Clinical Trials /

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

NCT04038489

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: COX Inhibition and Biomarkers During Neoadjuvant Chemoendocrine Therapy for ER+, HER2- Stage I-III Breast Cancer
  • 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 IDs

  • ORG STUDY ID: CoxInhib
  • NCT ID: NCT04038489

Conditions

  • Breast Cancer
  • Estrogen Receptor-positive Breast Cancer

Interventions

DrugSynonymsArms
AspirinTamoxifen and Aspirin with AC-T Chemotherapy
Tamoxifen PillTamoxifen and Aspirin with AC-T Chemotherapy
DoxorubicinAdriamycinTamoxifen and Aspirin with AC-T Chemotherapy
CyclophosphamideCytoxanTamoxifen and Aspirin with AC-T Chemotherapy
PaclitaxelTaxolTamoxifen and Aspirin with AC-T Chemotherapy

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Tamoxifen and Aspirin with AC-T ChemotherapyExperimentalAC-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.
  • Aspirin
  • Tamoxifen Pill
  • Doxorubicin
  • Cyclophosphamide
  • Paclitaxel

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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathologic complete response (pCR) rate
Time Frame:At the time of surgery, following completion of AC-T chemotherapy, usually about 7.5 months
Safety Issue:
Description:Rate of participants that no longer have any tumor identified at the time of surgery after chemotherapy

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Virginia

Trial Keywords

  • ER+/HER2- Breast Cancer

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