breast conservation

Performance status ECOG 0-2

No evidence of distant metastasis

Exclusion Criteria:

• multifocal or multicentric invasive carcinoma or ductal carcinoma in situ
• evidence of clinical or pathological T4 breast cancer
• grade 3 malignancy
• previous breast cancer or DCIS irrespective of disease-free interval
• previous radiation therapy to the breast or thorax,
• previous neoplasm within 5 years except carcinoma in situ of the cervix, endometrium or coli, melanoma in situ.
• comorbidity precluding the patient from radiation therapy (e.g. cardiovascular or pulmonary disease, scleroderma, systemic lupus erythematosus).
• mental/psychiatric disorder which precludes the patient from understanding the randomization and the follow up.
• documented hereditary breast cancer or with high genetic risk of breast cancer
• life expectancy <10 years

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: Partial breast irradiation; External beam irradiation 40 Gy / 15 fractions, 5 fractions per week, 3 weeks	Radiation: No partial breast irradiation; Omission of radiation therapy
No Intervention: No partial breast irradiation; No radiation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Invasive local recurrence	Invasive local recurrence	10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Regional nodes recurrence	Invasive recurrence in regional nodes of the treated breast	10 years
Distant failure	Invasive recurrence from the breast cancer outside the loco-regional area	10 years
Death	Death and cause of death	10 years

Collaborators and Investigators

• Sponsor: Danish Breast Cancer Cooperative Group
• Collaborators: Danish Cancer Society; Danish Center for Interventional Research in Radiation Oncology (CIRRO)
• Investigators: Principal Investigator: Birgitte V Offersen, PhD, Danish Breast Cancer Group

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2018
• Primary Completion (Anticipated): September 1, 2033
• Study Completion (Anticipated): September 1, 2035

Study Registration Dates

• First Submitted: July 14, 2018
• First Submitted That Met QC Criteria: August 23, 2018
• First Posted (Actual): August 24, 2018

Study Record Updates

• Last Update Posted (Actual): October 6, 2020
• Last Update Submitted That Met QC Criteria: October 5, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Disease Attributes; Neoplastic Processes; Pigmentation Disorders; Neoplasms; Recurrence; Telangiectasis; Hyperpigmentation; Neoplasm Recurrence, Local
• Other Study ID Numbers: DBCG RT Natural Trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: When the results from the trial are published, the DBCG RT Committee can decide that the results may be part of a meta-analysis.
• IPD Sharing Time Frame: It will only be possible if the DBCG Radiation Therapy Committee decides that it is acceptable
• IPD Sharing Access Criteria: The DBCG Radiation Therapy Committee will define the criteria after publication of the results from the trial
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

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