The purpose of this study is to determine the impact of pre-operative cryoablation, and immune checkpoint inhibition (ICI) on on 3-year Event Free Survival (EFS), in women with residual hormone receptor negative, HER2-negative ("triple negative") resectable breast cancer after taxane-based neoadjuvant chemotherapy.
The purpose of this study is to determine the impact of pre-operative cryoablation, immune checkpoint inhibition (ICI) on 3-year Event Free Survival (EFS), in women with triple negative breast cancer after taxane-based neoadjuvant chemotherapy. Our strategy combines two interventions: induced activation and maturation of dendritic cells and tumor-specific T cells by cross-presentation of tumor antigens via local destruction of tumor tissue by cryoablation. Second, we administer Pembrolizumab, an antibody that inhibits lymphocyte programmed death 1 (PD-1) receptors and interferes with PD-1 mediated T-cell regulatory signaling; and was recently US FDA approved as curative-intent standard-of-care treatment for triple negative breast cancer. Women with residual triple negative resectable breast cancer after neoadjuvant chemotherapy will be treated with tumor cryoablation and pre-operative immune checkpoint inhibition (ICI). Women undergoing either mastectomy or breast conserving surgery are eligible.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
51
Pembro will be administered 1-20 days before the cryoablation date per SOC and q3 weeks after surgery for 9 cycles per SOC.
US-guided core biopsy and cryoablation 7-10 days prior to surgery.
Standard-of-care definitive surgery.
Cedars Sinai Medical Center
Los Angeles, California, United States
Ohio State University Medical Center
Columbus, Ohio, United States
Providence Cancer Institute
Portland, Oregon, United States
UT Southwestern Medical Center
Dallas, Texas, United States
Event-Free Survival
* Time (in months) between randomization and first occurrence of progression of disease that precludes surgery * Time (in months) between randomization and first occurrence local or distant disease recurrence * Time (in months) between randomization and date of death attributable to any cause including breast cancer, non-breast cancer, or unknown cause
Time frame: 36 Months
Invasive Disease-Free Survival
* Time (in months) between randomization and ipsilateral invasive breast tumor recurrence (i.e. an invasive breast cancer involving the same breast parenchyma as the original primary lesion); or * Time (in months) between randomization and ipsilateral local-regional invasive breast cancer (i.e. an invasive breast cancer in the axilla, regional lymph nodes, chest wall and/or skin of the ipsilateral breast); or * Time (in months) between randomization and distant recurrence (i.e. evidence of breast cancer in any anatomic site - other than the two abovementioned sites - that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer); or * Time (in months) between randomization and contralateral invasive breast cancer; or * Time (in months) between randomization and second primary non-breast invasive cancer; or * Time (in months) between randomization and date of death
Time frame: 36 Months
Distant Disease-Free Survival
-Time (in months) between randomization and the date of the first occurrence of distant recurrence (i.e. evidence of breast cancer in any anatomic site - other than local regional sites - that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer)
Time frame: 36 Months
Overall Survival
-Time (in months) between randomization and death attributable to any cause. Patients who are alive, including lost to follow-up, at the time of the analysis will be censored at the last known alive date.
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ipilimumab 1mg/Kg IV is administered 1-5 days prior to cryoablation.
nivolumab 240mg IV flat dose is administered 1-5 days prior to cryoablation and 240mg IV every 2 weeks ± 3 days starting 3 (+/-1) weeks after surgery.
Time frame: 36 Months
Overall Safety
Number of related adverse events based on CTCAE v.5.0
Time frame: 36 Months