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

Sponsor:	Eastern Cooperative Oncology Group
Collaborators:	National Cancer Institute (NCI) Southwest Oncology Group Cancer and Leukemia Group B American College of Surgeons North Central Cancer Treatment Group NCIC Clinical Trials Group National Surgical Adjuvant Breast and Bowel Project (NSABP)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00310180

Purpose

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy may fight breast cancer by blocking the use of estrogen by the tumor cells or by lowering the amount of estrogen the body makes. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving hormone therapy together with more than one chemotherapy drug (combination chemotherapy) has been shown to reduce the chance of breast cancer recurrence, but the benefit of adding chemotherapy to hormone therapy for women with node-negative, estrogen-receptor positive breast cancer is small. New tests may provide information about which patients are more likely to benefit from chemotherapy.

PURPOSE: This randomized phase III trial is trying to find out the best individual therapy for women who have node-negative, estrogen-receptor positive breast cancer by using a special test (Oncotype DX), and whether hormone therapy alone or hormone therapy together with combination chemotherapy is better for women who have an Oncotype DX recurrence score of 11-25.

Condition	Intervention	Phase
Breast Cancer	Drug: anastrozole Drug: chemotherapy Drug: exemestane Drug: letrozole Drug: tamoxifen citrate	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized
Official Title:	Program for the Assessment of Clinical Cancer Tests (PACCT-1): Trial Assigning Individualized Options for Treatment: The TAILORx Trial

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Surgery

Drug Information available for: Tamoxifen Tamoxifen citrate Exemestane Letrozole Anastrozole

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Disease-free survival [ Designated as safety issue: No ]
Distant recurrence-free interval [ Designated as safety issue: No ]
Recurrence-free interval [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]

Estimated Enrollment:	11248
Study Start Date:	April 2006
Estimated Primary Completion Date:	April 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group 1 (Oncotype DX recurrence score < 11): Experimental Patients in this group will receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane by mouth for up to 5 years. Some patients will then continue to receive hormone therapy for an additional 5 years.	Drug: anastrozole Given after chemotherapy or by mouth alone for up to 10 years Drug: exemestane Given after chemotherapy or by mouth alone for up to 10 years Drug: letrozole Given after chemotherapy or by mouth alone for up to 10 years Drug: tamoxifen citrate Given after chemotherapy or by mouth alone for up to 10 years
Group 2 (Oncotype DX recurrence score 11-25): Experimental Patients in this group will be randomly assigned to receive either hormone therapy alone or combination chemotherapy and hormone therapy.	Drug: anastrozole Given after chemotherapy or by mouth alone for up to 10 years Drug: chemotherapy Given prior to hormone therapy in some patients Drug: exemestane Given after chemotherapy or by mouth alone for up to 10 years Drug: letrozole Given after chemotherapy or by mouth alone for up to 10 years Drug: tamoxifen citrate Given after chemotherapy or by mouth alone for up to 10 years
Group 2, arm I (experimental): Experimental Patients receive hormonal therapy as in group 1 at the discretion of the treating physician.	Drug: anastrozole Given after chemotherapy or by mouth alone for up to 10 years Drug: exemestane Given after chemotherapy or by mouth alone for up to 10 years Drug: letrozole Given after chemotherapy or by mouth alone for up to 10 years Drug: tamoxifen citrate Given after chemotherapy or by mouth alone for up to 10 years
Group 2, arm II (standard): Active Comparator 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.	Drug: anastrozole Given after chemotherapy or by mouth alone for up to 10 years Drug: chemotherapy Given prior to hormone therapy in some patients Drug: exemestane Given after chemotherapy or by mouth alone for up to 10 years Drug: letrozole Given after chemotherapy or by mouth alone for up to 10 years Drug: tamoxifen citrate Given after chemotherapy or by mouth alone for up to 10 years
Group 3 (Oncotype DX recurrence score > 25): Experimental Patients in this group will receive combination chemotherapy followed by hormone therapy similar to the patients in group two who are assigned to receive both types of treatment.	Drug: anastrozole Given after chemotherapy or by mouth alone for up to 10 years Drug: chemotherapy Given prior to hormone therapy in some patients Drug: exemestane Given after chemotherapy or by mouth alone for up to 10 years Drug: letrozole Given after chemotherapy or by mouth alone for up to 10 years Drug: tamoxifen citrate Given after chemotherapy or by mouth alone for up to 10 years

Hide Detailed Description

Detailed Description:

OBJECTIVES:

Primary

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.
Compare the distant recurrence-free interval, recurrence-free interval, and overall survival of patients with an ODRS of 11-25 treated with these regimens.
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

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.
Determine the disease-free survival, distant recurrence-free interval, recurrence-free interval, and overall survival of patients with ODRS of ≤ 10.
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.
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).
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.

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), 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]) and Oncotype DX Recurrence Score (11-15 vs 16-20 vs 21-25). 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.

PROJECTED ACCRUAL: A total of 11,248 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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 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

PATIENT CHARACTERISTICS:

Female only
Any menopausal status allowed
WBC count ≥ 3,500/mm^3
Platelet count ≥ 100,000/mm^3
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

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00310180

Show 869 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Southwest Oncology Group

Cancer and Leukemia Group B

American College of Surgeons

North Central Cancer Treatment Group

NCIC Clinical Trials Group

National Surgical Adjuvant Breast and Bowel Project (NSABP)

Investigators

Study Chair:	Joseph A. Sparano, MD	Montefiore Medical Center
Study Chair:	Daniel F. Hayes, MD	University of Michigan Cancer Center
Study Chair:	Elizabeth C. Dees, MD	UNC Lineberger Comprehensive Cancer Center
Study Chair:	John A. Olson, MD, PhD	Duke University
Study Chair:	Edith A. Perez, MD	Mayo Clinic
Study Chair:	Kathleen I. Pritchard, MD	Edmond Odette Cancer Centre at Sunnybrook
Study Chair:	Charles E. Geyer, FACP, MD	Allegheny Cancer Center at Allegheny General Hospital

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Featured trial article This link exits the ClinicalTrials.gov site

Publications:

Zujewski JA, Kamin L. Trial assessing individualized options for treatment for breast cancer: the TAILORx trial. Future Oncol. 2008 Oct;4(5):603-10.

Responsible Party:	ECOG Group Chair's Office ( Robert L. Comis )
Study ID Numbers:	CDR0000472066, 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
Study First Received:	March 29, 2006
Last Updated:	November 25, 2009
ClinicalTrials.gov Identifier:	NCT00310180 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage I breast cancer
stage II breast cancer
stage IIIB breast cancer

Additional relevant MeSH terms:

Estrogen Antagonists
Anastrozole
Molecular Mechanisms of Pharmacological Action
Skin Diseases
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Hormone Antagonists
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Breast Neoplasms
Enzyme Inhibitors
Bone Density Conservation Agents

Letrozole
Selective Estrogen Receptor Modulators
Tamoxifen
Pharmacologic Actions
Estrogen Receptor Modulators
Neoplasms
Neoplasms by Site
Therapeutic Uses
Exemestane
Aromatase Inhibitors
Breast Diseases

ClinicalTrials.gov processed this record on November 27, 2009