This phase I trial studies the side effects and best dose of chemokine modulation therapy when given together with standard chemotherapy given before surgery in treating patients with early stage triple negative breast cancer. Chemokines are molecules that are involved in a variety of immune and inflammatory responses. Chemokine modulation therapy, including celecoxib, recombinant interferon alfa-2b, and rintatolimod, may modify the immune response and tumor-related processes and may stop tumor cells from growing. Drugs used in standard chemotherapy, such as paclitaxel, doxorubicin, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemokine modulation therapy together with standard chemotherapy may work better than giving either therapy alone in treating patients with triple negative breast cancer.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04081389.
PRIMARY OBJECTIVES:
I. To examine the safety and tolerability profile of the combination of rintatolimod, celecoxib +/- interferon alpha-2b, when given as chemokine-modulating regimen (CKM) along with chemotherapy in the neoadjuvant setting in early stage triple negative breast cancer.
II. To identify the appropriate dose level of CKM and paclitaxel for future clinical exploration.
SECONDARY OBJECTIVES:
I. Evaluate the effect of neoadjuvant CKM + paclitaxel on pathological response and breast magnetic resonance imaging (MRI) response in early stage triple negative breast cancer patients.
II. Evaluate the overall and recurrence-free survival in early stage triple negative breast cancer patients that received neoadjuvant CKM + paclitaxel.
EXPLORATORY OBJECTIVES:
I. To evaluate longitudinal changes of blood biomarkers such as peripheral T-cell subsets, myeloid derived suppressor cells (MDSC), expression of chemokine and other immune genes, circulating immune mediators and correlate them with the clinical course post-surgery.
II. Comparison of response assessment criteria for a prospective analysis using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. and immune-related (ir)RECIST.
III. Evaluate changes in the intratumoral levels of biomarkers, such as, peripheral T-cell subsets, myeloid derived suppressor cells (MDSC), chemokines, and immune-regulatory factors (pre- versus [vs] post-CKM + paclitaxel treatment).
OUTLINE: This is a dose-escalation study of recombinant interferon alfa-2b.
Patients receive celecoxib orally (PO) twice daily (BID), recombinant interferon alfa-2b intravenously (IV) over 20 minutes (omitted in lowest dose level), and rintatolimod IV on days 1-3 of weeks 1-3, as well as paclitaxel IV over 1 hour once weekly on day 1. Treatment continues for a total of 12 weeks in the absence of disease progression or unacceptable toxicity. 1-3 weeks after last dose of paclitaxel, patients receive doxorubicin IV over 10 minutes and cyclophosphamide IV over 30 minutes. Treatment repeats every 2 weeks for 4 cycles in the absence of unacceptable toxicity. Patients with evidence of disease progression but still receiving clinical benefit may continue treatment per physician discretion.
After completion of study treatment, patients are followed up for 30 days.
Lead OrganizationRoswell Park Cancer Institute
Principal InvestigatorShipra Gandhi
