Clinical trial NCT04443413: Phase III Study of 5tx vs 15tx of RT (X-rays or Protons) Including RNI in Breast Cancer Patients
Official title: A Phase III Trial of Hypofractionated Radiotherapy to the Whole Breast or Post-Mastectomy Chest Wall Including Regional Nodal Irradiation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Anatomic Stage I Breast Cancer AJCC v8
Anatomic Stage II Breast Cancer AJCC v8
Anatomic Stage III Breast Cancer AJCC v8
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2020-06-23
Enrollment: 146
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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:

I. To determine the 24-month complication rate of 5 fraction radiotherapy compared to 25 fraction radiotherapy.

SECONDARY OBJECTIVES:

I. 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:

I. 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.

V. 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.

Eligibility criteria: Inclusion Criteria:

* 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)

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 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
* 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

Primary outcomes:
measure: Complication rate
timeFrame: At 24 months
Secondary outcomes:
measure: Incidence of acute adverse events
timeFrame: Up to 12 months post-radiation therapy
measure: Incidence of late toxicity
timeFrame: Up to 5 years post-radiation therapy
measure: Locoregional control
timeFrame: Up to 5 years post-radiation therapy
measure: Invasive disease-free survival
timeFrame: 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
measure: Disease-free survival
timeFrame: Up to 5 years post-radiation therapy
measure: Cause-specific survival
timeFrame: Up to 5 years post-radiation therapy
measure: Overall survival
timeFrame: Up to 5 years post-radiation therapy
Other outcomes:
measure: Cosmetic outcome
timeFrame: Up to 5 years post-radiation therapy
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Carlos E. Vargas, M.D.
role: PRINCIPAL_INVESTIGATOR
References: