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Breast CancerPhase 2NCT03546686

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

A Phase 2 study testing Pembrolizumab, Core Biopsy/Cryoablation and Breast Surgery in people with Breast Cancer, run by University of Texas Southwestern Medical Center at 4 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Pembrolizumab, Core Biopsy/Cryoablation and Breast Surgery
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
4 sitesUnited States
Study dates
12 Nov 2019to Jun 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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
  • 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)
  • 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.
  • 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
  • Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.

Who cannot join

  • 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
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  • 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

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

  • Providence Cancer Institute

    Portland, Oregon, 97213

Other trials in United States

About this study

Official title: A Single Arm Phase 2 Study of Peri-Operative Immune Checkpoint Inhibition and Cryoablation in Women With Hormone Receptor-Negative, HER2-Negative Early Stage/Resectable Breast Cancer.

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.

Read the detailed description

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
Breast Cancer
Being tested
Pembrolizumab, Core Biopsy/Cryoablation, Breast Surgery, Ipilimumab, Nivolumab
Keywords
Hormone Receptor Negative, Her2- Negative, Resectable Breast Cancer, breast cancer, immunotherapy, Ipilimumab, Nivolumab, Cryoablation
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    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/CryoablationProcedure or surgery

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

  • Breast SurgeryProcedure or surgery

    Standard-of-care definitive surgery.

  • IpilimumabDrug

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

  • NivolumabDrug

    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.

Study groups in NCT03546686
Study groupRoleWhat they receive
Treatment ArmExperimentalPembrolizumab + Core Biopsy/Cryoablation + Breast Surgery +Post Surgery pembrolizumab OR Ipilimumab and Nivolumab + Core Biopsy/Cryoablation + Breast Surgery +Post Surgery Nivolumab
Receives: Drug: Pembrolizumab; Procedure: Core Biopsy/Cryoablation; Procedure: Breast Surgery; Drug: Ipilimumab; Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 36 Months

Secondary outcomes (4)

  1. 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

    Measured: 36 Months

  2. 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)

    Measured: 36 Months

  3. 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.

    Measured: 36 Months

  4. Overall Safety

    Number of related adverse events based on CTCAE v.5.0

    Measured: 36 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jun 2018
  2. Study start12 Nov 2019
  3. Primary completionJun 2027 (estimated)
  4. Study completionJun 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03546686
Sponsor's protocol ID
STU-2021-1043
Status last verified
Jul 2026
First submitted
23 May 2018
Last updated
22 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab, Core Biopsy/Cryoablation and Breast Surgery in people with Breast Cancer, run by University of Texas Southwestern Medical Center at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 22 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-Free Survival (time frame: 36 Months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03546686.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2026.

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