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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Southwest Oncology Group
American College of Surgeons
North Central Cancer Treatment Group
Cancer and Leukemia Group B
National Surgical Adjuvant Breast and Bowel Project (NSABP)
NCIC Clinical Trials Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00310180
First received: March 29, 2006
Last updated: July 22, 2014
Last verified: June 2014
  Purpose

This randomized phase III trial studies 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. 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, by stopping them from dividing, or by stopping them from spreading. 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.


Condition Intervention Phase
Estrogen Receptor-positive Breast Cancer
HER2-negative Breast Cancer
Progesterone Receptor-positive Breast Cancer
Stage IA Breast Cancer
Stage IB Breast Cancer
Stage IIA Breast Cancer
Stage IIB Breast Cancer
Stage IIIB Breast Cancer
Drug: tamoxifen citrate
Drug: anastrozole
Drug: letrozole
Drug: exemestane
Radiation: radiation therapy
Other: laboratory biomarker analysis
Other: quality-of-life assessment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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:


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

Primary Outcome Measures:
  • Disease-free survival [ Time Frame: Date of randomization or registration to the date of ipsilateral breast tumor recurrence, local/regional recurrence, distant recurrence, second primary cancer (breast or non-breast), or death from any cause, assessed up to 10 years ] [ Designated as safety issue: No ]
    DFS will be compared using a stratified log rank test.


Secondary Outcome Measures:
  • Distant recurrence-free interval [ Time Frame: Date of randomization or registration to the date of distant recurrence of breast cancer, or of death with distant recurrence, if death is the first manifestation of distant recurrence, assessed up to 10 years ] [ Designated as safety issue: No ]
    Compared using a stratified log rank test.

  • Recurrence-free interval [ Time Frame: Date of randomization or registration to the date of first recurrence of breast cancer (IBTR, LRR, or DR) or to the date of death with recurrence, if death is the first manifestation of recurrence, assessed up to 20 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Date of randomization or registration to date of death from any cause, assessed up to 20 years ] [ Designated as safety issue: No ]
  • Perceived cognitive function evaluated using the Functional Assessment of Cancer Therapy - Cognitive Function (FACT-COG) version 3 [ Time Frame: At 3 months ] [ Designated as safety issue: No ]
    A t-test comparing the 3-month evaluations will have 90% power for a mean difference of 4.5 points (0.3 standard deviations), allowing a two-sided type I error of 5%. Within the postmenopausal and premenopausal subsets, there will be 90% power to detect a mean difference of 5.7 and 7.35 points (0.38 and 0.49 standard deviations), respectively.

  • Quality of life measured using FACT-COG, fatigue (FACT-Fatigue and Patient Reported Outcomes Measurement Information System Fatigue SF), fear of recurrence (Assessment of Survivor Concerns), endocrine symptoms (FACT-ES) and HRQL (FACT-General) [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]
    Simultaneous confidence intervals for differences over time will be determined from a model where the effects are allowed to vary smoothly over time which gives a reasonable fit to the data. The relationship of cognitive function to outcomes in other domains, such as symptoms of depression and anxiety (assessed by the Hospital Anxiety and Depression Scale) and fatigue (assessed by the FACT fatigue scale) will be evaluated by including the values as (time-dependent) covariates in the longitudinal models.


Estimated Enrollment: 11248
Study Start Date: April 2006
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1 (Oncotype DX recurrence score =< 10)
Patients in this group receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years.
Drug: tamoxifen citrate
Given PO
Other Names:
  • Nolvadex
  • TAM
  • tamoxifen
  • TMX
Drug: anastrozole
Given PO
Other Names:
  • ANAS
  • Arimidex
  • ICI-D1033
Drug: letrozole
Given PO
Other Names:
  • CGS 20267
  • Femara
  • LTZ
Drug: exemestane
Given PO
Other Names:
  • Aromasin
  • FCE-24304
  • PNU 155971
Radiation: radiation therapy
Undergo radiation therapy or partial breast irradiation
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Group 2, Arm I (experimental)
Patients receive hormonal therapy as in Group 1 at the discretion of the treating physician.
Drug: tamoxifen citrate
Given PO
Other Names:
  • Nolvadex
  • TAM
  • tamoxifen
  • TMX
Drug: anastrozole
Given PO
Other Names:
  • ANAS
  • Arimidex
  • ICI-D1033
Drug: letrozole
Given PO
Other Names:
  • CGS 20267
  • Femara
  • LTZ
Drug: exemestane
Given PO
Other Names:
  • Aromasin
  • FCE-24304
  • PNU 155971
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Active Comparator: Group 2, 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.
Drug: tamoxifen citrate
Given PO
Other Names:
  • Nolvadex
  • TAM
  • tamoxifen
  • TMX
Drug: anastrozole
Given PO
Other Names:
  • ANAS
  • Arimidex
  • ICI-D1033
Drug: letrozole
Given PO
Other Names:
  • CGS 20267
  • Femara
  • LTZ
Drug: exemestane
Given PO
Other Names:
  • Aromasin
  • FCE-24304
  • PNU 155971
Radiation: radiation therapy
Undergo radiation therapy or partial breast irradiation
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Group 3 (Oncotype DX recurrence score >= 26)
Patients in this group receive combination chemotherapy followed by hormone therapy similar to the patients in group two who are assigned to receive both types of treatment.
Drug: tamoxifen citrate
Given PO
Other Names:
  • Nolvadex
  • TAM
  • tamoxifen
  • TMX
Drug: anastrozole
Given PO
Other Names:
  • ANAS
  • Arimidex
  • ICI-D1033
Drug: letrozole
Given PO
Other Names:
  • CGS 20267
  • Femara
  • LTZ
Drug: exemestane
Given PO
Other Names:
  • Aromasin
  • FCE-24304
  • PNU 155971
Radiation: radiation therapy
Undergo radiation therapy or partial breast irradiation
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • Patients with operable histologically confirmed adenocarcinoma of the female breast who have completed primary surgical treatment and meet the following criteria:

    • ER and/or progesterone receptor (PR)-positive: Estrogen and/or progesterone receptor positive disease (as defined by local pathology laboratory)
    • Negative axillary nodes: As assessed by a sentinel lymph node biopsy, an axillary dissection, or both, and as defined by the Sixth Edition of the American Joint Committee on Cancer (AJCC) staging criteria
    • Tumor size 1.1-5.0 cm (or 5 mm-1.0 cm plus unfavorable histological features):

      • Unfavorable features defined as intermediate or poor nuclear and/or histologic grade, or lymphovascular invasion
      • NOTE: Definition of tumor size: The tumor size used for determination of eligibility is the pathologic tumor size, which is usually determined by the size of the tumor as measured by inspection of the gross specimen; if the tumor size is measured microscopically and the tumor includes ductal carcinoma in-situ, the measurement should include only the invasive component of the tumor
    • The tumor must be human epidermal growth factor receptor 2 (Her2)/neu negative by either fluorescent in-situ hybridization (FISH) or immunohistochemistry (e.g. 0 or 1+ by DAKO Herceptest)
  • The patient and physician must be agreeable to initiate standard chemotherapy and hormonal therapy as adjuvant therapy
  • A tissue specimen from the primary breast cancer has been located and is ready to be shipped to the appropriate laboratory after consent is obtained and within 3 days following pre-registration; NOTE: For determination of the Oncotype Recurrence Score, tissue must be shipped to Genomic Health; if the Oncotype DX Recurrence Score was previously performed by Genomic Health (prior to pre-registration), tissue must be submitted to the Eastern Cooperative Oncology Group (ECOG)-American College of Radiology Imaging Network (ACRIN) Pathology Coordinating Office upon randomization
  • Leukocyte count >= 3500/mm^3
  • Platelets >= 100,000/mm^3
  • Serum creatinine =< 1.5 mg/dL
  • Serum aspartate transaminase (AST) that is =< 3-fold the upper institutional limits of normal
  • Patients must be disease-free of prior invasive malignancies for >= 5 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix; patients with a previous ipsilateral or contralateral invasive breast cancer, or with bilateral synchronous cancers, are not eligible; patients with previous ipsilateral or contralateral ductal in situ carcinoma (DCIS) are not eligible
  • Prior treatment

    • Mandatory prior surgery criteria:

      • Patient must pre-register within 84 days from the final surgical procedure required to adequately treat the primary tumor (please note that if margins are not clear and a resection has to be conducted after pre-registration but before randomization, the patient will be deemed to be within the 84 day window allowed by protocol and therefore eligible)
      • All tumors should be removed by either a mastectomy or local excision plus an acceptable axillary procedure (i.e., sentinel lymph node biopsy, axillary dissection, or both); there must be adequate (at least 1 mm if margin width specified) tumor-free margins of resection (for invasive and ductal carcinoma in-situ) in order for the patients to be eligible; patients with lobular carcinoma in-situ involving the resection margins are eligible
    • Criteria re: other prior treatments:

      • No prior chemotherapy for this malignancy
      • No prior radiation therapy for this malignancy; this includes no prior MammoSite Brachytherapy radiation therapy (RT)
      • Hormonal therapy: Patients who develop breast cancer while receiving a selective estrogen-receptor modulator (SERM; e.g., tamoxifen, toremifene, raloxifene) or an aromatase inhibitor (e.g., anastrazole, letrozole, exemestane) for breast cancer prevention or a SERM for other indications (e.g., raloxifene for osteoporosis) are not eligible; however, patients may have received up to 8 weeks of a SERM or aromatase inhibitor for this malignancy and still be eligible for study entry
  • Patients must have an anticipated life expectancy of at least 10 years
  • Patients with the following medical conditions should not be enrolled on the study:

    • Chronic obstructive pulmonary disease requiring treatment
    • Chronic liver disease (e.g., cirrhosis, chronic active hepatitis)
    • Previous history of a cerebrovascular accident
    • History of congestive heart failure or other cardiac disease that would represent a contraindication to the use of an anthracycline (e.g., doxorubicin or epirubicin)
    • Chronic psychiatric condition or other condition that would impair compliance with the treatment regimen
  • Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to pre-registration to rule out pregnancy

    • Women of childbearing potential must be strongly advised to utilize an accepted and effective form of non-hormonal contraception (e.g. intrauterine device, condoms, diaphragm, abstinence)
  • Patients must not have previously had the Oncotype DX Assay performed, with the exception of patients who have had the assay performed and have a recurrence score of 11-25
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 1185 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
American College of Surgeons
North Central Cancer Treatment Group
Cancer and Leukemia Group B
National Surgical Adjuvant Breast and Bowel Project (NSABP)
NCIC Clinical Trials Group
Investigators
Principal Investigator: Joseph Sparano ECOG-ACRIN Cancer Research Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00310180     History of Changes
Obsolete Identifiers: NCT00554931
Other Study ID Numbers: NCI-2009-00707, NCI-2009-00707, CDR0000472066, ECOG-PACCT-1, PACCT-1, PACCT-1, U10CA021115, U10CA180820
Study First Received: March 29, 2006
Last Updated: July 22, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Anastrozole
Exemestane
Letrozole
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Bone Density Conservation Agents
Estrogen Antagonists
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 26, 2014