Anatomic Stage I Breast Cancer AJCC v8Phase 3NCT04443413
Phase III Study of 5tx vs 15tx of RT (X-rays or Protons) Including RNI in Breast Cancer Patients
A Phase 3 study testing Proton Beam Radiation Therapy, Questionnaire Administration and X-ray Therapy in people with Anatomic Stage I Breast Cancer AJCC v8 and Anatomic Stage II Breast Cancer AJCC v8, run by Mayo Clinic at 3 sites in United States.
Trial summary
This phase III trial compares the rate of complications of x-ray therapy versus proton beam radiation therapy after breast conserving surgery or mastectomy in treating patients with breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8
- What is being tested?
- Proton Beam Radiation Therapy, Questionnaire Administration and X-ray Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 146 participants
- Where
- 3 sitesUnited States
- Study dates
- 16 Jun 2020to 19 Nov 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >= 18 years
- Histological confirmation of breast cancer
- Breast conserving surgery or mastectomy (reconstruction is allowed)
- Clinical or pathologic T1-T4c, N0-3, M0 disease
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2
- Able to and provides Institutional Review Board (IRB) approved study specific written informed consent
- Indications for breast or post mastectomy radiation with regional nodal radiotherapy per the discretion of the treating physician
- If uncertain of eligibility please consult the principal investigator (PI)
Who cannot join
- Medical contraindication to receipt of radiotherapy
- Severe active co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator or PI, 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
- Prior receipt of ipsilateral breast or chest wall radiation
- Persistent positive margins on ink after definitive surgery either for ductal carcinoma in situ (DCIS) or invasive cancer
Show all 12Show fewer
- No active metastatic disease from other origin
- Recurrent breast cancer
- Patient requires bilateral breast radiation treatment
- cT4d patients (inflammatory breast cancer)
- Patients that may not be compliant or fit for the study at the discretion of the PI
- Male patients
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259
About this study
Official title: A Phase III Trial of Hypofractionated Radiotherapy to the Whole Breast or Post-Mastectomy Chest Wall Including Regional Nodal Irradiation
This phase III trial compares the rate of complications of x-ray therapy versus proton beam radiation therapy after breast conserving surgery or mastectomy in treating patients with breast cancer. X-ray therapy is a form of radiation therapy that uses high-energy radiation from x-rays to kill tumor cells and shrink tumors. Proton beam radiation therapy is a type of radiation therapy that uses high-energy beams to treat tumors. It is not yet known what level of complications x-ray therapy or proton beam radiation therapy have in treating patients with breast cancer.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine the 24-month complication rate of 5 fraction radiotherapy compared to 25 fraction radiotherapy.
SECONDARY OBJECTIVES:
- To evaluate acute toxicity that occur up to 12 months after radiation. II. To evaluate late toxicity that appear or persist 12 months after radiation. III. To estimate the 5-year locoregional control, invasive disease-free survival, disease-free survival, cause-specific survival and overall survival.
CORRELATIVE AND EXPLORATORY OBJECTIVES:
- To evaluate patient-reported quality of life outcomes through Mayo Breast Survey, Mayo 10 (Patient-Reported Outcomes [PRO]-Common Terminology Criteria for Adverse Events [CTCAE]), and Mayo Patient Survey.
II. To evaluate clinical features, treatment technique, dose-volume parameters, histologic and genetic variants associated with fair and poor cosmetic outcomes or unplanned surgical intervention.
III. To evaluate the costs and comparative effectiveness of treatment. IV. Compare the use of photon therapy with spot scanning proton therapy hypo-fractionated whole breast or post-mastectomy chest wall with regional nodal irradiation.
- To evaluated cosmetic outcome with patient-reported measures with elements from the Mayo Breast Patient Survey and panel assess cosmetic outcome with blinded photographs, and the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/Radiation Therapy Oncology Group (RTOG) Cosmesis Scale.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Within 12 weeks of the last breast cancer surgery or last dose of adjuvant chemotherapy and no sooner than 14 days since the last chemotherapy, patients undergo x-ray therapy over 25 fractions in the absence of disease progression or unacceptable toxicity. Optionally, patients may then receive a 4-fraction boost of x-ray therapy.
ARM II: Within 12 weeks of the last breast cancer surgery or last dose of adjuvant chemotherapy and no sooner than 14 days since the last chemotherapy, patients undergo proton beam radiation therapy over 5 fractions in the absence of disease progression or unacceptable toxicity. Optionally, patients may receive a concurrent 5-fraction boost of proton beam radiation therapy.
After completion of study treatment, patients are followed up at 12 weeks, at 6, 12, 24, and 36 months, and then at 5 years.
- Conditions
- Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8
- Being tested
- Proton Beam Radiation Therapy, Questionnaire Administration, X-ray Therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Proton Beam Radiation TherapyRadiation
Also called PBRT, Proton, Proton EBRT, Proton External Beam Radiotherapy
Undergo proton beam radiation therapy
Questionnaire AdministrationOther
Ancillary studies
X-ray TherapyRadiation
Also called X-ray Radiation Therapy
Undergo x-ray therapy
| Study group | Role | What they receive |
|---|---|---|
| Arm I (x-ray therapy) | Experimental | Within 12 weeks of the last breast cancer surgery or last dose of adjuvant chemotherapy and no sooner than 14 days since the last chemotherapy, patients undergo x-ray therapy over 25 fractions in the absence of disease progression or unacceptable toxicity. Optionally, patients may then receive a 4-fraction boost of x-ray therapy. Receives: Other: Questionnaire Administration; Radiation: X-ray Therapy |
| Arm II (proton beam radiation therapy) | Experimental | Within 12 weeks of the last breast cancer surgery or last dose of adjuvant chemotherapy and no sooner than 14 days since the last chemotherapy, patients undergo proton beam radiation therapy over 5 fractions in the absence of disease progression or unacceptable toxicity. Optionally, patients may receive a concurrent 5-fraction boost of proton beam radiation therapy. Receives: Radiation: Proton Beam Radiation Therapy; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complication rate
Will be defined as the percentage of women evaluable at 24 months who develop one or more of these events: grade 3 or higher late adverse event or unplanned surgeries for cosmetic or treatment related events, including surgeries to remove implant.
Measured: At 24 months
Secondary outcomes (7)
Incidence of acute adverse events
The maximum grade for each type of acute adverse event will be recorded for each patient. Data will be summarized as frequencies and relative frequencies by treatment arm. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Rates will be compared between arms using chi-squared tests.
Measured: Up to 12 months post-radiation therapy
Incidence of late toxicity
Will be defined as any adverse event that occurred or persisted after the first 12 months post-radiation therapy and up to 5 years post-radiation therapy. The maximum grade for each type of late adverse event will be recorded for each patient. Data will be summarized as frequencies and relative frequencies by treatment arm. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Rates will be compared between arms using chi-squared tests.
Measured: Up to 5 years post-radiation therapy
Locoregional control
The cumulative incidence of locoregional recurrence will be estimated using a competing risks method by treatment arm. The competing risks will be distant breast cancer recurrence and death. Comparison between arms will employ Fine-Gray regression.
Measured: Up to 5 years post-radiation therapy
Invasive disease-free survival
Invasive disease recurrence is defined by ipsilateral breast tumor recurrence (IBTR), regional recurrence, or distant recurrence. Will be estimated with a Kaplan-Meier estimator and curve by treatment arm. Estimates will be given for specific time points along with 95% confidence intervals. Comparison between arms will employ a log-rank test.
Measured: From study registration until the time of invasive disease recurrence (not including ductal carcinoma in situ) or death due to any cause, assessed up to 5 years post-radiation therapy
Disease-free survival
Defined as the time from registration until the time of disease recurrence or death due to any cause. Will be estimated with a Kaplan-Meier estimator and curve by treatment arm. Estimates will be given for specific time points along with 95% confidence intervals. Comparison between arms will employ a log-rank test.
Measured: Up to 5 years post-radiation therapy
Cause-specific survival
Will be estimated with a Kaplan-Meier estimator and curve by treatment arm. Estimates will be given for specific time points along with 95% confidence intervals. Comparison between arms will employ a log-rank test.
Measured: Up to 5 years post-radiation therapy
Overall survival
Defined as the time from registration to death due to any cause. Will be estimated with a Kaplan-Meier estimator and curve by treatment arm. Estimates will be given for specific time points along with 95% confidence intervals. Comparison between arms will employ a log-rank test.
Measured: Up to 5 years post-radiation therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2020
- Study start16 Jun 2020
- Primary completion19 Nov 2026 (estimated)
- Study completion19 Nov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anatomic Stage I Breast Cancer AJCC v8Studies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 146 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Carlos E. Vargas, M.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04443413
- Sponsor's protocol ID
- MC1935
- Other IDs
- NCI-2020-04328, MC1935, 19-008858
- Status last verified
- Jan 2026
- First submitted
- 19 Jun 2020
- Last updated
- 16 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Trial of Hypofractionated Radiotherapy to the Whole Breast or Post-Mastectomy Chest Wall Including Regional Nodal Irradiation
- ClinicalTrials.gov ID
- NCT04443413
- Acronym / sponsor ID
- MC1935
- Conditions
- Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 146 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 16 Jun 2020 (actual)
- Primary completion
- 19 Nov 2026 (estimated)
- Study completion
- 19 Nov 2029 (estimated)
- First posted
- 23 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase III trial compares the rate of complications of x-ray therapy versus proton beam radiation therapy after breast conserving surgery or mastectomy in treating patients with breast cancer. X-ray therapy is a form of radiation therapy that uses high-energy radiation from x-rays to kill tumor cells and shrink tumors. Proton beam radiation therapy is a type of radiation therapy that uses high-energy beams to treat tumors. It is not yet known what level of complications x-ray therapy or proton beam radiation therapy have in treating patients with breast cancer.
Detailed description
PRIMARY OBJECTIVE:
- To determine the 24-month complication rate of 5 fraction radiotherapy compared to 25 fraction radiotherapy.
SECONDARY OBJECTIVES:
- To evaluate acute toxicity that occur up to 12 months after radiation. II. To evaluate late toxicity that appear or persist 12 months after radiation. III. To estimate the 5-year locoregional control, invasive disease-free survival, disease-free survival, cause-specific survival and overall survival.
CORRELATIVE AND EXPLORATORY OBJECTIVES:
- To evaluate patient-reported quality of life outcomes through Mayo Breast Survey, Mayo 10 (Patient-Reported Outcomes [PRO]-Common Terminology Criteria for Adverse Events [CTCAE]), and Mayo Patient Survey.
II. To evaluate clinical features, treatment technique, dose-volume parameters, histologic and genetic variants associated with fair and poor cosmetic outcomes or unplanned surgical intervention.
III. To evaluate the costs and comparative effectiveness of treatment. IV. Compare the use of photon therapy with spot scanning proton therapy hypo-fractionated whole breast or post-mastectomy chest wall with regional nodal irradiation.
- To evaluated cosmetic outcome with patient-reported measures with elements from the Mayo Breast Patient Survey and panel assess cosmetic outcome with blinded photographs, and the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/Radiation Therapy Oncology Group (RTOG) Cosmesis Scale.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Within 12 weeks of the last breast cancer surgery or last dose of adjuvant chemotherapy and no sooner than 14 days since the last chemotherapy, patients undergo x-ray therapy over 25 fractions in the absence of disease progression or unacceptable toxicity. Optionally, patients may then receive a 4-fraction boost of x-ray therapy.
ARM II: Within 12 weeks of the last breast cancer surgery or last dose of adjuvant chemotherapy and no sooner than 14 days since the last chemotherapy, patients undergo proton beam radiation therapy over 5 fractions in the absence of disease progression or unacceptable toxicity. Optionally, patients may receive a concurrent 5-fraction boost of proton beam radiation therapy.
After completion of study treatment, patients are followed up at 12 weeks, at 6, 12, 24, and 36 months, and then at 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (x-ray therapy) | Experimental | Other: Questionnaire Administration, Radiation: X-ray TherapyWithin 12 weeks of the last breast cancer surgery or last dose of adjuvant chemotherapy and no sooner than 14 days since the last chemotherapy, patients undergo x-ray therapy over 25 fractions in the absence of disease progression or unacceptable toxicity. Optionally, patients may then receive a 4-fraction boost of x-ray therapy. |
| Arm II (proton beam radiation therapy) | Experimental | Radiation: Proton Beam Radiation Therapy, Other: Questionnaire AdministrationWithin 12 weeks of the last breast cancer surgery or last dose of adjuvant chemotherapy and no sooner than 14 days since the last chemotherapy, patients undergo proton beam radiation therapy over 5 fractions in the absence of disease progression or unacceptable toxicity. Optionally, patients may receive a concurrent 5-fraction boost of proton beam radiation therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age >= 18 years
- Histological confirmation of breast cancer
- Breast conserving surgery or mastectomy (reconstruction is allowed)
- Clinical or pathologic T1-T4c, N0-3, M0 disease
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2
Key exclusion criteria (12 listed)
- Medical contraindication to receipt of radiotherapy
- Severe active co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator or PI, 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
- Prior receipt of ipsilateral breast or chest wall radiation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Proton Beam Radiation TherapyAlso: PBRT, Proton, Proton EBRT, Proton External Beam RadiotherapyUndergo proton beam radiation therapy | Radiation | Arm II (proton beam radiation therapy) |
| Questionnaire AdministrationAncillary studies | Other | Arm I (x-ray therapy), Arm II (proton beam radiation therapy) |
| X-ray TherapyAlso: X-ray Radiation TherapyUndergo x-ray therapy | Radiation | Arm I (x-ray therapy) |
Primary outcome
Complication rate
Time frame: At 24 months
Will be defined as the percentage of women evaluable at 24 months who develop one or more of these events: grade 3 or higher late adverse event or unplanned surgeries for cosmetic or treatment related events, including surgeries to remove implant.
7 secondary outcomes
Incidence of acute adverse events
Time frame: Up to 12 months post-radiation therapy
Incidence of late toxicity
Time frame: Up to 5 years post-radiation therapy
Locoregional control
Time frame: Up to 5 years post-radiation therapy
Invasive disease-free survival
Time frame: From study registration until the time of invasive disease recurrence (not including ductal carcinoma in situ) or death due to any cause, assessed up to 5 years post-radiation therapy
Disease-free survival
Time frame: Up to 5 years post-radiation therapy
Cause-specific survival
Time frame: Up to 5 years post-radiation therapy
Overall survival
Time frame: Up to 5 years post-radiation therapy
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2026.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
Related trials for Anatomic Stage I Breast Cancer AJCC v8
RecruitingObservational study
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
RecruitingPhase 2
Dose-Reduced Docetaxel With Cyclophosphamide for the Treatment of Vulnerable Older Women With Stage I-III HER2 Negative Breast Cancer, the DOROTHY Trial
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8
RecruitingPhase 2
Ph2 Study for Optimization of Adjunct Systemic Therapy in HER2+ Patients, MolecularPCR Trial
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8
Recruiting
Researching the Effect of Exercise on Cancer
Breast Cancer, Prostate Cancer
RecruitingPhase 1/2
Ivermectin in Combination With Balstilimab or Pembrolizumab in Patients With Metastatic Triple Negative Breast Cancer and HR+/HER2- Metastatic Breast Cancer
Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Triple-Negative Breast Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carlos E. Vargas, M.D. principal investigator
Mayo Clinic
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Proton Beam Radiation Therapy, Questionnaire Administration and X-ray Therapy in people with Anatomic Stage I Breast Cancer AJCC v8 and Anatomic Stage II Breast Cancer AJCC v8, run by Mayo Clinic at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 16 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complication rate (time frame: At 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2026.