Peri-Operative Immune Checkpoint Inhibition and Cryoablation in Women With Triple-negative Breast Cancer

NCT03546686 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STU-2021-1043
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Breast Cancer

Keywords

Hormone Receptor Negative; Her2- Negative; Resectable Breast Cancer; breast cancer; immunotherapy; Ipilimumab; Nivolumab; Cryoablation

Outcome Measures

Primary Outcomes (1)

• 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

  36 Months

Secondary Outcomes (4)

• Invasive Disease-Free Survival

  36 Months

• Distant Disease-Free Survival

  36 Months

• Overall Survival

  36 Months

• Overall Safety

  36 Months

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Pembrolizumab + Core Biopsy/Cryoablation + Breast Surgery +Post Surgery pembrolizumab OR Ipilimumab and Nivolumab + Core Biopsy/Cryoablation + Breast Surgery +Post Surgery Nivolumab

Drug: Pembrolizumab; Procedure: Core Biopsy/Cryoablation; Procedure: Breast Surgery; Drug: Ipilimumab; Drug: Nivolumab

Interventions

Pembrolizumab DRUG

Pembro will be administered 1-20 days before the cryoablation date per SOC and q3 weeks after surgery for 9 cycles per SOC.

Treatment Arm

Core Biopsy/Cryoablation PROCEDURE

US-guided core biopsy and cryoablation 7-10 days prior to surgery.

Treatment Arm

Breast Surgery PROCEDURE

Standard-of-care definitive surgery.

Treatment Arm

Ipilimumab DRUG

ipilimumab 1mg/Kg IV is administered 1-5 days prior to cryoablation.

Treatment Arm

Nivolumab DRUG

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.

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women age 18 years or older
• Confirmed histologic diagnosis of invasive carcinoma of the breast
• Pathology confirmation of invasive carcinoma (reported or requested and pending)
• ER, PR and HER2 negative on outside or Cedars Sinai biopsy report, where ER and PR negative are defined as staining present in ≤10% of invasive cancer cells by IHC, and HER2-negative is defined as IHC 0-1+ or FISH \<2.0. If ER, PR and HER2 status are not reported the results must be requested and pending.
• Operable tumor measuring ≥1.0 cm in maximal diameter
• Any nodal status allowed, including negative nodal status.
• Multifocal and multicentric disease is permitted if all foci have been biopsied and also meet the criteria for TNBC.
• Synchronous bilateral invasive breast cancer is permitted if all foci have been biopsied and also meet the criteria for TNBC.
• No indication of distant metastases
• Total mastectomy or lumpectomy planned
• Tumor amenable to cryoablation as determined by a study radiologist
• ECOG performance status score of 0 or 1.
• Screening laboratory values must meet the following criteria:
• White blood cells (WBCs) ≥ 2000/μL
• Absolute neutrophil count (ANC) ≥ 1500/μL

You may not qualify if:

• Medical history and concurrent diseases
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Note: Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
• Any underlying medical or psychiatric condition, which in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of AEs, such as a condition associated with frequent or poorly controlled diarrhea.
• A history of invasive malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer, or ovarian cancer.
• Has known active hepatitis B or hepatitis C.
• Prohibited Treatments and/or Therapies
• Chronic use of immunosuppressants and/or systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses). Brief periods of steroid use, for example for the management of chemotherapy-associated toxicities, are allowed. The use of corticosteroids on study is allowed for the treatment of immune related adverse events (irAEs) and other medical conditions including adrenal insufficiency.
• Any non-oncology live vaccine therapy used for prevention of infectious diseases within 3 weeks prior to first dose of ICI.
• Prior investigational agents within 3 weeks prior to ICI administration

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Susan G. Komen Breast Cancer Foundation: collaborator
• Bristol-Myers Squibb: collaborator
• Boston Scientific Corporation: collaborator
• American Society of Clinical Oncology: collaborator

Study Sites (4)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Providence Cancer Institute

Portland, Oregon, 97213, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pembrolizumab; Biopsy, Needle; Cryosurgery; Mastectomy, Segmental; Ipilimumab; Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Punctures; Investigative Techniques; Ablation Techniques; Mastectomy; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Heather McArthur, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: May 23, 2018
• First Posted: June 6, 2018
• Study Start: November 12, 2019
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2028
• Last Updated: March 27, 2026

Record last verified: 2026-03

Locations

US (4)