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

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

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.

Study Overview

• Status: Withdrawn
• 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; 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; Anatomic Stage IV Breast Cancer AJCC v8; Prognostic Stage IV Breast Cancer AJCC v8; Metastatic Triple-Negative Breast Carcinoma; Locally Advanced Breast Carcinoma
• Intervention / Treatment: Drug: Nab-paclitaxel; Drug: Atezolizumab; Procedure: Cryosurgery

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: Interventional
• Phase: Early Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: Nab-paclitaxel; Given IV; Other Names: ABI-007; Abraxane; Albumin-bound Paclitaxel; ABI 007; Albumin-Stabilized Nanoparticle Paclitaxel; Nanoparticle Albumin-bound Paclitaxel; Nanoparticle Paclitaxel; Paclitaxel Albumin; paclitaxel albumin-stabilized nanoparticle formulation; Protein-bound Paclitaxel; Drug: Atezolizumab; Given IV; Other Names: Tecentriq; MPDL3280A; RO5541267; RG7446; MPDL 3280A; MPDL 328OA; MPDL-3280A; MPDL328OA; Procedure: Cryosurgery; Undergo cryoablation of the primary tumor; Other Names: Cryoablation; cryosurgical ablation; Ablation, Cryo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	5 years
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.	At baseline, after cryoablation, and after atezolizumab and nab-paclitaxel
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	Assessed up to 5 years
Disease-specific survival	Will be summarized using standard Kaplan-Meier methods. OS defined as Time from cryoablation until death due to breast cancer	Time from cryoablation until death due to breast cancer or last follow-up, assessed up to 5 years
Progression-free survival	Will be summarized using standard Kaplan-Meier methods.	Time from cryoablation to tumor growth as defined by modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria, assessed up to 5 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Emmanuel M Gabriel, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2020
• Primary Completion (Actual): November 17, 2021
• Study Completion (Actual): November 17, 2021

Study Registration Dates

• First Submitted: January 27, 2020
• First Submitted That Met QC Criteria: January 29, 2020
• First Posted (Actual): January 30, 2020

Study Record Updates

• Last Update Posted (Estimate): January 6, 2023
• Last Update Submitted That Met QC Criteria: January 5, 2023
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Breast Diseases; Breast Neoplasms; Carcinoma; Triple Negative Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Albumin-Bound Paclitaxel; Antibodies, Monoclonal; Atezolizumab
• Other Study ID Numbers: MC2031; NCI-2020-00333 (Other Grant/Funding Number: CTRP (Clinical Trial Reporting Program)); 19-008704 (Other Identifier: Mayo Clinic in Florida)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No