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

NCT ID: NCT04038489

Last Updated: 2021-11-22

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-18
• Study Completion Date: 2023-04-30

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Aspirin

Intervention Type: DRUG

325 mg aspirin daily during AC-T chemotherapy

Tamoxifen Pill

Intervention Type: DRUG

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

Doxorubicin

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

Paclitaxel

Intervention Type: DRUG

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

Interventions

Aspirin

325 mg aspirin daily during AC-T chemotherapy

Intervention Type: DRUG

Tamoxifen Pill

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

Intervention Type: DRUG

Doxorubicin

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

Intervention Type: DRUG

Cyclophosphamide

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

Intervention Type: DRUG

Paclitaxel

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

Intervention Type: DRUG

Other Intervention Names

Adriamycin; Cytoxan; Taxol

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Virginia

OTHER

Sponsor Role: lead

Responsible Party

Patrick Dillon, MD

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Patrick Dillon, MD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

University of Virginia

Charlottesville, Virginia, United States

Countries

United States

Other Identifiers

21822

Identifier Type: -

Identifier Source: org_study_id