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

NCT04038489 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 21822
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Cancer; Estrogen Receptor-positive Breast Cancer

Keywords

ER+/HER2- Breast Cancer

Outcome Measures

Primary Outcomes (2)

• 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)

Study Arms (1)

Tamoxifen and Aspirin with AC-T Chemotherapy

EXPERIMENTAL

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; Drug: Tamoxifen Pill; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Paclitaxel

Interventions

Aspirin DRUG

325 mg aspirin daily during AC-T chemotherapy

Tamoxifen and Aspirin with AC-T Chemotherapy

Tamoxifen Pill DRUG

Tamoxifen (either 20 mg daily or 10 mg twice a day) during AC-T chemotherapy

Tamoxifen and Aspirin with AC-T Chemotherapy

Doxorubicin DRUG

Doxorubicin (60 mg/m2) Given by IV with cyclophosphamide

Also known as: Adriamycin

Tamoxifen and Aspirin with AC-T Chemotherapy

Cyclophosphamide DRUG

Cyclophosphamide (600 mg/m2) Given by IV with doxorubicin

Also known as: Cytoxan

Tamoxifen and Aspirin with AC-T Chemotherapy

Paclitaxel DRUG

Paclitaxel 80 mg/m2 or 175 mg/m2 based on provider preference. Given by IV after completion of doxorubicin/cyclophosphamide therapy

Also known as: Taxol

Tamoxifen and Aspirin with AC-T Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 18 or older
• 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
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
• Life expectancy ≥ 6 months
• 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
• If genomic profiling has been performed (OncotypeDx, Mammaprint or other), then the score must be in a medium- or high-risk range.
• 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
• Ability to take oral medication

You may not qualify if:

• 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)
• Current use of anticoagulant (e.g. warfarin (Coumadin), heparin, direct oral anticoagulants (DOAC)) within 72 hours of registration
• Pregnancy or lactation
• Currently in prison
• Requirement for supplemental oxygen therapy
• Current active cancer other than breast cancer
• History of severe bleeding that, in the treating investigator's opinion, would put the patient at increased risk with daily 325 mg aspirin use
• Known allergic reactions to aspirin, tamoxifen, doxorubicin, cyclophosphamide, or paclitaxel
• Participants classified according to the New York Heart Association classification as having Class II - IV heart disease (section 12.2)
• History of thrombosis or cerebrovascular accident

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Aspirin; Tamoxifen; Doxorubicin; Cyclophosphamide; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Stilbenes; Benzylidene Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Study Officials

• Patrick Dillon, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: All participants will receive aspirin and tamoxifen with standard AC-T chemotherapy

Study Record Dates

• First Submitted: July 10, 2019
• First Posted: July 30, 2019
• Study Start: October 18, 2019
• Primary Completion: April 30, 2023
• Study Completion: April 30, 2023
• Last Updated: November 22, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)