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Pembrolizumab and Cryoablation for the Treatment of Metastatic or Locally Advanced Triple Negative Breast Cancer
Trial Status: active
This phase I trial compares the safety and effectiveness of pembrolizumab plus cryoablation to pembrolizumab alone in treating patients with triple negative breast cancer (TNBC) that has spread from where it first started (primary site) to other places in the body (metastatic) or has spread to nearby tissue or lymph nodes (locally advanced). Pembrolizumab is an immunotherapy drug called a monoclonal antibody. It works by blocking a protein, PD-1 (programmed cell death receptor 1), that usually acts as a “brake” on the immune system. Blocking this protein is like releasing the brakes, so that the immune system can target and kill tumor cells. Cryoablation uses extreme cold to kill tumor cells in a specific area of the body. The radiologist uses imaging (for example, with ultrasound) to insert a needle directly into a cancerous tumor. Very cold temperatures are then applied through the needle into the tumor to kill the tumor cells. Some of the killed tumor cells will be broken into pieces that can be recognized and targeted by a patient’s immune system. Cryoablation may be particularly useful in combination with drugs that help boost the immune system (immunotherapies like pembrolizumab). Giving pembrolizumab and cryoablation may be safe and effective in treating patients with metastatic or locally advanced TNBC.
Inclusion Criteria
Patients ≥ 18 years of age
Confirmed histologic diagnosis of metastatic TNBC
1 site amenable cryoablation of at least 1.5 cm in size as determined by an interventional radiologist. Eligible cryoablation sites include (but not limited to) soft tissue, liver, lung, and bone as determined by an interventional radiologist to be safest and most feasible.
Physically fit (clinically eligible) to undergo cryoablation as per usual clinical practice
Per clinical guidelines, women of childbearing age should use effective contraception during treatment with pembrolizumab and for at least 4 months after the last dose of the drug, which will be assessed and monitored by, and the responsibility of, the patient's medical oncologist (not study investigators or research team) as pembrolizumab is standard of care. Memorial Sloan Kettering Cancer Center Pregnancy Standards will be followed prior to cryoablation. That is, female patients that are 11-50 years of age and of childbearing potential will undergo a pregnancy test within 2 weeks (15 days) before cryoablation. Pregnancy test will not be required in patients with bilateral oophorectomy, bilateral salpingectomy, bilateral salpingectomy-oophorectomy, hysterectomy, menopause (no menses ≥ 1 year prior to treatment or after completion of all treatment), or surgical sterilization (i.e. tubal ligation or blockage), with documentation of permanent exemptions in CIS ("Pregnancy Testing Exemption").
Pembrolizumab therapy (200 mg every 3 weeks) planned as part of standard of care as first, second, or third line of therapy
* Eligible for PD-1 inhibitor per the patient's medical oncologist, with planned treatment with PD-1 inhibitor per the patient's medical oncologist. Additional systemic therapy is per the patient's medical oncologist. The following systemic therapy will be accepted (the timing of the systemic therapy relative to pembrolizumab and cryoablation is not restricted):
** Capecitabine (Xeloda, available as a generic drug)
** Carboplatin (Paraplatin, available as a generic drug)
** Cisplatin (Platinol, available as a generic drug)
** Cyclophosphamide (Cytoxan, available as a generic drug)
** Docetaxel (Taxotere)
** Doxorubicin (Adriamycin, available as a generic drug)
** Pegylated liposomal doxorubicin (Doxil)
** Epirubicin (Ellence, available as a generic drug)
** Eribulin (Halaven)
** Fluorouracil (5-FU, Adrucil, available as a generic drug)
** Gemcitabine (Gemzar, available as a generic drug)
** Ixabepilone (Ixempra)
** Methotrexate (available as a general drug)
** Nab-paclitaxel (Abraxane)
** Paclitaxel (Taxol, available as a generic drug)
** Vinorelbine (Navelbine, available as a generic drug)
Exclusion Criteria
Patient not eligible for PD-1 inhibitor per the patient’s medical oncologist
No disease amenable for cryoablation
Pembrolizumab therapy not planned as part of standard of care
Additional locations may be listed on ClinicalTrials.gov for NCT06246968.
I. Assess changes in CD4-PD1 in the blood after cryoablation in patients with metastatic or locally advanced triple negative breast cancer (TNBC).
SECONDARY OBJECTIVES:
I. Describe and estimate differences in changes in immune markers separately in the blood and in tumor after cryoablation in patients who respond versus those who do not respond based on clinical imaging obtained 3 months after initiation of pembrolizumab.
II. Describe changes in immune markers in the blood in patients with cryoablation relative to those without cryoablation.
III. Describe imaging response at 3 months after initiation of pembrolizumab in patients with cryoablation relative to those without cryoablation.
IV. Describe progression-free survival and overall survival in patients with cryoablation relative to those without cryoablation.
OUTLINE: Participants are randomized to 1 of 2 arms.
ARM I: Patients receive standard of care (SOC) pembrolizumab intravenously (IV) beginning on day 1 every 3 weeks (Q3W) in the absence of disease progression or unacceptable toxicity. Patients also undergo cryoablation on day 7. Patients undergo positron emission tomography (PET)/computed tomography (CT), CT, or magnetic resonance imaging (MRI) during screening and follow-up and blood sample collection throughout the study.
ARM II: Patients receive SOC pembrolizumab IV on day 1 and every 3 weeks (Q3W) in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT, CT, or MRI during screening and follow-up and blood sample collection throughout the study. Patients who cancer does not respond to the standard treatment approach (pembrolizumab alone) or cancer gets worse, may receive the combination of pembrolizumab and cryoablation.
After completion of study treatment, patients are followed for up to 2 years.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
