Clinical Trials /

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

NCT04249167

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • 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)

Clinical Trial IDs

  • ORG STUDY ID: MC2031
  • SECONDARY ID: NCI-2020-00333
  • SECONDARY ID: 19-008704
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT04249167

Conditions

  • 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

Interventions

DrugSynonymsArms
AtezolizumabMPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, TecentriqTreatment (cryoablation, atezolizumab, nab-paclitaxel)
Nab-paclitaxelABI 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 PaclitaxelTreatment (cryoablation, atezolizumab, nab-paclitaxel)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (cryoablation, atezolizumab, nab-paclitaxel)ExperimentalPatients 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.
  • Atezolizumab
  • Nab-paclitaxel

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and Feasibility of cryoablation with systemic atezolizumab/nab-paclitaxel
Time Frame:5 years
Safety Issue:
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.

Secondary Outcome Measures

Measure:Abscopal response in the distant non-cryoablated site(s)
Time Frame:5 years
Safety Issue:
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.
Measure:Systemic effector cell and cytokine responses
Time Frame:At baseline, after cryoablation, and after atezolizumab and nab-paclitaxel
Safety Issue:
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.
Measure:Overall survival
Time Frame:Assessed up to 5 years
Safety Issue:
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
Measure:Disease-specific survival
Time Frame:Time from cryoablation until death due to breast cancer or last follow-up, assessed up to 5 years
Safety Issue:
Description:Will be summarized using standard Kaplan-Meier methods. OS defined as Time from cryoablation until death due to breast cancer
Measure:Progression-free survival
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
Safety Issue:
Description:Will be summarized using standard Kaplan-Meier methods.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mayo Clinic

Last Updated

February 5, 2020