Clinical trial NCT04249167: Cryoablation, Atezolizumab/Nab-paclitaxel for Locally Advanced or Metastatic Triple Negative Breast Cancer
Official title: Cryoablation and Anti-PD-L1 Immunotherapy for Triple Negative Breast Cancer (TNBC)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
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
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
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2020-01-30
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety and Feasibility of cryoablation with systemic atezolizumab/nab-paclitaxel
timeFrame: 5 years
Secondary outcomes:
measure: Abscopal response in the distant non-cryoablated site(s)
timeFrame: 5 years
measure: Systemic effector cell and cytokine responses
timeFrame: At baseline, after cryoablation, and after atezolizumab and nab-paclitaxel
measure: Overall survival
timeFrame: Assessed up to 5 years
measure: Disease-specific survival
timeFrame: Time from cryoablation until death due to breast cancer or last follow-up, assessed up to 5 years
measure: Progression-free survival
timeFrame: Time from cryoablation to tumor growth as defined by modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria, assessed up to 5 years
Other outcomes:
Locations:
Study officials:
affiliation: Mayo Clinic
name: Emmanuel M Gabriel
role: PRINCIPAL_INVESTIGATOR
References: