Proton Beam Radiation Therapy in Treating Patients With Breast Cancer After Surgery

Stage IIIC Breast Cancer AJCC v7 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03391453
• Other study ID #: MC1631
• Secondary ID: NCI-2017-02362MC
• Status: Recruiting
• Phase: Phase 2
• First received: December 29, 2017
• Last updated: December 29, 2017
• Start date: May 10, 2016
• Est. completion date: May 15, 2022

Study information

• Verified date: December 2017
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase II trial studies how well proton beam radiation therapy works in treating patients with breast cancer after surgery. Radiation therapy uses high energy protons to kill tumor cells and shrink tumors.

Description:

PRIMARY OBJECTIVES:

I. To determine whether the 24 month complication rate (defined as grade 3 or greater late adverse events; and unplanned surgical intervention in patients who undergo mastectomy with reconstruction) of 15 fraction chest wall and regional node pencil beam scanning proton radiotherapy is acceptable relative to 25 fraction chest wall and regional nodal pencil beam scanning proton radiotherapy and worthy of further investigation.

SECONDARY OBJECTIVES:

I. To evaluate acute and late toxicity. II. To evaluate the rate of reconstruction failure (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 unplanned revision with the addition of autologous reconstruction).

III. To determine the 5-year locoregional control, disease free survival and overall survival.

IV. To evaluate fatigue, arm function, and other patient reported outcomes. V. To evaluate clinical features, treatment technique, dose-volume parameters, histologic and genetic variants associated with fair and poor cosmetic outcome or unplanned surgical intervention.

VI. To compare echocardiographic changes, including left ventricular strain pattern, between fractionation regimens.

OUTLINE: Patients are randomized into 1 of 2 arms.

ARM I: Within 12 weeks of the last breast cancer surgery or the last dose of adjuvant chemotherapy and no sooner than 14 days since the last chemotherapy, patients receive conventionally fractionated proton beam radiation therapy daily for 25 fractions.

ARM II: Within 12 weeks of the last breast cancer surgery or the last dose of adjuvant chemotherapy and no sooner than 14 days since the last chemotherapy, patients receive hypofractionated proton beam radiation therapy daily for 15 fractions.

After completion of study treatment, patients are followed up at 12 weeks, at 12, 24, and 36 months, and at 5 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 82
• Est. completion date: May 15, 2022
• Est. primary completion date: May 15, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2

• 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 Institutional Review Board (IRB) approved study specific written informed consent

• Ability to complete questionnaire (s) by themselves or with assistance

• Able to complete all mandatory tests

• 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

Related Conditions & MeSH terms

• Breast Neoplasms
• Stage I Breast Cancer AJCC v7
• Stage IA Breast Cancer AJCC v7
• Stage IB Breast Cancer AJCC v7
• Stage II Breast Cancer AJCC v6 and v7
• Stage IIA Breast Cancer AJCC v6 and v7
• Stage IIB Breast Cancer AJCC v6 and v7
• Stage III Breast Cancer AJCC v7
• Stage IIIA Breast Cancer AJCC v7
• Stage IIIB Breast Cancer AJCC v7
• Stage IIIC Breast Cancer AJCC v7

Intervention

Radiation:
• Proton Beam Radiation Therapy
Receive conventionally fractionated radiotherapy
• Proton Beam Radiation Therapy
Receive hypofractionated radiotherapy

Other:
• Quality-of-Life Assessment
Ancillary studies

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota
United States	Mayo Clinic in Arizona	Scottsdale	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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. The complication rate will be estimated using a binomial estimator in both experimental arm and control arm, and a one-sided 90% confidence interval of the difference will be computed with normal approximation.	At 24 months
Secondary	Distant recurrence	Will assess metastatic cancer that has either been biopsy confirmed or clinically diagnosed as recurrent invasive breast cancer at 5 years. The distant breast cancer recurrence cumulative incidence will be estimated using a competing risks method (Gooley et al.) by treatment arm. The competing risks will be local/regional breast cancer recurrence and death.	At 5 years
Secondary	Incidence of acute adverse events	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.	Up to 90 days post radiation therapy
Secondary	Incidence of late adverse events	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.	Up to 5 years
Secondary	Invasive disease free survival	Will assess including 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. 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.	Time from study registration until the occurrence of one of the events in a composite endpoint, assessed up to 5 years
Secondary	Ipsilateral breast tumor recurrence (IBTR)	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 (Gooley et al.) by treatment arm. The competing risks will be regional/distant breast cancer recurrence and death.	At 5 years
Secondary	Overall 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.	Time from registration to death due to any cause, assessed up to 5 years
Secondary	Panel assessed cosmetic outcome	Cosmesis will be assessed by a panel of breast cancer medical providers using digital photographs.	Up to 2 years
Secondary	Patient reported outcomes	Elements of the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) will be used for patient self-reporting of toxicities. The Breast Cancer Treatment Outcomes Scale (BCTOS) will be used to measure patient reported functional status (pain, mobility). Other measures of fatigue, pain, and arm function will also be assessed. The comparison of the changes at each time point between the two treatment arms within each cohort will be done with a paired t-test or Wilcoxon signed rank test, whichever is appropriate.	Up to 5 years
Secondary	Patient self-reported cosmetic outcomes	Will be assessed using a modified Harvard Cosmesis Scale and a modified BCTOS. The values of the cosmesis instruments (patient self-reported and panel-assessed) will be summarized with the frequencies and confidence intervals of fair or poor cosmesis events at baseline, 2 years, and 5 years by treatment arm.	Up to 5 years
Secondary	Reconstruction failure	Will assess 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.	Up to 5 years
Secondary	Regional recurrence	Will assess invasive breast cancer in the axilla, regional lymph nodes, chest wall, and skin of the ipsilateral breast at 5 years. The regional breast cancer recurrence cumulative incidence will be estimated using a competing risks method (Gooley et al.) by treatment arm. The competing risks will be local/distant breast cancer recurrence and death.	At 5 years