Clinical Trials /

Focused Ultrasound and Pembrolizumab in Metastatic Breast Cancer

NCT03237572

Description:

This pilot study evaluates the use of high-intensity focused ultrasound (HIFU) combined with pembrolizumab in patients with metastatic breast cancer. One-half of participants will be randomized to receive the first dose of pembrolizumab after HIFU and one-half of participants will be randomized to receive their first dose of pembrolizumab before HIFU.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Focused Ultrasound and Pembrolizumab in Metastatic Breast Cancer
  • Official Title: Focused Ultrasound Therapy to Augment Antigen Presentation and Immune-Specificity of Checkpoint Inhibitor Therapy With Pembrolizumab in Metastatic Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 19900
  • NCT ID: NCT03237572

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
PembrolizumabKeytrudaArm A: 1st dose of pembrolizumab after HIFU

Purpose

This pilot study evaluates the use of high-intensity focused ultrasound (HIFU) combined with pembrolizumab in patients with metastatic breast cancer. One-half of participants will be randomized to receive the first dose of pembrolizumab after HIFU and one-half of participants will be randomized to receive their first dose of pembrolizumab before HIFU.

Trial Arms

NameTypeDescriptionInterventions
Arm A: 1st dose of pembrolizumab after HIFUExperimentalPembrolizumab (200 mg) administered intravenously, days 22, 43, 64, followed by day 1 of each ensuing 3 -week cycle. Focused ultrasound tumor ablation day 15. High-intensity focused ultrasound ablation will target 50% of the tumor, up to 3 cubic centimeters.
  • Pembrolizumab
Arm B: 1st dose of pembrolizumab before HIFUExperimentalPembrolizumab (200 mg) intravenously, days 1, 22, 43, 64, followed by day 1 of each ensuing 3 -week cycle. Focused ultrasound tumor ablation day 15. High-intensity focused ultrasound ablation will target 50% of the tumor, up to 3 cubic centimeters.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria (summary):

          -  Histologically confirmed metastatic or unresectable breast cancer

          -  Any receptor status (estrogen receptor, progesterone receptor, HER2 receptor).
             Patients who are HR+ should also no longer be candidates for hormonal-based therapy.
             Patients who are HER2+ should have progressed on or no longer be candidates for
             available HER2 directed therapy. Hormonal therapy must be stopped prior to day 1 of
             treatment.

          -  Patients must have had at least one prior line of therapy for breast cancer in the
             metastatic setting.

          -  Patients must have an accessible lesion in the breast/chest wall/axilla which has not
             been previously thermally ablated. Prior breast irradiation is acceptable if the
             lesion has recurred or grown following radiation.

          -  Patients must agree to use an adequate method of contraception for the course of the
             study through 120 days after the last dose of study medication.

          -  Patients must have at least one target lesion in breast/chest wall/axilla which is
             amenable to application of high intensity focused ultrasound:

          -  Patients must be willing to provide tissue from a newly obtained core or excisional
             biopsy of a tumor lesion.

          -  Performance status of 0 or 1 on the ECOG Performance Scale.

          -  Adequate organ function

        Exclusion Criteria (summary):

          -  Patients currently participating and receiving study therapy or patients who have
             participated in a study of an investigational agent and received study therapy or used
             an investigational device within 4 weeks of the first dose of treatment.

          -  Patients with a diagnosis of immunodeficiency, patients receiving systemic steroid
             therapy or, patients who have received any other form of immunosuppressive therapy
             within 7 days prior to the first dose of trial treatment.

          -  Patients with a known history of active Tuberculosis

          -  Hypersensitivity to pembrolizumab or any of its excipients

          -  Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1.
             Patients who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events
             due to agents administered more than 4 weeks earlier are excluded.

          -  Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2
             weeks prior to study Day 1. Patients who has not recovered (i.e., ≤ Grade 1 or at
             baseline) from adverse events due to a previously administered agent.

          -  Known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer.

          -  Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

          -  Active autoimmune disease that has required systemic treatment in the past 2 years.

          -  History of (non-infectious) pneumonitis that required steroids or current pneumonitis.

          -  Active infection requiring systemic therapy.

          -  Pregnancy

          -  Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent within the prior 24
             weeks.

          -  Known history of Human Immunodeficiency Virus (HIV)

          -  Receipt of a live vaccine within 30 days of planned start of study therapy.

          -  Breast implant on the side of the body that will receive HIFU application
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in tumor infiltrating lymphocytes
Time Frame:baseline and week 4
Safety Issue:
Description:Change in proportion of CD8+ tumor infiltrating lymphocytes (ration CD8+/CD4+) in the primary ablation zone

Secondary Outcome Measures

Measure:Adverse event profile of pembrolizumab and HIFU
Time Frame:From date of randomization through 30 days following cessation of treatment
Safety Issue:
Description:Toxicities from the combination of pembrolizumab and HIFU

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Patrick Dillon, MD

Trial Keywords

  • breast cancer
  • pembrolizumab
  • focused ultrasound
  • immunotherapy

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