Microwave Ablation Combined With Camrelizumab in the Treatment of Early Breast Cancer

A Pilot Study of Single-Dose Camrelizumab and/or Microwave Ablation in Women With Early-Stage Breast Cancer

Ablative therapy, as a local treatment modality for tumors, has an immune activating effect. To explore the synergistic effect of microwave ablation combined with PD-1 inhibitors, this prospective, open-label, multi-cohort, single-center clinical study was conducted. To compare the feasibility and safety of preoperative microwave ablation alone, with or without camrelizumab in patients with early newly diagnosed breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Procedure: Microwave Ablation; Procedure: Breast Surgery; Drug: Camrelizumab

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • The First Affiliated Hospital of Nanjing medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Female.
2. Age 20-65 years.
3. Invasive carcinoma confirmed by core biopsy.
4. Newly diagnosed breast cancer patients, without adjuvant therapy.
5. Imaging findings showed a single breast tumor with a maximum diameter of 3 cm, no distant metastasis, and no invasion of the skin and chest wall.
6. Systematic ultrasound is able to visualize lesions.
7. Surgical treatment was planned.

8. The functional level of major organs must meet the following requirements:

   1. blood routine: neutrophil (ANC) ≥ 1.5 × 109/L; platelet count (PLT) ≥ 90 × 109/L; hemoglobin (Hb) ≥ 90 g/L;
   2. blood biochemistry: total bilirubin (TBIL) ≤ upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × ULN; alkaline phosphatase ≤ 2.5 × ULN; blood urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 × ULN;
   3. coagulation: international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN; activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
   4. Heart: left ventricular ejection fraction (LVEF) ≥ 50% as assessed by echocardiography (ECHO) or multigated acquisition (MUGA).
   5. Thyroid function: thyroid stimulating hormone (TSH) ≤ ULN; if abnormal, T3 and T4 levels should be investigated, and normal T3 and T4 levels can be included.
   6. Urinalysis: urine protein < 2 +, if urine protein ≥ 2 +, 24-hour urine protein quantification must show protein ≤ 1 g.
9. Voluntarily participate in this study, sign informed consent, have good compliance and are willing to cooperate with follow-up.

Exclusion Criteria:

1. Tumor involving skin, ulceration, inflammatory breast cancer patients
2. Fatty breast cancer.
3. Tumors on the deep surface of areolar region
4. KPS score < 70, or ECOG score > 2
5. Patients with a history of concomitant collagen connective tissue disease, or any active autoimmune disease or autoimmune disease.
6. Prior radiotherapy or prior use of investigational drugs or other immunosuppressive agents
7. Heart, brain, lung, kidney and other vital organ failure, liver and kidney dysfunction;
8. Uncorrectable severe coagulopathy
9. Patient is pregnant or lactating
10. Poor glycemic control in diabetes
11. Patients with foreign body implantation around the tumor
12. Patients with severe scars on the skin of the treatment area (protruding from the skin surface, width ≥ 1 cm)
13. History of chronic immunosuppression, prior immunotherapy, recent vaccination (< 4 weeks)
14. Human immunodeficiency virus (HIV) infection, active hepatitis B (hepatitis B indicates antigen positive and HBV DNA ≥ 500 IU/ml), hepatitis C (hepatitis C antibody positive and HCV-RNA above the lower limit of detection of the analytical method).
15. Concurrent medical conditions that, in the judgment of the investigator, would jeopardize the subject's safety, could confound the study results, or affect the subject's completion of this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Microwave Ablation alone; Microwave Ablation+ Breast Surgery	Procedure: Microwave Ablation; Image-guided microwave ablation 7-10 days prior to surgery; Procedure: Breast Surgery; Standard of care breast conserving surgery or radical mastectmoy
Experimental: Camrelizumab alone; Camrelizumab+ Breast Surgery	Procedure: Breast Surgery; Standard of care breast conserving surgery or radical mastectmoy; Drug: Camrelizumab; Camrelizumab 200 mg was given a few days after microwave ablation; Other Names: SHR-1210
Experimental: Microwave Ablation & Camrelizumab; Microwave Ablation + Camrelizumab + Breast Surgery	Procedure: Microwave Ablation; Image-guided microwave ablation 7-10 days prior to surgery; Procedure: Breast Surgery; Standard of care breast conserving surgery or radical mastectmoy; Drug: Camrelizumab; Camrelizumab 200 mg was given a few days after microwave ablation; Other Names: SHR-1210

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Microwave Ablation Combined With Camrelizumab	Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 5.0	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete ablation rate	The proportion of patients with complete ablation was calculated for all patients. Complete ablation was defined as: tissue section at the ablation margin that was negative by histochemical staining.	1 day
Negative predictive value of ultrasound	Preoperative ultrasonography was performed. The negative predictive value of ultrasound was calculated by comparing the pathology report. Negative predictive value = number of patients with negative pathology and negative ultrasound/number of patients with negative ultrasound	1 day
Assessment of Immunogenicity	Proportion of subjects with immune response to synergistic therapy detected by biomarkers in peripheral blood samples	3 months
Breast self evaluation	Breast self evaluation for patients will be assessed by Functional Assessment of Cancer Therapy - Breast (FACT-B) scale scores.The FACT-B consists of 44 self-report items and assesses the specific breast cancer-related quality of life on 4 general and 1 breast-cancer specific subscale. A higher score indicates a higher cancer-related quality of life.	3 months

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2021
• Primary Completion (Actual): April 30, 2023
• Study Completion (Actual): April 30, 2023

Study Registration Dates

• First Submitted: March 10, 2021
• First Submitted That Met QC Criteria: March 17, 2021
• First Posted (Actual): March 18, 2021

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 3, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Immunotherapy; Ablation; PD-1
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: MA-BC-Ⅱ-021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Available from the corresponding author upon reasonable request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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