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Cryoablation, Atezolizumab/Nab-paclitaxel for Locally Advanced or Metastatic Triple Negative Breast Cancer

Primary Purpose

Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8

Status
Withdrawn
Phase
Early Phase 1
Locations
Study Type
Interventional
Intervention
Atezolizumab
Cryosurgery
Nab-paclitaxel
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anatomic Stage III Breast Cancer AJCC v8

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Locally advanced or metastatic PD-L1 positive TNBC (TNBC is defined as estrogen receptor [ER] < 10%, progesterone receptor [PR] < 10%, and HER2 non-amplified; and PD-L1 positive is defined as >= 1%.)
  • Presents with primary breast tumor lesion amenable to cryoablation
  • Have at least one additional distant lesion feasible for biopsies
  • Agreeable to start on atezolizumab and nab-paclitaxel as per standard of care
  • Patients with locally advanced disease must be ineligible for curative surgery for any reason, including but not limited to comorbid status precluding surgery due to safety, unresectability, or patient refusal
  • Patient may have received prior systemic chemotherapy regimens

Exclusion Criteria:

  • History of autoimmune disease
  • History of human immunodeficiency virus (HIV)
  • Previous immune checkpoint targeting therapies
  • No primary breast lesion amenable for cryoablation due to size (greater than 5 cm) or location (proximity of < 0.5 cm to the skin or nipple-areola complex)
  • Pregnancy

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Treatment (cryoablation, atezolizumab, nab-paclitaxel)

    Arm Description

    Patients undergo cryoablation of the primary tumor over about 1 hour. After 2-3 weeks, patients receive atezolizumab IV on days 1 and 15 and nab-paclitaxel IV on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Outcomes

    Primary Outcome Measures

    Safety and Feasibility of cryoablation with systemic atezolizumab/nab-paclitaxel
    All adverse events will be reported by grade using frequencies and relative frequencies, and rates will be estimated using a 90% confidence interval obtained using Jeffrey's prior method.

    Secondary Outcome Measures

    Abscopal response in the distant non-cryoablated site(s)
    Will be assessed by using digital spatial profiling. Each immune response will be treated as a continuous variable, and will be summarized using frequencies and relative frequencies. The overall immune response rate will be estimated using a 90% confidence interval obtained using Jeffrey's prior method.
    Systemic effector cell and cytokine responses
    Each immune response will be treated as a continuous variable, and will be summarized using frequencies and relative frequencies. The overall immune response rate will be estimated using a 90% confidence interval obtained using Jeffrey's prior method.
    Overall survival
    Will be summarized using standard Kaplan-Meier methods. OS defined as Time from cryoablation until death due to any cause or last follow-up
    Disease-specific survival
    Will be summarized using standard Kaplan-Meier methods. OS defined as Time from cryoablation until death due to breast cancer
    Progression-free survival
    Will be summarized using standard Kaplan-Meier methods.

    Full Information

    First Posted
    January 27, 2020
    Last Updated
    January 5, 2023
    Sponsor
    Mayo Clinic
    Collaborators
    National Cancer Institute (NCI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04249167
    Brief Title
    Cryoablation, Atezolizumab/Nab-paclitaxel for Locally Advanced or Metastatic Triple Negative Breast Cancer
    Official Title
    Cryoablation and Anti-PD-L1 Immunotherapy for Triple Negative Breast Cancer (TNBC)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    December 2021
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    study was dropped
    Study Start Date
    January 23, 2020 (Actual)
    Primary Completion Date
    November 17, 2021 (Actual)
    Study Completion Date
    November 17, 2021 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Mayo Clinic
    Collaborators
    National Cancer Institute (NCI)

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This early phase I trial studies the side effects and feasibility of cryoablation, atezolizumab, and nab-paclitaxel in treating patients with triple negative breast cancer that has spread to nearby tissue or lymph nodes (locally advanced) or has spread to other places in the body (metastatic). Cryosurgery, also known as cryoablation or cryotherapy, kills tumor cells by freezing them. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving cryoablation, atezolizumab and nab-paclitaxel may improve response to the disease.
    Detailed Description
    PRIMARY OBJECTIVE: I. To determine the safety and feasibility of cryoablation of a primary breast tumor followed by PD-L1 blockade in patients with locally advanced or metastatic triple negative breast cancer (TNBC). SCONDARY OBJECTIVE: I. To evaluate the systemic immune response to cryoablation of a primary breast tumor and PD-L1 blockade. OUTLINE: Patients undergo cryoablation of the primary tumor over about 1 hour. After 2-3 weeks, patients receive atezolizumab intravenously (IV) on days 1 and 15 and nab-paclitaxel IV on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 2-3 weeks post surgery and then periodically thereafter.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8, Anatomic Stage IIIC Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Locally Advanced Breast Carcinoma, Metastatic Triple-Negative Breast Carcinoma, Prognostic Stage III Breast Cancer AJCC v8, Prognostic Stage IIIA Breast Cancer AJCC v8, Prognostic Stage IIIB Breast Cancer AJCC v8, Prognostic Stage IIIC Breast Cancer AJCC v8, Prognostic Stage IV Breast Cancer AJCC v8

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Early Phase 1
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Treatment (cryoablation, atezolizumab, nab-paclitaxel)
    Arm Type
    Experimental
    Arm Description
    Patients undergo cryoablation of the primary tumor over about 1 hour. After 2-3 weeks, patients receive atezolizumab IV on days 1 and 15 and nab-paclitaxel IV on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Intervention Type
    Drug
    Intervention Name(s)
    Atezolizumab
    Other Intervention Name(s)
    MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq
    Intervention Description
    Given IV
    Intervention Type
    Procedure
    Intervention Name(s)
    Cryosurgery
    Other Intervention Name(s)
    Ablation, Cryo, Cryoablation, cryosurgical ablation
    Intervention Description
    Undergo cryoablation of the primary tumor
    Intervention Type
    Drug
    Intervention Name(s)
    Nab-paclitaxel
    Other Intervention Name(s)
    ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel, Albumin-Stabilized Nanoparticle Paclitaxel, Nanoparticle Albumin-bound Paclitaxel, Nanoparticle Paclitaxel, Paclitaxel Albumin, paclitaxel albumin-stabilized nanoparticle formulation, Protein-bound Paclitaxel
    Intervention Description
    Given IV
    Primary Outcome Measure Information:
    Title
    Safety and Feasibility of cryoablation with systemic atezolizumab/nab-paclitaxel
    Description
    All adverse events will be reported by grade using frequencies and relative frequencies, and rates will be estimated using a 90% confidence interval obtained using Jeffrey's prior method.
    Time Frame
    5 years
    Secondary Outcome Measure Information:
    Title
    Abscopal response in the distant non-cryoablated site(s)
    Description
    Will be assessed by using digital spatial profiling. Each immune response will be treated as a continuous variable, and will be summarized using frequencies and relative frequencies. The overall immune response rate will be estimated using a 90% confidence interval obtained using Jeffrey's prior method.
    Time Frame
    5 years
    Title
    Systemic effector cell and cytokine responses
    Description
    Each immune response will be treated as a continuous variable, and will be summarized using frequencies and relative frequencies. The overall immune response rate will be estimated using a 90% confidence interval obtained using Jeffrey's prior method.
    Time Frame
    At baseline, after cryoablation, and after atezolizumab and nab-paclitaxel
    Title
    Overall survival
    Description
    Will be summarized using standard Kaplan-Meier methods. OS defined as Time from cryoablation until death due to any cause or last follow-up
    Time Frame
    Assessed up to 5 years
    Title
    Disease-specific survival
    Description
    Will be summarized using standard Kaplan-Meier methods. OS defined as Time from cryoablation until death due to breast cancer
    Time Frame
    Time from cryoablation until death due to breast cancer or last follow-up, assessed up to 5 years
    Title
    Progression-free survival
    Description
    Will be summarized using standard Kaplan-Meier methods.
    Time Frame
    Time from cryoablation to tumor growth as defined by modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria, assessed up to 5 years

    10. Eligibility

    Sex
    Female
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Locally advanced or metastatic PD-L1 positive TNBC (TNBC is defined as estrogen receptor [ER] < 10%, progesterone receptor [PR] < 10%, and HER2 non-amplified; and PD-L1 positive is defined as >= 1%.) Presents with primary breast tumor lesion amenable to cryoablation Have at least one additional distant lesion feasible for biopsies Agreeable to start on atezolizumab and nab-paclitaxel as per standard of care Patients with locally advanced disease must be ineligible for curative surgery for any reason, including but not limited to comorbid status precluding surgery due to safety, unresectability, or patient refusal Patient may have received prior systemic chemotherapy regimens Exclusion Criteria: History of autoimmune disease History of human immunodeficiency virus (HIV) Previous immune checkpoint targeting therapies No primary breast lesion amenable for cryoablation due to size (greater than 5 cm) or location (proximity of < 0.5 cm to the skin or nipple-areola complex) Pregnancy
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Emmanuel M Gabriel
    Organizational Affiliation
    Mayo Clinic
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Links:
    URL
    https://www.mayo.edu/research/clinical-trials
    Description
    Mayo Clinic Clinical Trials

    Learn more about this trial

    Cryoablation, Atezolizumab/Nab-paclitaxel for Locally Advanced or Metastatic Triple Negative Breast Cancer

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