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

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ClinicalTrials.gov Identifier: NCT04249167
Recruitment Status : Recruiting
First Posted : January 30, 2020
Last Update Posted : February 5, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Tracking Information
First Submitted Date  ICMJE January 27, 2020
First Posted Date  ICMJE January 30, 2020
Last Update Posted Date February 5, 2020
Actual Study Start Date  ICMJE January 23, 2020
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 29, 2020)
Safety and Feasibility of cryoablation with systemic atezolizumab/nab-paclitaxel [ Time Frame: 5 years ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 31, 2020)
  • Abscopal response in the distant non-cryoablated site(s) [ Time Frame: 5 years ]
    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 [ Time Frame: At baseline, after cryoablation, and after atezolizumab and nab-paclitaxel ]
    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 [ Time Frame: Assessed up to 5 years ]
    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 [ Time Frame: Time from cryoablation until death due to breast cancer or last follow-up, assessed up to 5 years ]
    Will be summarized using standard Kaplan-Meier methods. OS defined as Time from cryoablation until death due to breast cancer
  • 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 ]
    Will be summarized using standard Kaplan-Meier methods.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 29, 2020)
  • Abscopal response in the distant non-cryoablated site(s) [ Time Frame: 5 years ]
    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 [ Time Frame: At baseline, after cryoablation, and after atezolizumab and nab-paclitaxel ]
    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 [ Time Frame: Assessed up to 5 years ]
    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 [ Time Frame: Time from cryoablation until death due to breast cancer or last follow-up, assessed up to 5 years ]
  • 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 ]
    Will be summarized using standard Kaplan-Meier methods.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cryoablation, Atezolizumab/Nab-paclitaxel for Locally Advanced or Metastatic Triple Negative Breast Cancer
Official Title  ICMJE Cryoablation and Anti-PD-L1 Immunotherapy for Triple Negative Breast Cancer (TNBC)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: Atezolizumab
    Given IV
    Other Names:
    • MPDL 3280A
    • MPDL 328OA
    • MPDL-3280A
    • MPDL3280A
    • MPDL328OA
    • RG7446
    • RO5541267
    • Tecentriq
  • Procedure: Cryosurgery
    Undergo cryoablation of the primary tumor
    Other Names:
    • Ablation, Cryo
    • Cryoablation
    • cryosurgical ablation
  • Drug: Nab-paclitaxel
    Given IV
    Other Names:
    • 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
Study Arms  ICMJE Experimental: Treatment (cryoablation, atezolizumab, nab-paclitaxel)
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.
Interventions:
  • Drug: Atezolizumab
  • Procedure: Cryosurgery
  • Drug: Nab-paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 29, 2020)
5
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2020
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04249167
Other Study ID Numbers  ICMJE MC2031
NCI-2020-00333 ( Other Grant/Funding Number: CTRP (Clinical Trial Reporting Program) )
19-008704 ( Other Identifier: Mayo Clinic in Florida )
P30CA015083 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Emmanuel M Gabriel Mayo Clinic
PRS Account Mayo Clinic
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP