Official Title
A Phase III, Randomized Clinical Trial of Standard Adjuvant Endocrine Therapy +/- Chemotherapy in Patients With 1-3 Positive Nodes, Hormone Receptor-Positive and HER2-Negative Breast Cancer With Recurrence Score (RS) of 25 or Less. RxPONDER: A Clinical Trial Rx for Positive Node, Endocrine Responsive Breast Cancer
Purpose
This phase III clinical trial is studying how well giving tamoxifen citrate, anastrozole, letrozole, or exemestane with or without chemotherapy works in treating patients with invasive breast cancer. Estrogen can cause the growth of breast cancer cells. Hormone therapy, using tamoxifen citrate, may fight breast cancer by blocking the use of estrogen by the tumor cells. Aromatase inhibitors, such as anastrozole, letrozole, and exemestane, may fight breast cancer 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. It is not yet known whether giving tamoxifen citrate, anastrozole, letrozole, or exemestane is more effective with combination chemotherapy in treating patients with breast cancer.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the effect of chemotherapy in patients with node positive breast cancer who do not have high recurrence scores (RS) by Oncotype DX.
SECONDARY OBJECTIVES:
I. To compare overall survival (OS), distant disease-free survival (DDFS) and local disease-free interval (LDFI) by receipt of chemotherapy or not and its interaction with RS.
II. To compare the toxicity across the treatment arms. III. To perform other assays or tests (in particular the prediction analysis of microarray [PAM50] risk of relapse score), as they are developed and validated that measure potential benefit of chemotherapy and compare them to Oncotype DX.
IV. To determine the impact of management with Oncotype DX on patient-reported anxiety (co-primary Health-Related Quality of Life [HRQL] outcome) prior to screening, after disclosure of test results, and during the randomized trial.
V. To determine the impact of Oncotype DX on the initial management cost of node-positive, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer.
VI. To compare patient-reported utilities (e.g., quality of life [QOL]) for those randomized to chemotherapy versus no chemotherapy.
VII. Using modeling and DFS information from the trial, to estimate the cost-effectiveness of management with Oncotype DX vs usual care.
VIII. To determine the role of other assays (e.g., PAM50) as predictors of DFS, DDFS, and LDFI for patients randomized to chemotherapy versus no chemotherapy.
IX. To determine the impact of treatment with chemotherapy versus no chemotherapy on patient-reported fatigue and cognitive concerns (secondary HRQL outcomes).
X. To determine the impact of management with Oncotype DX on patient-reported decision conflict, perceptions regarding Oncotype DX testing, and survivor concerns prior to screening, after disclosure of test results, and during the randomized trial (secondary HRQL outcomes).
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive a protocol-approved chemotherapy regimen based on the patient and/or physician preference. Patients then receive a protocol-approved adjuvant endocrine therapy comprising tamoxifen citrate, an aromatase inhibitor (anastrozole, letrozole, or exemestane), or both for 5-10 years in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive a protocol-approved endocrine therapy comprising tamoxifen citrate, an aromatase inhibitor (anastrozole, letrozole, or exemestane), or both for 5-10 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 4 years, and then yearly for 15 years.
Age Limit
18 years & older
Eligibility Criteria
Inclusion Criteria
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Patients must have a complete history and physical examination within 28 days prior to registration
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Patients must have a performance status of 0-2 by Zubrod criteria
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Patients must be able to receive taxane and/or anthracycline based chemotherapy
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Patients will have undergone axillary staging by sentinel node biopsy or axillary lymph nodes dissection (ALND) patients must have at least one, but no more than three known positive lymph nodes (pN1a, pN1b or pN1c) patients with micrometastases as the only nodal involvement (pN1mi) are not eligible patients with positive sentinel node are not required to undergo full axillary lymph node dissection this is at the discretion of the treating physician axillary node evaluation is to be performed per the standard of care at each institution
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Exclusion Criteria
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Patients who have begun chemotherapy or endocrine therapy for their breast cancer prior to registration
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Patients who require concurrent chronic treatment with systemic steroids (inhaled steroids are allowed) or other immunosuppressive agents
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Patients who have received an aromatase inhibitor (AI) or a selective estrogen receptor modulator (SERM) such as tamoxifen or raloxifene within 5 years prior to registration
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No other prior malignancy is allowed except for adequately treated basal cell (or squamous cell) skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for 5 years
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Keywords and/or Specific Medical Conditions
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Antineoplastic Agents, Hormonal
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Bone Density Conservation Agents
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Estrogen Receptor Modulators
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Hormones, Hormone Substitutes, and Hormone Antagonists
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Molecular Mechanisms of Pharmacological Action
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Physiological Effects of Drugs
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Selective Estrogen Receptor Modulators
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Sponsors
- National Cancer Institute (NCI)
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