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

Early Phase 1

Withdrawn

• Conditions: Locally Advanced Breast Carcinoma; Metastatic Triple-Negative Breast Carcinoma; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8; Prognostic Stage IV Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8
• Interventions: Drug: Atezolizumab; Procedure: Cryosurgery; Drug: Nab-paclitaxel

• Registration Number: NCT04249167
• Lead Sponsor: Mayo Clinic

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 Timeline

• Study Start: 2020-01-23
• Study First Submitted: 2020-01-27
• Study First Submitted QC: 2020-01-29
• Study First Posted: 2020-01-30
• Primary Completion: 2021-11-17
• Study Completion: 2021-11-17
• Status Verified: 2021-12
• Last Update Submitted: 2023-01-05
• Last Update Posted: 2023-01-06

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Female
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (cryoablation, atezolizumab, nab-paclitaxel)	Cryosurgery	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.
Treatment (cryoablation, atezolizumab, nab-paclitaxel)	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.
Treatment (cryoablation, atezolizumab, nab-paclitaxel)	Atezolizumab	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.