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

Phase 2

Withdrawn

• Conditions: Estrogen Receptor-positive Breast Cancer; Breast Cancer
• Interventions: Drug: Aspirin; Drug: Tamoxifen Pill; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Paclitaxel

• Registration Number: NCT04038489
• Lead Sponsor: University of Virginia

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-07-10
• Study First Submitted QC: 2019-07-29
• Study First Posted: 2019-07-30
• Study Start: 2019-10-18
• Status Verified: 2021-11
• Last Update Submitted: 2021-11-12
• Last Update Posted: 2021-11-22
• Primary Completion: 2023-04-30
• Study Completion: 2023-04-30

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tamoxifen and Aspirin with AC-T Chemotherapy	Tamoxifen Pill	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.
Tamoxifen and Aspirin with AC-T Chemotherapy	Aspirin	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.
Tamoxifen and Aspirin with AC-T Chemotherapy	Doxorubicin	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.
Tamoxifen and Aspirin with AC-T Chemotherapy	Cyclophosphamide	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.
Tamoxifen and Aspirin with AC-T Chemotherapy	Paclitaxel	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.

Primary Outcome Measures

Name	Time	Method
Adverse events (AEs)	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)	Frequency of adverse events occurring during and shortly after the study intervention
Pathologic complete response (pCR) rate	At the time of surgery, following completion of AC-T chemotherapy, usually about 7.5 months	Rate of participants that no longer have any tumor identified at the time of surgery after chemotherapy

Trial Locations

Locations (1)

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States