Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Hormone Therapy With or Without Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Negative Breast Cancer (The TAILORx Trial)

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active 18 to 75 NCI ECOG-PACCT-1 SWOG-ECOG-PACCT-1, CALGB-ECOG-PACCT-1, NCCTG-ECOG-PACCT-1, NSABP-ECOG-PACCT-1, ACOSOG-ECOG-PACCT-1, CAN-NCIC-MAC12, PACCT-1, NCT00310180, TAILORx

Special Category: NCI Web site featured trial, CTSU trial

Objectives

Primary

1. Compare the disease-free survival of women with previously resected axillary-node negative breast cancer with an Oncotype DX Recurrence Score (ODRS) of 11-25 treated with adjuvant combination chemotherapy and hormonal therapy vs adjuvant hormonal therapy alone.
2. Compare the distant recurrence-free interval, recurrence-free interval, and overall survival of patients with an ODRS of 11-25 treated with these regimens.
3. Create a tissue and specimen bank that includes formalin-fixed, paraffin-embedded tumor specimens, tissue microarrays, plasma, and DNA obtained from peripheral blood of patients enrolled in this trial.

Secondary

1. Determine if adjuvant hormonal therapy alone is sufficient treatment (i.e., 10-year distant disease-free survival of at least 95%) for patients with an ODRS of ≤ 10.
2. Determine the disease-free survival, distant recurrence-free interval, recurrence-free interval, and overall survival of patients with ODRS of ≤ 10.
3. Compare the outcomes projected at 10 years using classical pathologic information, including tumor size, hormone receptor status, and histologic grade, with those made by the Genomic Health Oncotype DX test in patients treated with these regimens.
4. Estimate failure rates as a function of ODRS separately in patients treated with combination chemotherapy (group 2/arm II and group 3) and in patients treated with no chemotherapy (group 1 and group 2/arm I).
5. Determine the prognostic significance of the ODRS and of the individual recurrent score gene groups (proliferation gene group, HER2 gene group, estrogen receptor gene group, invasion gene group, and other genes) in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically confirmed adenocarcinoma of the breast



• Hormone receptor status: estrogen and/or progesterone receptor positive tumor



• Her2/neu negative tumor by either fluorescent in situ hybridization (FISH) or immunohistochemistry (e.g., 0 or 1+ by DAKO Herceptest)



• Must have undergone surgery to remove the primary tumor by either a modified radical mastectomy or local excision plus an acceptable axillary procedure (i.e., sentinel lymph node biopsy and/or axillary dissection) within the past 84 days
  • Must have adequate (i.e., ≥ 1 mm, if margin width specified) tumor-free margins of resection for invasive and ductal carcinoma in situ
    • Lobular carcinoma in situ involving the resection margins are allowed
  • Negative axillary nodes as determined by a sentinel lymph node biopsy and/or axillary dissection as defined by the American Joint Committee on Cancer sixth edition staging system



• Tumor size 1.1-5.0 cm
  • Tumors that measure 5 mm-1.0 cm are allowed provided there are unfavorable histological features, defined as intermediate or poor nuclear and/or histologic grade or lymphovascular invasion
  • Pathologic tumor size should be used
    • If microscopic measurement is used and tumor includes ductal carcinoma in situ, the measurement should include only the invasive component of the tumor



• Tissue specimen from the primary tumor available for diagnostic testing with Oncotype DX to determine Oncotype Recurrence Score
  • No prior Oncotype DX Assay unless patient has a recurrence score of 11-25



• Patients who develop breast cancer while receiving a selective estrogen-receptor modulator (SERM) (e.g., tamoxifen, toremifene, or raloxifene) or an aromatase inhibitor (e.g., anastrazole, letrozole, or exemestane) for breast cancer prevention or a SERM for other indications (e.g., raloxifene for osteoporosis) are ineligible



• No prior ipsilateral or contralateral invasive breast cancer, bilateral synchronous cancers, or prior ipsilateral or contralateral ductal carcinoma in situ

Prior/Concurrent Therapy:

• See Disease Characteristics
• No prior chemotherapy or radiotherapy (including MammoSite^® brachytherapy radiotherapy) for this cancer
• Prior SERM or aromatase inhibitor therapy that was administered for up to 8 weeks for this cancer is allowed
• No concurrent radiotherapy with chemotherapy
• Concurrent enrollment on another CTSU study allowed provided patient is already enrolled on ECOG-PACCT-1 and the treatment options in the other study are consistent with PACCT-1-specified treatment assignment (i.e., chemohormonal therapy or hormonal therapy alone)

Patient Characteristics:

• Female only
• Any menopausal status allowed
• WBC count ≥ 3,500/mm³
• Platelet count ≥ 100,000/mm³
• Creatinine ≤ 1.5 mg/dL
• AST ≤ 3 times upper limit of normal
• Life expectancy ≥ 10 years
• No chronic obstructive pulmonary disease requiring treatment
• No chronic liver disease (e.g., cirrhosis or chronic active hepatitis)
• No history of cerebrovascular accident
• No history of congestive heart failure or other cardiac disease that would contradict the use of an anthracycline (e.g., doxorubicin hydrochloride or epirubicin)
• No chronic psychiatric condition or other condition that would preclude study compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective nonhormonal contraception (e.g., intrauterine device, condoms, diaphragm, abstinence)
• No other invasive malignancies within the past 5 years except curatively treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix

Expected Enrollment

A total of 10,046 patients will be accrued for this study.

Outcomes

Disease-free survival
Distant recurrence-free interval
Recurrence-free interval
Overall survival

Outline

This is a multicenter, partially randomized study. Patients are assigned to 1 of 3 treatment groups based on their risk of distant recurrence determined by Oncotype DX Breast Cancer Assay.

• Group 1 (Secondary study group 1; Oncotype DX recurrence score [ODRS] < 11): Patients receive standard hormonal therapy (e.g., oral tamoxifen alone, oral aromatase inhibitor [e.g., anastrozole, letrozole, or exemestane] alone, or oral tamoxifen followed by oral aromatase inhibitor) at the discretion of the treating physician for 5 or 10 years.



• Group 2 (Primary study group; ODRS 11-25): Patients are stratified according to tumor size (≤ 2.0 cm vs ≥ 2.1 cm), menopausal status (postmenopausal vs premenopausal vs perimenopausal), planned chemotherapy (taxane-containing [i.e., paclitaxel, docetaxel] vs nontaxane-containing), and planned radiotherapy (whole breast with no boost planned vs whole breast with boost planned vs partial breast irradiation planned vs no planned radiation therapy [for patients who have had a mastectomy]). Patients are then randomized to receive either hormonal therapy alone or combination chemotherapy and hormonal therapy.
  • Arm I (experimental): Patients receive hormonal therapy as in group 1 at the discretion of the treating physician.
  
  
  
  • Arm II (standard): Patients receive standard combination chemotherapy at the discretion of the treating physician. Within 4 weeks after the last dose of chemotherapy, patients receive hormonal therapy as in group 1 at the discretion of the treating physician.
  
  
  



• Group 3 (Secondary study group 2; ODRS > 25): Patients receive combination chemotherapy as in group 2, arm II followed by hormonal therapy as in group 1.

Patients in all groups who have had breast-conservation surgery are also treated with radiotherapy. Radiotherapy should begin within 4 weeks of registration for patients receiving hormonal therapy alone or within 8 weeks after completion of chemotherapy. Patients participating in NSABP and/or RTOG partial irradiation trial(s) may receive partial breast radiation.

Tissue obtained at surgery (performed prior to study entry) is examined by the Oncotype DX Recurrence Score Assay and other assays to correlate response with various biomarkers.

After completion of study treatment, patients are followed periodically for up to 20 years.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Joseph Sparano, MD, Protocol chair		Ph: 718-920-4826 Email: jsparano@montefiore.org

Southwest Oncology Group

Daniel Hayes, MD, Protocol chair		Ph: 734-615-6725; 800-865-1125 Email: hayesdf@umich.edu

Cancer and Leukemia Group B

Elizabeth Dees, MD, Protocol chair		Ph: 919-966-4431

American College of Surgeons Oncology Group

John Olson, MD, PhD, Protocol chair		Ph: 919-668-1767 Email: jaomd@duke.edu

North Central Cancer Treatment Group

Edith Perez, MD, Protocol chair		Ph: 507-284-1159 Email: perez.edith@mayo.edu

NCIC-Clinical Trials Group

Kathleen Pritchard, MD, Protocol chair		Ph: 416-480-4616 Email: kathy.pritchard@sunnybrook.ca

National Surgical Adjuvant Breast and Bowel Project

Charles Geyer, FACP, MD, Protocol chair		Ph: 412-359-8353; 866-680-0004

U.S.A.
Alabama
	Anniston
	Regional Medical Center
		Ellen Spremulli	Ph:  256-235-5877
	Birmingham
	Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
		Clinical Trials Office - Lurleen Wallace Comprehensive Cancer	Ph:  205-934-0309
Alaska
	Fairbanks
	Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital
		Jacqueline Vuky	Ph:  907-458-5380 800-678-5458
Arkansas
	Ft. Smith
	Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
		John Wells, MD	Ph:  479-484-4700
	Hot Springs
	St. Joseph's Mercy Cancer Center
		Prabhakara Reddy	Ph:  501-623-2731
	Little Rock
	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
		Clinical Trial Office - Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Ph:  501-686-8274
California
	Arroyo Grande
	Arroyo Grande Community Hospital
		David Palchak, MD	Ph:  805-773-7127
	Berkeley
	Alta Bates Summit Comprehensive Cancer Center
		Clinical Trials Office - Alta Bates Summit Comprehensive Cancer Center	Ph:  510-204-3428
	Burbank
	Providence Saint Joseph Medical Center - Burbank
		Clinical Trials Office - Providence Saint Joseph Medical Center - Burbank	Ph:  818-847-3220
	Burlingame
	Peninsula Medical Center
		David Irwin, MD	Ph:  510-204-1591
	Castro Valley
	Valley Medical Oncology Consultants - Castro Valley
		James Feusner, MD	Ph:  510-428-3689
	Chico
	Enloe Cancer Center at Enloe Medical Center
		Clinical Trials Office - Enloe Cancer Center at Enloe Medical Center	Ph:  530-332-3808
	Concord
	Cancer Care Center at John Muir Health - Concord Campus
		Clinical Trials Office - Cancer Care Center at John Muir Health - Concord Campus	Ph:  925-674-2580
	Duarte
	City of Hope Comprehensive Cancer Center
		Clinical Trials Office - City of Hope Comprehensive Cancer Center	Ph:  800-826-4673
			Email: becomingapatient@coh.org
	Fairfield
	North Bay Cancer Center
		Clinical Trials Office - North Bay Cancer Center	Ph:  707-429-6976
	Fremont
	Kaiser Permanente - Fremont
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Valley Medical Oncology
		James Feusner, MD	Ph:  510-428-3689
	Washington Township Hospital
		Byron Wilson, MD	Ph:  510-888-0657
	Fresno
	California Cancer Center - Woodward Park Office
		Dina Ibrahim	Ph:  559-451-3647
	Glendale
	Glendale Memorial Hospital Comprehensive Cancer Center
		Clinical Trials Office - Glendale Memorial Hospital Comprehensive Cancer Center	Ph:  818-409-7653
	Greenbrae
	Sutter Health - Western Division Cancer Research Group
		David Irwin, MD	Ph:  510-204-1591
	Hayward
	Kaiser Permanente Medical Center - Hayward
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	La Jolla
	Rebecca and John Moores UCSD Cancer Center
		Clinical Trials Office - Rebecca and John Moores UCSD Cancer Center	Ph:  858-822-5354
			Email: cancercto@ucsd.edu
	Scripps Cancer Center - San Diego
		Joan Kroener, MD	Ph:  858-554-8629
	Los Angeles
	Jonsson Comprehensive Cancer Center at UCLA
		Clinical Trials Office - Jonsson Comprehensive Cancer Center at UCLA	Ph:  888-798-0719
	USC/Norris Comprehensive Cancer Center and Hospital
		Clinical Trials Office - USC/Norris Comprehensive Cancer Center and Hospital	Ph:  323-865-0451
	Martinez
	Contra Costa Regional Medical Center
		James Feusner, MD	Ph:  510-428-3689
	Marysville
	Tibotec Therapeutics - Division of Ortho Biotech Products, LP
		Helen Chew, MD	Ph:  916-734-3771
	Modesto
	Memorial Medical Center
		Clinical Trials Office - Memorial Medical Center	Ph:  209-572-7116
	Monterey
	Community Hospital of the Monterey Peninsula Comprehensive Cancer Center
		Thomas Bradley, MD, PhD, FACP	Ph:  831-375-4777
	Northridge
	Leavey Cancer Center at Northridge Hospital Medical Center
		Clinical Trials Office - Leavey Cancer Center	Ph:  818-885-5458
	Oakland
	Alta Bates Summit Medical Center - Summit Campus
		Clinical Trials Office - Alta Bates Summit Medical Center - Summit Campus	Ph:  510-204-1414
	CCOP - Bay Area Tumor Institute
		James Feusner, MD	Ph:  510-428-3689
	Highland General Hospital
		James Feusner, MD	Ph:  510-428-3689
	Kaiser Permanente Medical Center - Oakland
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Orange
	St. Joseph Hospital Regional Cancer Center - Orange
		Tiberio Lindgren	Ph:  714-771-8999
	Pleasanton
	Valley Care Medical Center
		James Feusner, MD	Ph:  510-428-3689
	Valley Medical Oncology Consultants - Pleasanton
		James Feusner, MD	Ph:  510-428-3689
	Pomona
	Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center
		Clinical Trials Office - Robert and Beverly Lewis Family Cancer Care Center	Ph:  909-865-9555
	Redding
	Mercy Regional Cancer Center at Mercy Medical Center
		Clinical Trials Office - Mercy Regional Cancer Center	Ph:  530-225-7471
	Redwood City
	Kaiser Permanente Medical Center - Redwood City
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Richmond
	Kaiser Permanente Medical Center - Richmond
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Roseville
	Kaiser Permanente Medical Center - Roseville
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Sacramento
	Kaiser Permanente Medical Center - Sacramento
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Mercy General Hospital
		Colin Spears, MD	Ph:  916-736-1536
	South Sacramento Kaiser-Permanente Medical Center
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Sutter Cancer Center
		Clinical Trial Office - Sutter Cancer Center	Ph:  916-454-6595
	Salinas
	Salinas Valley Memorial Hospital
		Shehzad Aziz, MD	Ph:  831-755-1701
	San Diego
	Kaiser Permanente Medical Office -Vandever Medical Office
		Jonathan Polikoff, MD	Ph:  619-528-5888
	Sharp Memorial Hospital Cancer Center
		Clinical Trials Office - Sharp Memorial Hospital Cancer Center	Ph:  858-939-5015
	San Francisco
	California Pacific Medical Center - California Campus
		David Irwin, MD	Ph:  510-204-1591
	Kaiser Permanente Medical Center - San Francisco Geary Campus
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	San Jose
	Kaiser Permanente Medical Center - Santa Teresa
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	San Pablo
	Doctors Medical Center - San Pablo Campus
		James Feusner, MD	Ph:  510-428-3689
	San Rafael
	Kaiser Foundation Hospital - San Rafael
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Santa Clara
	Kaiser Permanente Medical Center - Santa Clara Kiely Campus
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Santa Rosa
	Kaiser Permanente Medical Center - Santa Rosa
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	South San Francisco
	Kaiser Permanente Medical Center - South San Francisco
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Stockton
	Kaiser Permanente Medical Facility - Stockton
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Vallejo
	Kaiser Permanente Medical Center - Vallejo
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Sutter Solano Medical Center
		David Irwin, MD	Ph:  510-204-1591
	Walnut Creek
	John Muir/Mt. Diablo Comprehensive Cancer Center
		Clinical Trials Office - John Muir/Mt. Diablo Comprehensive Cancer Center	Ph:  925-941-4246
	Kaiser Permanente Medical Center - Walnut Creek
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Whittier
	Ruby L. Golleher Cancer Program at Presbyterian Intercommunity Hospital
		Jack Freimann, MD	Ph:  562-945-6770
Colorado
	Aurora
	University of Colorado Cancer Center at UC Health Sciences Center
		Clinical Trials Office - University of Colorado Cancer Center	Ph:  720-848-0650
	Boulder
	Boulder Community Hospital
		Clinical Trials Office - Boulder Community Hospital	Ph:  303-938-5253
	Colorado Springs
	Memorial Hospital Cancer Center - Colorado Springs
		Clinical Trials Office - Memorial Hospital	Ph:  719-365-2406
	Penrose Cancer Center at Penrose Hospital
		Clinical Trials Office - Penrose Cancer Center	Ph:  719-776-5275
	Denver
	CCOP - Colorado Cancer Research Program
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	St. Joseph Hospital
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Grand Junction
	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Greeley
	North Colorado Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Longmont
	Hope Cancer Care Center at Longmont United Hospital
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Montrose
	Montrose Memorial Hospital Cancer Center
		Clinical Trials Office - Montrose Memorial Hospital Cancer Center	Ph:  670-240-7267
	Wheat Ridge
	Exempla Lutheran Medical Center
		Clinical Trials Office - Exempla Lutheran Medical Center	Ph:  303-403-3605
Connecticut
	Bridgeport
	Bridgeport Hospital
		Clinical Trials Office - Bridgeport Hospital	Ph:  203-384-4869
	St. Vincent's Medical Center
		Anthy Demestihas	Ph:  203-576-6000
	Danbury
	Praxair Cancer Center at Danbury Hospital
		Robert Cooper, MD