Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Adenocarcinoma

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

This is a pilot study evaluating the safety and tolerability of pre-operative, single-dose ipilimumab and/or cryoablation in patients with early stage/resectable breast cancer.

OncCore Biopsy (+ Cryo) Date\*

* Pre- and post- cryo MRI
* Core biopsy x ≥3
* Cryoablation Optional pre-surgery MRI day prior or day of Mastectomy Date\* Safety assessment 30 (+/-10) days after surgery research bloods 30 (+/-10) days after surgery.\*

Cryoablation

Ipilimumab Appt. with Med Onc Ipilimumab administered Core Biopsy Date\*

* MRI
* Core biopsy x ≥3 Optional pre-surgery MRI biopsy prior or day of Mastectomy Date\* Safety assessment 2-3 weeks post-mastectomy (co-ordinated with off-study surgery follow-up appt if feasible) and then every 2-3 weeks thereafter until at least 12 weeks post ipilimumab date. # Research bloods 30 (+/-10) days after surgery.

Heather McArthur, MD, MPH

This study is being done to evaluate the safety of two strategies called "cryoablation" and "immune therapy" in women with curable early stage breast cancer. "Cryoablation" is a procedure performed by an expert doctor called a radiologist. The radiologist uses (magnetic resonance imaging (MRI) to insert a needle directly into a cancer. Very cold temperatures are then applied through the needle to kill the cancer cells. Some of the killed cancer cells will be broken into pieces that can be recognized by a person's immune system.

The "immune therapy" in this study is a drug called ipilimumab. Normally the immune system makes "T cells" that can kill cancer cells when turned on. The cancer-killing T cell activity is controlled by a molecule called CTLA4. Ipilimumab works by turning off CTLA4. Turning off CTLA4 allows the cancer-fighting T cells to remain active Ipilimumab is an antibody drug has been made in a laboratory for patient use and was recently approved by the United States Food and Drug Administration (FDA) for the treatment of patients with a type of skin cancer called melanoma. An antibody is a normal protein that the immune system uses to find and kill germs like bacteria and viruses. This study is being done because the researchers believe that when cryoablation is combined with immune therapy, a person's immune system can be trained to recognize that person's cancer. This may prevent that cancer from coming back in the future. In other words, it is hoped that by adding cryoablation with ipilimumab before the mastectomy, the body will remain cancer free long after the mastectomy is performed. The first step in determining whether cryoablation and immune therapy can be used to cure breast cancer is to evaluate the safety of each strategy alone and then in combination in a small group of patients.

Pre-Operative, Single-Dose Ipilimumab and/or Cryoablation in Early Stage/Resectable Breast Cancer

A Pilot Study of Pre-Operative, Single-Dose Ipilimumab and/or Cryoablation in Early Stage/Resectable Breast Cancer

of pre-operative ipilimumab administration and intratumoral cryoablation administered either alone or in combination in patients with early stage breast cancer. Safety will be evaluated for all treated subjects using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v4.0 (CTCAE).

If 5 of the 6 patients in study arm A and 5 of the 6 patients in study arm B are without an AE necessitating delay in surgery, we will enroll 6 additional patients into study arm C. If 5 or 6 of these 6 patients in study arm C are without an AE necessitating delay in surgery, the regimen will be considered safe/tolerable for further study. Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v4.0 (CTCAE).

exploratory correlative studies will be performed to evaluate anti-tumor and immunological response pre- and post-treatment in individuals. Comparisons with other study participants will also be conducted. Breast cancer tissue specimens, axillary lymph nodes specimens where available, and peripheral blood samples will be studied.

Memorial Sloan Kettering Cancer Center

Triple Negative Breast Neoplasms

Pembrolizumab

Immunomodulating Agents

Study drug plus "tumor boost" before standard of care treatment

The second dose of pembrolizumab will be given in conjunction with an RT boost, consisting of 8 Gy for 3 fractions.

RT Boost

Stephen Shiao, MD, PHD

This study is being done to assess the feasibility of pembrolizumab (study drug) combined with standard radiation to the tumor (tumor boost) before patients undergo standard treatment that can consist of one or more of the following: breast-conserving surgery, radiation to the entire breast/chest wall after surgery, and chemotherapy.

Study participants will receive two doses of the study drug intravenously (through the vein) before their planned breast surgery or chemotherapy. The study drug will be administered three weeks apart. At the time of the second dose, radiation to the tumor in the affected breast will be given. This type of radiation treatment is called a "tumor boost", which is a standard part of radiation therapy for breast cancer that may occur either before or after planned breast-conserving surgery. Patients will receive breast surgery or begin chemotherapy approximately six weeks after your first dose of the study drug.

With more than 1 million new cases diagnosed yearly worldwide, breast cancer is a global public health burden. Over the past decade, molecular subtyping of breast cancer has identified intrinsic subtypes that may be at enhanced risk for both local and distant recurrence. This study focuses on the immunogenicity of high-risk breast cancer subtypes that are likely to display a dense lymphocytic infiltration including including TNBC and HR+/HER2- tumors.

Immune build up via immune co-stimulatory molecules permits the ensuing immune response to strengthen and destroy cancer systemically. Thus, the effect of the anti-tumor immune response initiated by the radiation to an intact tumor by combination with checkpoint blockade is increased.

Pembrolizumab is an optimal immunotherapy agent to study, as this agent has recently been FDA approved for use in multiple tumor types. It is therefore ready to be tested for efficacy in other disease sites and in combination with other treatments.

Single Arm with Two Cohorts

1. Cohort 1: High-risk, ER-positive and HER2-negative breast cancer patients with primary tumors measuring at least 2cm
2. Cohort 2: TNBC patients with primary tumors measuring at least 2cm

Breast Cancer Study of Preoperative Pembrolizumab + Radiation

Preoperative Combination of Pembrolizumab and Radiation Therapy in Patients With Operable Breast Cancer

Feasibility of preoperative radiation and Pembrolizumab in newly diagnosed, non-metastatic patients with triple negative breast cancer.

An increase in the tumor-infiltrating lymphocyte score (TILs) as measured by Salgado criteria. An increase in TILs is an indicator of immune system engagement (range is 0-100 in percent), therefore increase indicates better outcome. A lead in with pembrolizumab alone followed by the combination of pembrolizumab with RT will allow for serial assessment of TILs. This will establish the contribution of RT to the immune response generated by pembrolizumab. The working group's consensus for Salgado criteria is that TILs may provide more biological relevant information when scored as a continuous variable. The percentage of stromal TILs is a semi quantitative parameter for this assessment (0%-100%). No formal recommendation for a clinically relevant TIL threshold(s) can be given at this stage. The consensus was that a valid methodology is currently more important than issues of thresholds for clinical use, which will be determined once a solid methodology is in place.

Treatment toxicities. Number of AEs attributed to Pembrolizumab (considered at least possibly related, probably related, or related).

Treatment toxicities. Number of immune-related AEs (irAEs).

Disease-free survival, as described from time from occurrence of surgery to time from first recurrence from or death from breast cancer

Absence of invasive disease in the breast and lymph nodes at the time of curative-intent surgery.

United States Department of Defense

Stephen Shiao

Associate Professor of Radiation Oncology and Medicine

From week 1 until week 19 for all AEs, and immune-related AEs (irAEs) up until 1 year post treatment, up to 14 months.

Single Arm with 2 Cohorts: Cohort 1: High-risk, ER-positive and HER2-negative breast cancer patients with primary tumors measuring at least 2cm; Cohort 2: TNBC patients with primary tumors measuring at least 2cm. All subjects receive study intervention: pembrolizumab (checkpoint inhibitor) with the second dose of pembrolizumab given in conjunction with an RT boost ("tumor boost"), consisting of 8 Gy for 3 fractions, before standard of care treatment.

Pembrolizumab With RT Boost

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Co-primary outcome for change in TILs is incomplete at the time of this results submission, as some TILs data not currently available. Current results for this outcome measure is reported according to current available data. Additional data may be reported at a later date.

Stephen Shiao, MD, PhD

Number of Patients Who do Not Necessitate a Delay in Standard of Care Treatment After Receiving the Investigational Combination of Preoperative Pembrolizumab and Radiation

Changes in Tumor Infiltrating Lymphocytes (TIL)

Pembrolizumab-related Adverse Events

Immune-related Adverse Events

Median survival estimates not applicable at this moment due to lack of events.

Invasive Disease-free Survival After Preoperative Radiation and Pembrolizumab

Single Arm with 2 Cohorts: Cohort: TNBC patients with primary tumors measuring at least 2cm. All subjects receive pembrolizumab with an RT boost, consisting of 8 Gy for 3 fractions, before standard of care treatment.

PembroRT - Cohort: TNBC

Single Arm with 2 Cohorts: Cohort: High-risk, ER-positive and HER2-negative breast cancer patients with primary tumors measuring at least 2cm. All subjects receive pembrolizumab with an RT boost, consisting of 8 Gy for 3 fractions, before standard of care treatment.

PembroRT - Cohort: HR+

The analysis population includes patients starting from Phase II so there are a total of 50 evaluable subjects (40 TNBC; 10 HR+).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pre-Operative, Single-Dose Ipilimumab and/or Cryoablation in Early Stage/Resectable Breast Cancer	NCT01502592	Breast Cancer Invasive Adenoc...	Cryoablation Ipilimumab	18 Years -	Memorial Sloan Kettering Cancer Center
Breast Cancer Study of Preoperative Pembrolizumab + Radiation	NCT03366844	Breast Cancer	Pembrolizumab RT Boost	18 Years -	Cedars-Sinai Medical Center
Breast Cancer Study of Preoperative Pembrolizumab + Radiation	NCT03366844	Breast Cancer	Pembrolizumab RT Boost	18 Years -	Cedars-Sinai Medical Center

Spots Global Cancer Trial Database for invasive adenocarcinoma of the breast