COX Inhibition and Biomarkers During Neoadjuvant Chemoendocrine Therapy for ER+, HER2- Stage I-III Breast Cancer (Breast 51)

COX Inhibition and Biomarkers of Response During Neoadjuvant Chemoendocrine Therapy for Estrogen Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Stage I-III Breast Cancer

This study is designed to assess the safety and clinical activity of tamoxifen and the COX inhibitor, aspirin, given in combination with standard AC-T chemotherapy (doxorubicin, cyclophosphamide, and paclitaxel) for the treatment of high-risk estrogen receptor (ER)+, human epidermal growth factor receptor 2 (HER2)- breast cancer. If successful, the study could improve long-term outcomes for a subpopulation of women with aggressive stage I-III ER+/HER2- breast cancer.

Study Overview

• Status: Withdrawn
• Conditions: Breast Cancer; Estrogen Receptor-positive Breast Cancer
• Intervention / Treatment: Drug: Aspirin; Drug: Tamoxifen Pill; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Paclitaxel

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female, aged 18 or older
4. Newly diagnosed with ER+/HER2- stage I-III breast cancer according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines and the 8th edition of the American Joint Committee on Cancer (AJCC); ER positive is defined as ≥ 1% positive nuclear staining
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
6. Life expectancy ≥ 6 months
7. Women of childbearing potential and men must agree to use adequate contraception (see section 5.4) prior to study entry and for at least 3 months following the last dose of tamoxifen
8. If genomic profiling has been performed (OncotypeDx, Mammaprint or other), then the score must be in a medium- or high-risk range.
9. Adequate Organ Function as described below. There are no requirements regarding recent transfusions Absolute Neutrophil Count ≥1000/mm3 Platelets ≥100,000/mm3 Hemoglobin ≥9 g/dL Serum Creatinine or Glomerular Filtration Rate (GFR) ≤ 1.5 x upper limit of normal (ULN) Bilirubin ≤ 1.5 x ULN (except in patients with Gilbert's disease, where bilirubin to 4x ULN or direct bilirubin ≤ ULN is allowed) Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x ULN Alkaline phosphatase ≤ 2.5 x ULN
10. Ability to take oral medication

Exclusion Criteria:

1. Receipt of any systemic treatment for the current diagnosis of breast cancer (breast biopsy, excisional biopsy, or other local therapy is acceptable as long as residual disease is present and is appropriate for systemic chemotherapy and additional curative intent resection)
2. Current use of anticoagulant (e.g. warfarin (Coumadin), heparin, direct oral anticoagulants (DOAC)) within 72 hours of registration
3. Pregnancy or lactation
4. Currently in prison
5. Requirement for supplemental oxygen therapy
6. Current active cancer other than breast cancer
7. History of severe bleeding that, in the treating investigator's opinion, would put the patient at increased risk with daily 325 mg aspirin use
8. Known allergic reactions to aspirin, tamoxifen, doxorubicin, cyclophosphamide, or paclitaxel
9. Participants classified according to the New York Heart Association classification as having Class II - IV heart disease (section 12.2)
10. History of thrombosis or cerebrovascular accident

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Tamoxifen and Aspirin with AC-T Chemotherapy; AC-T chemotherapy includes 4 cycles of doxorubicin and cyclophosphamide given every 2 or 3 weeks followed by either 12 weekly cycles of lower dose paclitaxel or 4 cycles of higher dose paclitaxel every 2 or 3 weeks. During this time, all participants would receive daily aspirin and daily tamoxifen. After the AC-T chemotherapy, participants will undergo standard of care surgery to remove any remaining tumor.

Drug: Aspirin; 325 mg aspirin daily during AC-T chemotherapy; Drug: Tamoxifen Pill; Tamoxifen (either 20 mg daily or 10 mg twice a day) during AC-T chemotherapy; Drug: Doxorubicin; Doxorubicin (60 mg/m2) Given by IV with cyclophosphamide; Other Names: Adriamycin; Drug: Cyclophosphamide; Cyclophosphamide (600 mg/m2) Given by IV with doxorubicin; Other Names: Cytoxan; Drug: Paclitaxel; Paclitaxel 80 mg/m2 or 175 mg/m2 based on provider preference. Given by IV after completion of doxorubicin/cyclophosphamide therapy; Other Names: Taxol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic complete response (pCR) rate	Rate of participants that no longer have any tumor identified at the time of surgery after chemotherapy	At the time of surgery, following completion of AC-T chemotherapy, usually about 7.5 months
Adverse events (AEs)	Frequency of adverse events occurring during and shortly after the study intervention	From time of informed consent through 30 days after completion of study intervention (for AEs) or 90 days after completion of study intervention (for Serious AEs)

Collaborators and Investigators

• Sponsor: University of Virginia

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 18, 2019
• Primary Completion (ANTICIPATED): April 30, 2023
• Study Completion (ANTICIPATED): April 30, 2023

Study Registration Dates

• First Submitted: July 10, 2019
• First Submitted That Met QC Criteria: July 29, 2019
• First Posted (ACTUAL): July 30, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 22, 2021
• Last Update Submitted That Met QC Criteria: November 12, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: ER+/HER2- Breast Cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Aspirin; Cyclophosphamide; Paclitaxel; Doxorubicin; Tamoxifen
• Other Study ID Numbers: 21822

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
• product manufactured in and exported from the U.S.: No