Testing Radiation and HER2-targeted Therapy Versus HER2-targeted Therapy Alone for Low-risk HER2-positive Breast Cancer

HER2-positive Breast Cancer Clinical Trial

— HERO  

Official title:

A Phase III Randomized Trial of Radiotherapy Optimization for Low-Risk HER2-Positive Breast Cancer (HERO)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05705401
• Other study ID #: NRG-BR008
• Secondary ID: 5U10CA180868NCI-
• Status: Recruiting
• Phase: Phase 3
• Start date: March 13, 2023
• Est. completion date: February 1, 2037

Study information

• Verified date: May 2024
• Source: NRG Oncology
• Contact: Director, Department of Regulatory Affairs
• Phone: 412-339-5300
• Email: langerj[@]nrgoncology.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This Phase III trial compares the recurrence-free interval (RFI) among patients with early-stage, low risk HER2+ breast cancer who undergo breast conserving surgery and receive HER2-directed therapy, and are randomized to not receive adjuvant breast radiotherapy versus those who are randomized to receive adjuvant radiotherapy per the standard of care.

Description:

The landmark trials that established breast conservation therapy (BCT) (breast-conserving surgery followed by adjuvant breast irradiation) as a suitable alternative to mastectomy were conducted in an era that predated biological subtyping of breast cancer and the use of HER2-directed therapies in patients with HER2+ cancers. These trials established adjuvant radiotherapy following breast-conserving surgery as necessary to maximize local control, yet, in the intervening years, overall outcomes have improved significantly owing to widespread adoption of screening mammography, resulting in a substantial reduction in average tumor size at diagnosis, as well as improvements in surgical techniques and, crucial for this proposal, the development of highly active systemic therapies.

Before the development of HER2-targeted therapies, patients with HER2-driven localized breast cancer had among the highest rates of local recurrence. However, with improved identification of these patients and the advent of HER2-directed therapies, outcomes have improved significantly, and trials have sought to optimize treatment to reduce the morbidity of both local and systemic treatment. Among the most salient of these examples is the APT trial, a single-arm adjuvant study that enrolled 410 breast cancer patients with HER2+ tumors ≤ 3cm in size and negative axillary nodes, who received adjuvant systemic therapy with weekly paclitaxel and trastuzumab for 12 weeks (TH) followed by 9 months of trastuzumab monotherapy. In addition to demonstrating a very low incidence of distant recurrence, among those on the trial who underwent BCT (lumpectomy and radiation, n = 244), only 2 local recurrence (LR) events have been reported after 7 years of follow-up (7-year LR = 1.2%), representing among the most favorable local outcomes of any breast cancer cohort studied to date. Confirmatory results are forthcoming from the ATEMPT trial, which evaluated the antibody-drug conjugate T-DM1 (ado-trastuzumab emtansine) (n=383) vs the TH regimen from the APT trial (n = 114), thus far showing only 3 LRs in each arm with a median 3-years of follow-up. Importantly, per the current standard of care for HER2+ patients undergoing BCT, all patients presumably received adjuvant breast radiotherapy.

The balance of the BCT literature, including a landmark meta-analysis by the Early Breast Cancer Trialists' Collaborative Group, suggests that adjuvant radiotherapy approximately halves the risk of local recurrence following lumpectomy across all analyzable subgroups. While the relative benefit appears constant across subgroups, the absolute benefit of adjuvant radiotherapy varies with the underlying risk. Taking the favorable results of the APT trial (1.2% 7-year LR), if one presumes that omission of radiotherapy yields a doubling or tripling of local recurrence (based on the observed RR of 0.5 - 0.66 for those receiving radiotherapy across the preponderance of historical trials), this population might have manifested a LR rate of 2.4 - 3.6% with the omission of radiotherapy. That is to say, the hypothesis is that administration of RT to APT patients undergoing BCT may have reduced the 7-year absolute risk of LR by only 1.2-2.4%. Through the identification of patients who are at low risk of LR, it may be acceptable for such patients to forego radiation. This hypothesis will be studied by evaluating omission of radiotherapy among patients with pT1N0 disease at breast-conserving surgery who receive adjuvant HER2-directed therapy (trastuzumab/paclitaxel preferred, other options per protocol), or with clinical tumors ≤ 3 cm and clinically negative axillary nodes (cN0) who achieve a pathologic complete response (pCR; ypT0N0) following preoperative (neoadjuvant) administration of HER2-directed therapy (trastuzumab/paclitaxel preferred, other options per protocol). It is expcted that the 5-year LR rate for this population omitting radiotherapy will be 2% or less, and that omission of radiation will not have a measurable impact on regional and distant recurrences or overall survival.

The practice of breast radiation oncology has benefited immensely from practice-changing trials that have refined the application of adjuvant radiotherapy since the early surgical studies determined whole breast radiotherapy to be necessary following lumpectomy. There are now several favorable breast cancer subtypes in which patients routinely forego radiotherapy after trials demonstrating modest benefits in terms of local recurrence and no impact on distant recurrence or survival, such as among small, low grade luminal cancers in older women and "good-risk" DCIS. Therefore, this will study the omission of radiotherapy among a population of HER2+ breast cancer patients who are now appreciated to also have favorable risk, so as to similarly weigh the attendant inconveniences, cost and morbidity of radiotherapy in light of an established absolute benefit, which may prove to be modest.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1300
• Est. completion date: February 1, 2037
• Est. primary completion date: February 1, 2034
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information.

• female and male patients who have undergone breast conserving surgery and completed a minimum of 4 cycles (12 weeks) of neoadjuvant or adjuvant chemotherapy in combination with HER2-targeted therapy.

-= 40 years of age

• ECOG performance status of 0 ,1, or 2/Karnofsky performance status above 60

• Histologically or cytologically confirmed invasive breast carcinoma.

• tumor must have been determined to be HER2-positive by current ASCO/CAP guidelines based on local testing results.

• Patient must have undergone axillary staging, either sentinel node biopsy (SNB) or axillary lymph nodal dissection (ALND). In neoadjuvant patients, SNB following neoadjuvant therapy is strongly recommended. SNB prior to neoadjuvant therapy is discouraged, but patients are permitted if node negative (pN0).

• The following staging criteria must be met according to AJCC 8th edition criteria:

Adjuvant cohort : By pathologic evaluation, the patient's primary tumor must be </= 2 cm and ipsilateral nodes must be pN0. Surgical lumpectomy margins must be negative for invasive cancer and ductal carcinoma in situ (no ink on tumor).

Neoadjuvant cohort: Prior to neoadjuvant therapy, the patient's primary tumor must be < 3 cm by imaging studies, with negative axillary nodes (cN0) based on axillary U/S, CT, PET or MRI. Physical examination is not sufficient documentation of cN0 status; • Must be ypT0N0 at surgery (lumpectomy); patients with residual non-invasive disease (DCIS) in the surgical specimen (ypTis), are NOT eligible.

• For the Adjuvant cohort, adjuvant therapy must have consisted of a minimum of 4 cycles (12 weeks) of chemotherapy in combination with HER2-targeted therapy.

• For the Neoadjuvant cohort, neoadjuvant therapy must have consisted of a minimum of 4 cycles (12 weeks) of chemotherapy in combination with HER2-targeted therapy.- ; Patients who did not receive chemotherapy in the neoadjuvant setting are not eligible, even if they achieved pCR with their preoperative treatment; nor would these patients become eligible by receiving chemotherapy after surgery.

• In patients assigned to radiation therapy, treatment should start = 12 weeks from surgery on the Neoadjuvant cohort and = 8 weeks from the completion of chemotherapy on the Adjuvant cohort. Patients should continue HER2-targeted therapy during assigned study treatment (radiation or observation).

• Bilateral mammogram or MRI within 52 weeks prior to randomization.

• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial.

Exclusion Criteria:

• Definitive clinical or radiologic evidence of metastatic disease.

• On the Adjuvant cohort, patients with a primary tumor >2 cm on pathologic examination of the surgical specimen. On the Neoadjuvant cohort, patients with a primary tumor > 3 cm or with abnormal or suspicious ipsilateral axillary nodes by pretreatment imaging, unless demonstrated to be negative by cytologic or histologic examination.

• Pathologically positive axillary nodes at any time including of pN0(i+) or pN0(mol+) ypN0(i+) or ypN0(mol+) disease.

• Patient planning for or status-post mastectomy.

• Radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary lymph nodes, unless there is histological confirmation that these nodes are negative for metastatic disease.

• Suspicious microcalcifications, densities, or palpable abnormalities (in the ipsilateral or contralateral breast), or mass or non-mass enhancement on MRI (if performed) aside from the known cancer, unless biopsied and found to be benign.

• Non-epithelial breast malignancies such as sarcoma or lymphoma.

• Multicentric carcinoma (invasive cancer or DCIS) in more than one quadrant or separated by > 4 centimeters. If multifocal, all foci should be confined to a maximum tumor bed of 3 cm determined by pathological assessment.

• Paget's disease of the nipple.

• Synchronous (unilateral or bilateral) invasive breast cancer or DCIS. (Patients with synchronous and/or previous contralateral LCIS are eligible.)

• On the Adjuvant cohort, surgical margins that cannot be microscopically assessed or are positive at pathologic evaluation. (If surgical margins are rendered free of disease by re-excision, the patient is eligible).

• Treatment plan that includes regional nodal irradiation.

• Patients treated for a prior invasive breast malignancy are excluded. Contralateral DCIS = 10 years prior to enrollment is permissible.

• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

• Patients on oral, transdermal, or subdermal estrogen replacement (including all estrogen only and estrogen-progesterone formulas) are not eligible unless discontinued prior to randomization.

• Prior ipsilateral breast or thoracic RT for any condition (contralateral RT for DCIS = 10 years prior to randomization is permitted).

• Active collagen vascular disease, specifically dermatomyositis with a CPK level above normal or with an active systemic lupus erythematosus, or scleroderma.

• Clinicians should consider whether any conditions would make this protocol unreasonably hazardous for the patient.

• Pregnancy or lactation at the time of randomization or intention to become pregnant during treatment. (Note: Pregnancy testing according to institutional standards for patients of childbearing potential must be performed within 14 days prior to randomization.)

• Use of any investigational product within 30 days prior to randomization.

Related Conditions & MeSH terms

• Breast Neoplasms
• HER2-positive Breast Cancer

Intervention

Radiation:
• Standard of Care Adjuvant Breast Radiation
adjuvant breast radiotherapy per the current standard of care

Drug:
• Standard of Care HER2-targeted Therapy Without Adjuvant Breast Radiation
participants are randomized to continue their standard of care systemic HER2-targeted therapy without adjuvant breast radiotherapy

Locations

Country	Name	City	State
Puerto Rico	Cancer Center-Metro Medical Center Bayamon	Bayamon
Puerto Rico	Doctors Cancer Center	Manati
Puerto Rico	Centro Comprensivo de Cancer de UPR	San Juan
Puerto Rico	San Juan City Hospital	San Juan
Puerto Rico	San Juan Community Oncology Group	San Juan
United States	The Cancer Center of Hawaii-Pali Momi	'Aiea	Hawaii
United States	Mission Cancer and Blood - Ankeny	Ankeny	Iowa
United States	Langlade Hospital and Cancer Center	Antigo	Wisconsin
United States	Kaiser Permanente-Deer Valley Medical Center	Antioch	California
United States	Mission Hope Medical Oncology - Arroyo Grande	Arroyo Grande	California
United States	Emory Proton Therapy Center	Atlanta	Georgia
United States	Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Grady Health System	Atlanta	Georgia
United States	John Fitzgerald Kennedy Medical Center	Atlantis	Florida
United States	Sutter Auburn Faith Hospital	Auburn	California
United States	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	UCHealth University of Colorado Hospital	Aurora	Colorado
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Indu and Raj Soin Medical Center	Beavercreek	Ohio
United States	Nebraska Medicine-Bellevue	Bellevue	Nebraska
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Saint Charles Health System	Bend	Oregon
United States	Tower Cancer Research Foundation	Beverly Hills	California
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Einstein Campus	Bronx	New York
United States	Montefiore Medical Center-Weiler Hospital	Bronx	New York
United States	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California
United States	Sands Cancer Center	Canandaigua	New York
United States	Cleveland Clinic Mercy Hospital	Canton	Ohio
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Caro Cancer Center	Caro	Michigan
United States	Physicians' Clinic of Iowa PC	Cedar Rapids	Iowa
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Saint Mary's Hospital	Centralia	Illinois
United States	Medical University of South Carolina	Charleston	South Carolina
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Michigan Healthcare Professionals Clarkston	Clarkston	Michigan
United States	Morton Plant Hospital	Clearwater	Florida
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Mission Cancer and Blood - West Des Moines	Clive	Iowa
United States	Baptist Memorial Hospital and Cancer Center-Collierville	Collierville	Tennessee
United States	Memorial Hospital North	Colorado Springs	Colorado
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Saint Francis Cancer Center	Colorado Springs	Colorado
United States	UCHealth Memorial Hospital Central	Colorado Springs	Colorado
United States	Baptist Memorial Hospital and Cancer Center-Golden Triangle	Columbus	Mississippi
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	MD Anderson in The Woodlands	Conroe	Texas
United States	Greater Regional Medical Center	Creston	Iowa
United States	Northwest Cancer Center - Main Campus	Crown Point	Indiana
United States	Noyes Memorial Hospital/Myers Cancer Center	Dansville	New York
United States	Carle at The Riverfront	Danville	Illinois
United States	Dayton Physician LLC - Englewood	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Premier Blood and Cancer Center	Dayton	Ohio
United States	Henry Ford Medical Center-Fairlane	Dearborn	Michigan
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Henry Ford Hospital	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Kaiser Permanente Dublin	Dublin	California
United States	Saint Luke's Hospital of Duluth	Duluth	Minnesota
United States	Northwest Oncology LLC	Dyer	Indiana
United States	University of Maryland Shore Medical Center at Easton	Easton	Maryland
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Farmington Health Center	Farmington	Utah
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	Michigan Healthcare Professionals Farmington	Farmington Hills	Michigan
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Cancer Care and Hematology-Fort Collins	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Lee Memorial Health System	Fort Myers	Florida
United States	Regional Cancer Center-Lee Memorial Health System	Fort Myers	Florida
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Kaiser Permanente-Fremont	Fremont	California
United States	Fresno Cancer Center	Fresno	California
United States	Kaiser Permanente-Fresno	Fresno	California
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Goshen Center for Cancer Care	Goshen	Indiana
United States	UCHealth Greeley Hospital	Greeley	Colorado
United States	Miami Valley Cancer Care and Infusion	Greenville	Ohio
United States	Baptist Cancer Center-Grenada	Grenada	Mississippi
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	UCHealth Highlands Ranch Hospital	Highlands Ranch	Colorado
United States	Northwest Cancer Center - Hobart	Hobart	Indiana
United States	Saint Mary Medical Center	Hobart	Indiana
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	M D Anderson Cancer Center	Houston	Texas
United States	MD Anderson West Houston	Houston	Texas
United States	City of Hope at Irvine Lennar	Irvine	California
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Allegiance Health	Jackson	Michigan
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Kansas Cancer Center - North	Kansas City	Missouri
United States	Kettering Medical Center	Kettering	Ohio
United States	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois
United States	City of Hope Antelope Valley	Lancaster	California
United States	MD Anderson League City	League City	Texas
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	Cancer Partners of Nebraska	Lincoln	Nebraska
United States	Cancer Partners of Nebraska - Pine Lake	Lincoln	Nebraska
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Los Angeles General Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Medical Center of the Rockies	Loveland	Colorado
United States	Michigan Healthcare Professionals Macomb	Macomb	Michigan
United States	University of Wisconsin Carbone Cancer Center - University Hospital	Madison	Wisconsin
United States	Michigan Healthcare Professionals Madison Heights	Madison Heights	Michigan
United States	Saint Mary's Oncology/Hematology Associates of Marlette	Marlette	Michigan
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Loyola University Medical Center	Maywood	Illinois
United States	Bon Secours Memorial Regional Medical Center	Mechanicsville	Virginia
United States	Baptist Memorial Hospital and Cancer Center-Memphis	Memphis	Tennessee
United States	Froedtert Menomonee Falls Hospital	Menomonee Falls	Wisconsin
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Bon Secours Saint Francis Medical Center	Midlothian	Virginia
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Kaiser Permanente-Modesto	Modesto	California
United States	Memorial Medical Center	Modesto	California
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Palo Alto Medical Foundation-Camino Division	Mountain View	California
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	The Community Hospital	Munster	Indiana
United States	Women's Diagnostic Center - Munster	Munster	Indiana
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Baptist Memorial Hospital and Cancer Center-Union County	New Albany	Mississippi
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	CTCA at Southeastern Regional Medical Center	Newnan	Georgia
United States	University of Kansas Cancer Center at North Kansas City Hospital	North Kansas City	Missouri
United States	Henry Ford Medical Center-Columbus	Novi	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	HSHS Saint Elizabeth's Hospital	O'Fallon	Illinois
United States	Drexel Town Square Health Center	Oak Creek	Wisconsin
United States	Kaiser Permanente Oakland-Broadway	Oakland	California
United States	Kaiser Permanente-Oakland	Oakland	California
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Olathe Health Cancer Center	Olathe	Kansas
United States	Nebraska Medicine-Village Pointe	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	University of Kansas Hospital-Indian Creek Campus	Overland Park	Kansas
United States	Baptist Memorial Hospital and Cancer Center-Oxford	Oxford	Mississippi
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
United States	UPMC-Magee Womens Hospital	Pittsburgh	Pennsylvania
United States	GenesisCare USA - Plantation	Plantation	Florida
United States	Pomona Valley Hospital Medical Center	Pomona	California
United States	Trinity Health Saint Joseph Mercy Oakland Hospital	Pontiac	Michigan
United States	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Kaiser Permanente-Rancho Cordova Cancer Center	Rancho Cordova	California
United States	Kaiser Permanente- Marshall Medical Offices	Redwood City	California
United States	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Bon Secours Cancer Institute at Reynolds Crossing	Richmond	Virginia
United States	Bon Secours Saint Mary's Hospital	Richmond	Virginia
United States	Kaiser Permanente-Richmond	Richmond	California
United States	Reid Health	Richmond	Indiana
United States	Highland Hospital	Rochester	New York
United States	Pluta Cancer Center	Rochester	New York
United States	University of Rochester	Rochester	New York
United States	Wilmot Cancer Institute Radiation Oncology at Greece	Rochester	New York
United States	Rohnert Park Cancer Center	Rohnert Park	California
United States	Kaiser Permanente-Roseville	Roseville	California
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	Sutter Roseville Medical Center	Roseville	California
United States	The Permanente Medical Group-Roseville Radiation Oncology	Roseville	California
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Kaiser Permanente Downtown Commons	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	South Sacramento Cancer Center	Sacramento	California
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan
United States	Dartmouth Cancer Center - North	Saint Johnsbury	Vermont
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Salina Regional Health Center	Salina	Kansas
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	University of Utah Sugarhouse Health Center	Salt Lake City	Utah
United States	California Pacific Medical Center-Pacific Campus	San Francisco	California
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Stanford Cancer Center South Bay	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California
United States	Kaiser San Rafael-Gallinas	San Rafael	California
United States	Ridley-Tree Cancer Center	Santa Barbara	California
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	City of Hope South Pasadena	South Pasadena	California
United States	Kaiser Permanente Cancer Treatment Center	South San Francisco	California
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Baptist Memorial Hospital and Cancer Center-Desoto	Southhaven	Mississippi
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Kaiser Permanente-Stockton	Stockton	California
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	MD Anderson in Sugar Land	Sugar Land	Texas
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California
United States	BJC Outpatient Center at Sunset Hills	Sunset Hills	Missouri
United States	Ascension Saint Joseph Hospital	Tawas City	Michigan
United States	University of Kansas Health System Saint Francis Campus	Topeka	Kansas
United States	City of Hope South Bay	Torrance	California
United States	Torrance Memorial Physician Network - Cancer Care	Torrance	California
United States	Dayton Physicians LLC - Troy	Troy	Ohio
United States	Michigan Healthcare Professionals Troy	Troy	Michigan
United States	Upper Valley Medical Center	Troy	Ohio
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Memorial Sloan Kettering Nassau	Uniondale	New York
United States	City of Hope Upland	Upland	California
United States	Carle Cancer Center	Urbana	Illinois
United States	Kaiser Permanente Medical Center-Vacaville	Vacaville	California
United States	South Georgia Medical Center/Pearlman Cancer Center	Valdosta	Georgia
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	Northwest Cancer Center - Valparaiso	Valparaiso	Indiana
United States	Legacy Cancer Institute Medical Oncology and Day Treatment	Vancouver	Washington
United States	Legacy Salmon Creek Hospital	Vancouver	Washington
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Kent Hospital	Warwick	Rhode Island
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	Wilmot Cancer Institute at Webster	Webster	New York
United States	Froedtert West Bend Hospital/Kraemer Cancer Center	West Bend	Wisconsin
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	Saint Mary's Oncology/Hematology Associates of West Branch	West Branch	Michigan
United States	Lexington Medical Center	West Columbia	South Carolina
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Aspirus Cancer Care - Wisconsin Rapids	Wisconsin Rapids	Wisconsin
United States	Midwestern Regional Medical Center	Zion	Illinois

Sponsors (5)

Lead Sponsor	Collaborator
NRG Oncology	Alliance for Clinical Trials in Oncology, Eastern Cooperative Oncology Group, National Cancer Institute (NCI), SWOG Cancer Research Network

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	recurrence-free interval (RFI)	Time to recurrence event or censoring	From randomization to first recurrence event or censoring for the duration of the trial, at 10.5 years
Secondary	ipsilateral breast recurrence (IBR) for radiation omitting arm	Time to IBTR event or censoring	From randomization to first recurrence event or censoring for the duration of the trial , measured at year 7
Secondary	ipsilateral breast recurrence (IBR) by treatment arm	Time to ipsilateral breast recurrence (IBR) by treatment arm.	From randomization to first recurrence event or censoring for the duration of the trial at 10.5 years.
Secondary	local regional recurrence (LRR) by treatment arm	Time to local regional recurrence (LRR) by treatment arm.	From randomization to first recurrence event or censoring for the duration of the trial at 10.5 years.
Secondary	disease-free survival (DFS) by treatment arm.	To determine disease-free survival (DFS) by treatment arm.	From the time of randomization for the duration of the trial at 10.5 years.
Secondary	overall survival (OS) by treatment arm.	To determine overall survival (OS) by treatment arm.	From the time of randomization for the duration of the trial at 10.5 years.
Secondary	patient-reported breast pain by treatment arm using the Breast Cancer Treatment Outcome Scale (BCTOS)	To evaluate whether there is a difference in patient-reported breast pain in patients who do and do not receive breast radiation in cohort A and cohort B. The BCTOS pain score has a range from 1-5 with higher scores indicating worse pain.	At 3 years after randomization
Secondary	patient-reported worry about recurrence by treatment arm using a the three-item worry about recurrence score	To evaluate whether there is a difference in patient-reported worry about recurrence in patients who do and do not receive breast radiation in cohort A and cohort B. The worry about recurrence score has a range from 1-5 with higher scores indicating more worry.	At 3 years after randomization