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
80
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
ACTIVE_NOT_RECRUITINGOhio State University Medical Center
Columbus, Ohio, United States
COMPLETEDProvidence Cancer Institute
Portland, Oregon, United States
ACTIVE_NOT_RECRUITINGEvent-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.
UT Southwestern Medical Center
Dallas, Texas, United States
RECRUITINGTime frame: 36 Months
Overall Safety
Number of related adverse events based on CTCAE v.5.0
Time frame: 36 Months