A Trial of 15 Fraction vs 25 Fraction Pencil Beam Scanning Proton Radiotherapy After Mastectomy in Patients Requiring Regional Nodal Irradiation

A Randomized Trial of 15 Fraction vs 25 Fraction Pencil Beam Scanning Proton Radiotherapy After Mastectomy in Patients Requiring Regional Nodal Irradiation

This is a randomized controlled trial to determine the safety of 15 fraction vs 25 fraction pencil beam scanning proton radiotherapy after mastectomy in patients requiring regional nodal irradiation. Proton therapy is recognized as a standard option for the delivery of radiotherapy for breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: Hypofractionation

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

• Age ≥ 18 years
• Histologic confirmation of breast cancer resected by mastectomy with or without immediate reconstruction and chest wall and regional nodal irradiation planned.
• pStage T1-T4N0-N3M0 or ypStage T0-4N0-N3M0 Note: The axilla must be staged by sentinel node biopsy alone, sentinel node biopsy followed by axillary node dissection, or axillary lymph node dissection alone
• ECOG Performance Status (PS) 0 to 2. (Appendix I).
• Negative pregnancy test done ≤7 days prior to registration, for women of childbearing potential only.
• Radiotherapy must begin within 12 weeks of last surgery (breast or axilla) or last chemotherapy.

Note: Breast implants and expanders allowed

• Able to and provides IRB approved study specific written informed consent
• Ability to complete questionnaire (s) by themselves or with assistance
• Able to complete all mandatory tests listed in section 4.0
• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
• Willing to provide tissue and blood samples for correlative research purposes.
• Rochester and Arizona patients: Willing to sign consent onto the Mayo Clinic Radiotherapy Patient Outcomes Registry and Biobanking study, IRB number 15-000136
• Rochester patients: Willing to sign consent onto Evaluation of cardiac function in patients undergoing proton beam or photon radiotherapy, IRB number 15-007443

Exclusion Criteria:

• Medical contraindication to receipt of radiotherapy.
• Severe active co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or providing informed consent.
• Active systemic lupus or scleroderma.
• Pregnancy or women of childbearing potential who are sexually active and not willing/able to use medically acceptable forms of contraception
• Prior receipt of ipsilateral breast or chest wall radiation that would result in significant overlap of radiation therapy fields. Prior contralateral radiotherapy for breast cancer is allowed.
• Positive margins after definitive surgery
• History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior study entry
• Inflammatory breast cancer
• Recurrent Breast Cancer
• Boosts to the chest wall after mastectomy. Nodal boosts are 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
No Intervention: Conventional Fractionation; 50.0 Gy (RBE) in 25 daily fractions
Experimental: Hypofractionation; 40 Gy (RBE) in 15 daily fractions	Radiation: Hypofractionation; 40 Gy (RBE) in 15 daily fractions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complication Rate	Will be defined as the percentage of women randomized who develop one or more of the following events: grade 3 or higher late adverse events; unplanned surgical intervention (not including planned serial fat grafting) in patients who undergo mastectomy with reconstruction.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cosmesis	measured by reviewing digital photographs and the 4 point (excellent, good, fair, poor) adaptation of the Harvard Cosmesis Scale	baseline, 2 years, and 5 years
Incidence of Acute Adverse Events	Acute adverse events are defined using Common Terminology Criteria for Adverse Events (CTCAE) version 4. Grade 1 or 2 events occurring in at least 10% of patients are reported along with all grade 3 or higher events.	5 years
Incidence of Late Adverse Events	Late adverse events are defined using CTCAE version 4. Grade 1 or 2 events occurring in at least 10% of patients are reported along with all grade 3 or higher events.	5 years
Reconstruction Failure	A failure is defined as loss of the tissue expander or implant with the inability to replace it resulting in no final reconstruction or conversion to autologous reconstruction or revised with the addition of autologous reconstruction.	5 years
Quality of Life - Breast Cancer Outcomes	measured by cosmesis evaluation and the Breast Cancer Treatment Outcome Scale (BCTOS)	5 years
Ipsilateral Breast Tumor Recurrence (IBTR) Incidence	Will be defined as local recurrence from trial registration as a first event at 5 years. The IBTR cumulative incidence will be estimated using a competing risks method by treatment arm. The competing risks will be regional/distant breast cancer recurrence and death. The percentage of patients with IBTR is defined as the number of patients that have a IBTR divided by the number of patients treated in each arm.	5 years
Distant Recurrence Incidence	Will assess metastatic cancer that has either been biopsy confirmed or clinically diagnosed as recurrent invasive breast cancer at 5 years. The percentage of patients with a distant recurrence is defined as the number of patients that have a distant recurrence divided by the number of patients treated in each arm.	5 years
Regional Recurrence Incidence	Defined as invasive breast cancer in the axilla, regional lymph nodes, chest wall, and skin of the ipsilateral breast at 5 years. The percentage of patients with a regional recurrence is defined as the number of patients that have a regional recurrence divided by the number of patients treated in each arm.	5 years
Disease-free Survival (DFS) at 3 Years	DFS is defined as the time from study registration until the occurrence, if any, of one of the following events: invasive IBTR, regional invasive breast cancer recurrence, distant breast cancer recurrence, death due to any cause, contralateral invasive breast cancer, and second primary non-breast invasive disease. DFS at 3 years will be reported as the percent of patients without a DFS event at 3 years post radiotherapy.	3 years post radiotherapy, up to 38 months
Overall Survival (OS) at 3 Years	Overall survival is defined as the time from registration to death due to any cause. OS at 3 years is reported as the percentage of patients still alive and in follow up at 3 years post radiotherapy.	3 years post radiotherapy, up to 38 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Robert W. Mutter, M.D., Mayo Clinic

Publications and helpful links

General Publications

• Mutter RW, Giri S, Fruth BF, Remmes NB, Boughey JC, Harless CA, Ruddy KJ, McGee LA, Afzal A, Gao RW, Shumway DA, Vern-Gross TZ, Villarraga HR, Kenison SL, Kang Y, Wong WW, Stish BJ, Merrell KW, Yan ES, Park SS, Corbin KS, Vargas CE. Conventional versus hypofractionated postmastectomy proton radiotherapy in the USA (MC1631): a randomised phase 2 trial. Lancet Oncol. 2023 Oct;24(10):1083-1093. doi: 10.1016/S1470-2045(23)00388-1. Epub 2023 Sep 8.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2016
• Primary Completion (Actual): October 21, 2020
• Study Completion (Actual): November 18, 2023

Study Registration Dates

• First Submitted: May 19, 2016
• First Submitted That Met QC Criteria: May 25, 2016
• First Posted (Estimated): May 26, 2016

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: November 20, 2025
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Therapeutics; Radiotherapy; Dose Fractionation, Radiation; Radiotherapy Dosage; Radiation Dose Hypofractionation
• Other Study ID Numbers: 15-006137; MC1631 (Other Identifier: Mayo Clinic); NCI-2017-02362 (Registry Identifier: CTRP (Clinical Trial Reporting Program))