Radiation Therapy With or Without Olaparib in Treating Patients With Inflammatory Breast Cancer

Breast Inflammatory Carcinoma Clinical Trial

Official title:

A Phase II Randomized Trial of Olaparib (NSC-747856) Administered Concurrently With Radiotherapy Versus Radiotherapy Alone for Inflammatory Breast Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03598257
• Other study ID #: NCI-2018-01519
• Secondary ID: NCI-2018-01519S1
• Status: Recruiting
• Phase: Phase 2
• Start date: January 18, 2019
• Est. completion date: June 1, 2027

Study information

• Verified date: March 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies how well radiation therapy with or without olaparib works in treating patients with inflammatory breast cancer. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. It is not yet known whether radiation therapy with or without olaparib may work better in treating patients with inflammatory breast cancer.

Description:

PRIMARY OBJECTIVE:

I. To compare the invasive disease-free survival (IDFS) of patients with inflammatory breast cancer receiving concurrent administration of olaparib with standard doses of radiotherapy to the chest wall and regional lymph nodes compared to standard doses of radiotherapy alone to the chest wall and regional lymph nodes.

SECONDARY OBJECTIVE:

I. To compare the effect of concurrent administration of olaparib with radiotherapy versus radiotherapy alone on improvement in locoregional control (measured by locoregional recurrence-free interval), distant relapse-free survival, and overall survival in inflammatory breast cancer patients.

ADDITIONAL OBJECTIVE:

I. To collect tissue and whole blood for processing and banking in anticipation of future correlative studies in this patient population.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I: Patients receive olaparib orally (PO) twice daily (BID) the day before standard radiation therapy (RT) commences (Day 0) and throughout the RT course until the last day of RT administration. Olaparib is also continued on weekends (routine days without RT) throughout the RT course. Patients undergo radiation therapy 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity.

GROUP II: Patients undergo standard radiation therapy 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection throughout the study.

After completion of study treatment, patients are followed up within 5 weeks, then every 3 months until 3 years after registration, and then every 6 months for up to 8 years after registration.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: June 1, 2027
• Est. primary completion date: June 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have inflammatory breast cancer without distant metastases. All biomarker subtype groups (estrogen receptor [ER], progesterone receptor [PR], HER2) are eligible. Inflammatory disease will be defined per American Joint Committee on Cancer (AJCC) 8th edition with documentation by history/exam and pathology at the time of diagnosis.

• All patients must have completed neoadjuvant chemotherapy prior to mastectomy. The chemotherapy regimen is at the discretion of the treating physician but it is recommended that it include at least 4 cycles of anthracycline and/or taxane-based therapy (plus targeted therapy for patients with HER2+ disease). Response to chemotherapy is not a criterion for eligibility (both complete responders and those with residual disease are eligible). Please note that although pathologic complete response (pCR) is not required or excluded, pCR status must be determined post-surgery prior to randomization.

• All patients must have undergone modified radical mastectomy (with negative margins on ink) with pathologic nodal evaluation (from level I and II axillary lymph node dissection [ALND]) at least 3 weeks and no more than 12 weeks prior to randomization, unless they receive additional chemotherapy after mastectomy. Patients must not have gross residual tumor or positive microscopic margins after mastectomy.

• Additional adjuvant chemotherapy after surgery is allowed at the discretion of the treating physician, either completed prior to randomization or planned for after completion of protocol treatment. If adjuvant chemotherapy is administered after mastectomy, the patient must be randomized at least 3 weeks but no more than 12 weeks after the last dose of adjuvant chemotherapy.

• Patients must not have a history of radiation therapy to the ipsilateral chest wall and/or regional nodes. Prior radiation therapy to other body sites is allowed.

• Patients must not be planning to receive any other investigational agents during radiation therapy. Prior therapy, including prior treatment with olaparib or other PARP inhibitor, is allowed.

• Patients must not have a known hypersensitivity to olaparib or any of the excipients of the product.

• Patients must not have unresolved or unstable grade 2 or greater toxicity (with the exception of alopecia) from prior administration of another investigational drug and/or prior anti-cancer treatment.

• Patients must not be planning to receive strong or moderate CYP3A inhibitors or inducers while on olaparib treatment. Patients receiving strong or moderate CYP3A inhibitors must agree to discontinue use at least 2 weeks prior to receiving olaparib. Patients receiving strong or moderate CYP3A inducers must agree to discontinue use at least 5 weeks prior to receiving olaparib.

• Patients must not be planning to receive live virus or live bacterial vaccines while receiving olaparib and during the 30 day follow up period

• Patients must not be planning to receive any additional anti-cancer therapy (chemotherapy, endocrine therapy, immunotherapy, biological therapy or other novel agent) while receiving radiotherapy with or without study medication. If a patient is receiving concurrent anti-HER2 targeted therapies, they must not take these medications during the period of radiotherapy (with or without study drug) while enrolled on the study.

• Patients must be >= 18 years of age

• Patients must have Zubrod performance status 0-2.

• Absolute neutrophil count (ANC) >= 1000/mm^3 (within 28 days prior to registration)

• Platelet count >= 100,000/mm^3 (within 28 days prior to registration)

• Hemoglobin >= 9.0 g/dL (after transfusion if required and within 28 days prior to registration)

• Patients must have adequate renal function as evidenced by calculated creatinine clearance >= 51 mL/min by Cockcroft-Gault equation, within 28 days prior to registration.

• Total bilirubin =< 1.5 x upper limit of normal (ULN) (within 28 days prior to registration)

• Patients with documented Gilbert's disease may have bilirubin up to 2.5 mg/dL

• Serum glutamic-oxaloacetic transaminase (SGOT) =< 2.5 x ULN (within 28 days prior to registration)

• Serum glutamate pyruvate transaminase (SGPT) =< 2.5 x ULN (within 28 days prior to registration)

• Alkaline phosphatase =< 2.5 x ULN (within 28 days prior to registration)

• Patients must not have a history of other prior malignancy except for the following:

adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years

• Female patients must be postmenopausal or have a negative urine or serum pregnancy test within 14 days prior to registration. Female patients of childbearing potential (and male patients with female partners who are of childbearing potential or pregnant) who are sexually active, must agree to the use of two highly effective forms of contraception during protocol treatment and for 6 months following the last dose of olaparib. Note: The efficacy of hormonal contraceptives may be reduced if co-administered with olaparib. Male patients must agree not to donate sperm during protocol treatment and for 6 months after the last dose of olaparib.

• Patients who are breastfeeding must agree to discontinue breastfeeding before receiving olaparib due to potential risk for adverse events in nursing infants secondary to treatment of the mother with olaparib.

• Patients must not have active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia.

• Patients must be able to swallow and retain oral medications and have no known gastrointestinal disorders likely to interfere with absorption of the study medication.

• Patients must not have a history of a resting electrocardiography (ECG) indicating uncontrolled, potentially reversible cardiac conditions (such as unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, Fridericia's formula corrected QT interval [QTcF] prolongation > 500 ms, electrolyte disturbances) or congenital long QCYP3T syndrome.

• Patients must not have myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML.

• Patient must not have had major surgery within 2 weeks of starting study treatments and patients must have recovered from any effects of any major surgery.

• Patients must not have a history of uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan.

• Patients must not have had previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).

• Patients must not have had whole blood transfusions in the last 120 days prior to randomization.

• Patients must be offered the opportunity to participate in specimen submission for banking.

• Note: Germline and somatic BRCA status (genetic testing) are planned for future correlative evaluation, in order to examine treatment and circulating tumor deoxyribonucleic acid (ctDNA) response as stratified by BRCA 1/2 mutational status. Since this is future planned correlative research, any mutational status results would not be returned to the patient or the treating physician. There is no Clinical Laboratory Improvement Act (CLIA)-certified clinical genetic testing being performed for patients as part of the S1706 study. A forthcoming revision or separate corelative sciences proposal would be submitted to and approved by National Cancer Institute (NCI) prior to conduct of any planned future translational medicine objectives.

• Patients who can complete the patient-reported outcomes (PRO) Quality of Life (QOL) and PRO-CTCAE questionnaires in English must be offered the opportunity to participate in the optional PRO substudy. Patients who are not able to complete questionnaires in English need not be offered the opportunity to participate.

• Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

• As a part of the OPEN registration process, the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.

Related Conditions & MeSH terms

• Breast Inflammatory Carcinoma

Intervention

Procedure:
• Biospecimen Collection
Undergo blood sample collection

Drug:
• Olaparib
Given PO

Radiation:
• Radiation Therapy
Undergo radiation therapy

Other:
• Survey Administration
Ancillary study

Locations

Country	Name	City	State
Canada	Jewish General Hospital	Montreal	Quebec
Canada	CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)	Quebec City	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Odette Cancer Centre- Sunnybrook Health Sciences Centre	Toronto	Ontario
Puerto Rico	Centro Comprensivo de Cancer de UPR	San Juan
Puerto Rico	San Juan Community Oncology Group	San Juan
United States	The Cancer Center of Hawaii-Pali Momi	'Aiea	Hawaii
United States	Lovelace Medical Center-Saint Joseph Square	Albuquerque	New Mexico
United States	Lovelace Radiation Oncology	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	The Don and Sybil Harrington Cancer Center	Amarillo	Texas
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Anchorage Associates in Radiation Medicine	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Trinity Health Saint Joseph Mercy Hospital Ann Arbor	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	ThedaCare Regional Cancer Center	Appleton	Wisconsin
United States	Hope Women's Cancer Centers-Asheville	Asheville	North Carolina
United States	Mission Hospital	Asheville	North Carolina
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	Rush - Copley Medical Center	Aurora	Illinois
United States	Mount Sinai Comprehensive Cancer Center at Aventura	Aventura	Florida
United States	IU Health West Hospital	Avon	Indiana
United States	UH Seidman Cancer Center at UH Avon Health Center	Avon	Ohio
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Saint Joseph's/Candler - Bluffton Campus	Bluffton	South Carolina
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Bozeman Health Deaconess Hospital	Bozeman	Montana
United States	Lafayette Family Cancer Center-EMMC	Brewer	Maine
United States	United Hospital Center	Bridgeport	West Virginia
United States	Trinity Health Medical Center - Brighton	Brighton	Michigan
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Trinity Health Medical Center - Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Carlisle Regional Cancer Center	Carlisle	Pennsylvania
United States	IU Health North Hospital	Carmel	Indiana
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
United States	Geauga Hospital	Chardon	Ohio
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Chelsea Hospital	Chelsea	Michigan
United States	Saint Luke's Hospital	Chesterfield	Missouri
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Case Western Reserve University	Cleveland	Ohio
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	MD Anderson in The Woodlands	Conroe	Texas
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Beaumont Hospital - Dearborn	Dearborn	Michigan
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Porter Adventist Hospital	Denver	Colorado
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Mayo Clinic Health System-Eau Claire Clinic	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Shaw Cancer Center	Edwards	Colorado
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Epic Care Partners in Cancer Care	Emeryville	California
United States	UPMC Hillman Cancer Center Erie	Erie	Pennsylvania
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Farmington Health Center	Farmington	Utah
United States	Beaumont Hospital - Farmington Hills	Farmington Hills	Michigan
United States	UPMC Cancer Center at UPMC Horizon	Farrell	Pennsylvania
United States	IU Health Central Indiana Cancer Centers-Fishers	Fishers	Indiana
United States	Beebe South Coastal Health Campus	Frankford	Delaware
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	CaroMont Regional Medical Center	Gastonia	North Carolina
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Altru Cancer Center	Grand Forks	North Dakota
United States	Corewell Health Grand Rapids Hospitals - Butterworth Hospital	Grand Rapids	Michigan
United States	Benefis Sletten Cancer Institute	Great Falls	Montana
United States	UPMC Cancer Centers - Arnold Palmer Pavilion	Greensburg	Pennsylvania
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Gulfport Memorial Hospital	Gulfport	Mississippi
United States	UPMC Pinnacle Cancer Center/Community Osteopathic Campus	Harrisburg	Pennsylvania
United States	Queen's Medical Center	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	M D Anderson Cancer Center	Houston	Texas
United States	MD Anderson West Houston	Houston	Texas
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	IU Health Methodist Hospital	Indianapolis	Indiana
United States	NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro	Jonesboro	Arkansas
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Kansas Cancer Center - North	Kansas City	Missouri
United States	University of Tennessee - Knoxville	Knoxville	Tennessee
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Mayo Clinic Health System-Franciscan Healthcare	La Crosse	Wisconsin
United States	University of Michigan Health - Sparrow Lansing	Lansing	Michigan
United States	Doctor's Hospital of Laredo	Laredo	Texas
United States	Memorial Medical Center - Las Cruces	Las Cruces	New Mexico
United States	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma
United States	MD Anderson League City	League City	Texas
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Los Angeles General Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Fremont - Rideout Cancer Center	Marysville	California
United States	UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion	Mechanicsburg	Pennsylvania
United States	Baptist Memorial Hospital and Cancer Center-Memphis	Memphis	Tennessee
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	UH Seidman Cancer Center at Southwest General Hospital	Middleburg Heights	Ohio
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	University Medical Center New Orleans	New Orleans	Louisiana
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Ascension Providence Hospitals - Novi	Novi	Michigan
United States	HSHS Saint Elizabeth's Hospital	O'Fallon	Illinois
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Cancer Specialists/Oncology Hematology West PC - MECC	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	Baptist Memorial Hospital and Cancer Center-Oxford	Oxford	Mississippi
United States	Desert Regional Medical Center	Palm Springs	California
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	The Valley Hospital - Luckow Pavilion	Paramus	New Jersey
United States	Parker Adventist Hospital	Parker	Colorado
United States	University Hospitals Parma Medical Center	Parma	Ohio
United States	Capital Health Medical Center-Hopewell	Pennington	New Jersey
United States	Sacred Heart Hospital	Pensacola	Florida
United States	Michigan Healthcare Professionals Pontiac	Pontiac	Michigan
United States	Trinity Health Saint Joseph Mercy Oakland Hospital	Pontiac	Michigan
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	University Hospitals Portage Medical Center	Ravenna	Ohio
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Valley Health System Ridgewood Campus	Ridgewood	New Jersey
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Pluta Cancer Center	Rochester	New York
United States	University of Rochester	Rochester	New York
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
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	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
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	UH Seidman Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania
United States	TidalHealth Nanticoke / Allen Cancer Center	Seaford	Delaware
United States	FHCC South Lake Union	Seattle	Washington
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Ascension Providence Hospitals - Southfield	Southfield	Michigan
United States	Baptist Memorial Hospital and Cancer Center-Desoto	Southhaven	Mississippi
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Springfield Regional Cancer Center	Springfield	Ohio
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	MD Anderson in Sugar Land	Sugar Land	Texas
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	Tampa General Hospital	Tampa	Florida
United States	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio
United States	Munson Medical Center	Traverse City	Michigan
United States	Upper Valley Medical Center	Troy	Ohio
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	University of Arizona Cancer Center-Orange Grove Campus	Tucson	Arizona
United States	Carle Cancer Center	Urbana	Illinois
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	University Hospitals Sharon Health Center	Wadsworth	Ohio
United States	George Washington University Medical Center	Washington	District of Columbia
United States	UH Seidman Cancer Center at Saint John Medical Center	Westlake	Ohio
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	University of Michigan Health - West	Wyoming	Michigan
United States	UPMC Memorial	York	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Invasive Disease-Free Survival (IDFS)	Time from date of registration to date of first invasive recurrence (local, regional or distant), second invasive primary cancer (breast or not), or death due to any cause. Patients last known to be alive who have not experienced recurrence or second primary cancer are censored at their last contact date. Analysis will be on an intent-to-treat basis and will estimate the survival endpoints using the product-limit method of Kaplan and Meier and will compare the time-to-event distributions using log-rank test statistics. Hazard ratios will be calculated from Cox regression analyses. Effect modification by the stratification variables will be tested as interactions with treatment and separate hazard ratios with 95% confidence intervals by major subgroups will be displayed in a forest plot to examine for consistency of the treatment effect over these subgroups.	Up to 8 years
Secondary	Locoregional Recurrence-Free Interval (Local Disease-Free Interval [LDFI])	Time from date of registration to date of invasive local or regional recurrence. Patients last known to be alive without recurrence are censored at their last contact date. Patients with distant recurrence, second primary cancer or death are censored at the time of that event. A competing risk framework will be conducted separating out the event types of locoregional recurrence from distant recurrence and death. Hazard ratios will be calculated from Cox regression analyses. Effect modification by the stratification variables will be tested as interactions with treatment and separate hazard ratios with 95% confidence intervals by major subgroups will be displayed in a forest plot to examine for consistency of the treatment effect over these subgroups.	Up to 8 years
Secondary	Distant Relapse-Free Survival (Distant Recurrence-Free Survival)	Time from date of registration to date of invasive distant disease recurrence, second invasive primary cancer (breast or not) or death due to any cause. Patients last known to be alive who have not experienced disease recurrence, or second primary cancer are censored at their last contact date.	Up to 8 years
Secondary	Overall Survival	Time from date of registration to date of death due to any cause. Patients last known to be alive are censored at their last contact date.	Up to 8 years