NCT01272037

Tamoxifen Citrate, Letrozole, Anastrozole, or Exemestane With or Without Chemotherapy in Treating Patients With Invasive RxPONDER Breast Cancer

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

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 5,018 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This randomized phase III clinical trial studies how well tamoxifen citrate, anastrozole, letrozole, or exemestane with or without chemotherapy work in treating patients with breast cancer that has spread from where it began in the breast to surrounding normal tissue (invasive). 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, by stopping them from dividing, or by stopping them from spreading. 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 OBJECTIVE: 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 molecular assays or test other signatures that measure prognosis and 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 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). XI. The presence of circulating tumor cells (CTC+) using two CTC platforms will be assessed at up to two time points to assess late recurrence in those still at risk for the primary outcome. XII. To compare clinically reported menopausal status with status categorized by serum hormone levels determined from baseline serum in women under age 55 years and to assess subsequent association with outcomes. BANKING OBJECTIVE: I. To bank specimens for future correlative studies. 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.

Conditions

• Breast Ductal Carcinoma In Situ
• Invasive Breast Carcinoma
• Multicentric Breast Carcinoma
• Multifocal Breast Carcinoma
• Synchronous Bilateral Breast Carcinoma

Interventions

Type	Name	Description
DRUG	Anastrozole	Given PO
DRUG	Exemestane	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Letrozole	Given PO
OTHER	Quality-of-Life Assessment	Ancillary studies (closed as of 12/1/12)
DRUG	Systemic Chemotherapy	Given IV
DRUG	Tamoxifen Citrate	Given PO

Timeline

• Start date: 2011-02-28
• Primary completion: 2023-02-01
• Completion: 2027-01-08
• First posted: 2011-01-07
• Last updated: 2026-04-13
• Results posted: 2023-06-27

Locations

1,572 sites across 10 countries: United States, Canada, Colombia, France, Ireland, Mexico, Puerto Rico, Saudi Arabia, South Korea, Spain