Endocrine Therapy in Treating Patients With HER2 Negative, Low Risk Breast Cancer

An Investigator Initiated Registry of Simple Oral Therapy for Low Risk Breast Cancer (SOLR)

This pilot clinical trial studies how well endocrine therapy works in treating patients with HER2 negative, low risk breast cancer. Estrogen can cause the growth of breast cancer cells. Endocrine therapies such as aromatase inhibitors and selective estrogen receptor modulators may lessen the amount of estrogen made by the body.

Study Overview

• Status: Withdrawn
• Conditions: Stage 0 Breast Cancer; Invasive Breast Carcinoma; Stage IA Breast Cancer; HER2/Neu Negative; Postmenopausal
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Letrozole; Drug: Anastrozole; Drug: Exemestane; Drug: Tamoxifen Citrate; Drug: Toremifene Citrate

Detailed Description

PRIMARY OBJECTIVES:

I. To estimate the conversion rate from a standard low-toxicity approach to guideline-directed therapy which includes surgery +/- radiation therapy as a result of progression of disease or patient/provider choice.

II. To examine factors that might differ between those who convert from the low-toxicity approach to the guideline-directed therapy and those do not convert.

SECONDARY OBJECTIVES:

I. To measure the safety and clinical effectiveness of systemic endocrine therapy used in a prolonged neoadjuvant fashion.

II. To evaluate the impact of risk-stratified care in Quality-Adjusted Life Years (QALY) and QALY gains.

III. To estimate the cost savings of indefinitely delaying surgery and radiation in favor of systemic endocrine therapy alone.

OUTLINE:

Patients receive exemestane orally (PO) once daily (QD), anastrozole PO QD, letrozole PO QD, tamoxifen citrate PO QD, or toremifene citrate PO QD at the discretion of the treating physician. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Able to provide written informed consent

• A diagnosis of invasive breast cancer, with or without an in situ component, that is:

  • Originally identified by screening mammography
  • Characterized by standard diagnostic mammography +/- breast ultrasound
  • Clinically node negative
  • Confirmed by breast magnetic resonance imaging (MRI) in a facility that maintains active American College of Radiology (ACR) accreditation to be of low clinical stage (=< 2 cm, node negative, unifocal invasive)
  • Estrogen receptor (ER) and progesterone receptor (PR) Allred scored, each > 5/8
  • Her2 negative using American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guidelines
  • ki-67 proliferation scored, < 20%
  • Clinical Nottingham grade 1 or 2
  • Scored on the MammaPrint 70-gene breast cancer recurrence assay as low risk
• Prior to the discovery of the breast cancer, clinically post-menopausal as defined as: i) one or more years from last menses; or ii) history of oophorectomy; or iii) follicle stimulating hormone (FSH) test result in the post-menopause reference range
• Willing to accept oral endocrine therapy with a third generation aromatase inhibitor (AI) or selective estrogen receptor modifier (SERM)
• Willing to undergo routine surveillance with breast ultrasound and/or mammography

Exclusion Criteria:

• Known contraindication to aromatase inhibitor or SERM therapy
• Pregnant at time of or within prior year of diagnosis
• Clinically detected or palpable disease prior to biopsy in either breast or ipsilateral axilla
• Prior history of invasive breast cancer or ductal breast carcinoma in situ (DCIS)
• Prior use of aromatase inhibitor therapy apart from assisted reproduction
• Prior use of SERM
• Unmanaged/uncontrolled mental health disorder
• Life expectancy < 6 months (m) for any cause
• Biopsy confirmed multifocal, multicentric, or contralateral disease that is invasive or non-invasive
• DCIS with focal invasion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (AI, SERM); Patients receive exemestane PO QD, anastrozole PO QD, letrozole PO QD, tamoxifen citrate PO QD, or toremifene citrate PO QD at the discretion of the treating physician. Treatment continues in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Correlative studies; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Drug: Letrozole; Given PO; Other Names: CGS 20267; Femara; Drug: Anastrozole; Given PO; Other Names: Arimidex; Anastrazole; ICI D1033; ICI-D1033; ZD-1033; Drug: Exemestane; Given PO; Other Names: Aromasin; FCE-24304; Drug: Tamoxifen Citrate; Given PO; Other Names: Nolvadex; TAM; Soltamox; Apo-Tamox; Clonoxifen; Dignotamoxi; Ebefen; Emblon; Estroxyn; Fentamox; Gen-Tamoxifen; Genox; ICI 46,474; ICI-46474; Jenoxifen; Kessar; Ledertam; Lesporene; Nolgen; Noltam; Nolvadex-D; Nourytam; Novo-Tamoxifen; Novofen; Noxitem; Oestrifen; Oncotam; PMS-Tamoxifen; Tamax; Tamaxin; Tamifen; Tamizam; Tamofen; Tamoxasta; Tamoxifeni Citras; Zemide; Drug: Toremifene Citrate; Given PO; Other Names: Acapodene; Fareston; FC-1157a; GTx-006

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conversion from oral endocrine therapy for any reason to guideline-directed therapy	Includes clinical or radiographic progression, patient preference, endocrine therapy intolerance or toxicity, or death from any cause. Descriptive statistics will be summarized among all patients and patients within each of the two groups (stay with oral therapy vs conversion due to any causes).	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Advanced imaging (if performed on any subset of patients)	Will be compared to a concurrent group of patients managed in the conventional manner with upfront surgery +/- radiation therapy followed by systemic endocrine therapy. Descriptive statistics will be summarized among all patients and patients within each of the two groups (stay with oral therapy vs conversion due to any causes).	Up to 5 years
Cost-effectiveness and patient-centeredness outcomes defined as financial toxicity and solubility, quality of life (physical, mental, emotional changes) on endocrine therapy, and, access to support services	Comparisons will be made to historical benchmarks for similar patients managed in a conventional locoregional manner for early-stage breast cancer. Descriptive statistics will be summarized among all patients and patients within each of the two groups (stay with oral therapy vs conversion due to any causes).	Up to 5 years
Effect of age	Will be compared to a concurrent group of patients managed in the conventional manner with upfront surgery +/- radiation therapy followed by systemic endocrine therapy. Descriptive statistics will be summarized among all patients and patients within each of the two groups (stay with oral therapy vs conversion due to any causes).	Up to 5 years
Effect of comorbidity severity interaction	Will be compared to a concurrent group of patients managed in the conventional manner with upfront surgery +/- radiation therapy followed by systemic endocrine therapy. Descriptive statistics will be summarized among all patients and patients within each of the two groups (stay with oral therapy vs conversion due to any causes).	Up to 5 years
Effect of type of endocrine therapy type (selective estrogen receptor modifier versus aromatase inhibitor)	Will be compared to a concurrent group of patients managed in the conventional manner with upfront surgery +/- radiation therapy followed by systemic endocrine therapy. Descriptive statistics will be summarized among all patients and patients within each of the two groups (stay with oral therapy vs conversion due to any causes).	Up to 5 years
Effects emanating from tertiary care	Will be compared to a concurrent group of patients managed in the conventional manner with upfront surgery +/- radiation therapy followed by systemic endocrine therapy. Descriptive statistics will be summarized among all patients and patients within each of the two groups (stay with oral therapy vs conversion due to any causes).	Up to 5 years
Progression of disease while on primary endocrine therapy, as measured objectively by routine diagnostic breast imaging (mammography and/or ultrasound)	Descriptive statistics will be summarized among all patients and patients within each of the two groups (stay with oral therapy vs conversion due to any causes).	Up to 5 years

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Vijayakrishna Gadi, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2018
• Primary Completion (Anticipated): March 14, 2023
• Study Completion (Anticipated): March 14, 2025

Study Registration Dates

• First Submitted: July 31, 2017
• First Submitted That Met QC Criteria: July 31, 2017
• First Posted (Actual): August 3, 2017

Study Record Updates

• Last Update Posted (Actual): December 27, 2018
• Last Update Submitted That Met QC Criteria: December 26, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Breast Diseases; Carcinoma in Situ; Breast Neoplasms; Breast Carcinoma In Situ; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Anticoagulants; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Chelating Agents; Sequestering Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Calcium Chelating Agents; Letrozole; Tamoxifen; Anastrozole; Exemestane; Citric Acid; Sodium Citrate; Toremifene
• Other Study ID Numbers: 9764 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium); P30CA015704 (U.S. NIH Grant/Contract); NCI-2017-00724 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No