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

NCT ID: NCT03546686

Last Updated: 2025-10-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-11-12

Study Completion Date

2028-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Breast Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment Arm

Pembrolizumab + Core Biopsy/Cryoablation + Breast Surgery +Post Surgery pembrolizumab

OR

Ipilimumab and Nivolumab + Core Biopsy/Cryoablation + Breast Surgery +Post Surgery Nivolumab

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type DRUG

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

Core Biopsy/Cryoablation

Intervention Type PROCEDURE

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

Breast Surgery

Intervention Type PROCEDURE

Standard-of-care definitive surgery.

Ipilimumab

Intervention Type DRUG

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

Nivolumab

Intervention Type 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.

Interventions

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Pembrolizumab

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

Intervention Type DRUG

Core Biopsy/Cryoablation

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

Intervention Type PROCEDURE

Breast Surgery

Standard-of-care definitive surgery.

Intervention Type PROCEDURE

Ipilimumab

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

Intervention Type DRUG

Nivolumab

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Women age 18 years or older
2. Confirmed histologic diagnosis of invasive carcinoma of the breast
3. Pathology confirmation of invasive carcinoma (reported or requested and pending)
4. 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.
5. Operable tumor measuring ≥1.0 cm in maximal diameter
6. Any nodal status allowed, including negative nodal status.
7. Multifocal and multicentric disease is permitted if all foci have been biopsied and also meet the criteria for TNBC.
8. Synchronous bilateral invasive breast cancer is permitted if all foci have been biopsied and also meet the criteria for TNBC.
9. No indication of distant metastases
10. Total mastectomy or lumpectomy planned
11. Tumor amenable to cryoablation as determined by a study radiologist
12. ECOG performance status score of 0 or 1.
13. Screening laboratory values must meet the following criteria:

* White blood cells (WBCs) ≥ 2000/μL
* Absolute neutrophil count (ANC) ≥ 1500/μL
* Platelets ≥ 100 x 103/μL ii. Hemoglobin ≥ 9.0 g/dL iii. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below): Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL
* AST/ALT ≤ 3 x upper limit of normal (ULN)
* Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert's syndrome, who must have total bilirubin \< 3.0 mg/dL)
14. Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab and, ipilimumab, and pembrolizumab to undergo five half-lives) after the last dose of investigational drug.
15. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG). Women must not be breastfeeding
16. Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.

Exclusion Criteria

* Medical history and concurrent diseases

1. 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.
2. 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.
3. 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.
4. Has known active hepatitis B or hepatitis C.
* Prohibited Treatments and/or Therapies

1. 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.
2. Any non-oncology live vaccine therapy used for prevention of infectious diseases within 3 weeks prior to first dose of ICI.
3. Prior investigational agents within 3 weeks prior to ICI administration
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Susan G. Komen Breast Cancer Foundation

OTHER

Sponsor Role collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

Boston Scientific Corporation

INDUSTRY

Sponsor Role collaborator

American Society of Clinical Oncology

OTHER

Sponsor Role collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Heather McArthur

Associate Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Heather McArthur, MD

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Locations

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Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status ACTIVE_NOT_RECRUITING

Ohio State University Medical Center

Columbus, Ohio, United States

Site Status COMPLETED

Providence Cancer Institute

Portland, Oregon, United States

Site Status ACTIVE_NOT_RECRUITING

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Meredith Carter, MS

Role: CONTACT

214-648-7097

Facility Contacts

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Meredith Carter, MS

Role: primary

214-648-7097

Other Identifiers

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STU-2021-1043

Identifier Type: -

Identifier Source: org_study_id

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