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

Anatomic Stage III Breast Cancer AJCC v8 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04249167
• Other study ID #: MC2031
• Secondary ID: NCI-2020-0033319
• Status: Withdrawn
• Phase: Early Phase 1
• Start date: January 23, 2020
• Est. completion date: November 17, 2021

Study information

• Verified date: December 2021
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 17, 2021
• Est. primary completion date: November 17, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• 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
• Breast Neoplasms
• Carcinoma
• 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
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Atezolizumab
Given IV

Procedure:
• Cryosurgery
Undergo cryoablation of the primary tumor

Drug:
• Nab-paclitaxel
Given IV

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Mayo Clinic Clinical Trials