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

Sponsor

Mayo Clinic (Other)

Overall Status

Withdrawn

CT.gov ID

NCT04249167

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Arm

21.8

Actual Duration (Months)

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Atezolizumab Procedure: Cryosurgery Drug: Nab-paclitaxel	Early Phase 1

Detailed Description

PRIMARY OBJECTIVE:

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:

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Cryoablation and Anti-PD-L1 Immunotherapy for Triple Negative Breast Cancer (TNBC)

Actual Study Start Date :

Jan 23, 2020

Actual Primary Completion Date :

Nov 17, 2021

Actual Study Completion Date :

Nov 17, 2021

Arms and Interventions

Arm	Intervention/Treatment
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.	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

Arm

Intervention/Treatment

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.

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

Outcome Measures

Primary Outcome Measures

Safety and Feasibility of cryoablation with systemic atezolizumab/nab-paclitaxel [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.

Secondary Outcome Measures

Abscopal response in the distant non-cryoablated site(s) [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 [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 [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 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 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts 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