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

Breast Cancer Clinical Trial

— Breast 51  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04038489
• Other study ID #: 21822
• Status: Withdrawn
• Phase: Phase 2
• Start date: October 18, 2019
• Est. completion date: April 30, 2023

Study information

• Verified date: November 2021
• Source: University of Virginia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 30, 2023
• Est. primary completion date: April 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Estrogen Receptor-positive Breast Cancer

Intervention

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

Locations

Country	Name	City	State
United States	University of Virginia	Charlottesville	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
University of Virginia

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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)