A Study of SBRT Combined With Puterizumab in Intrapulmonary Metastasis From NSCLC

The Efficacy and Safety of Stereotactic Radiotherapy Combined With Puterizumab in Non Small Cell Lung Cancer With Intrapulmonary Metastasis：A Phase II Prospective Single Arm Clinical Study

This study aims to evaluate the efficacy and safety of SBRT combined with Puterizumab immunotherapy for non-small cell lung cancer with pulmonary metastases, and to determine the correlation between MRD and treatment efficacy. Through single-cell sequencing and spatial transcriptome information analysis, the underlying mechanisms will be analyzed to provide a basis for improving the new precision treatment methods for tumor immunotherapy resistance.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Small-Cell Lung Cancer
• Intervention / Treatment: Radiation: Stereotactic Body Radiation Therapy，SBRT; Drug: Puterizumab

• Study Type: Interventional
• Enrollment (Estimated): 37
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaonan Sun, Ph D; Phone Number: 8613606618387; Email: sunxiaonan@zju.edu.cn
• Study Contact Backup: Name: Xuyun Xie, MD; Phone Number: 8613989882983; Email: 3413007@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. age≥18
2. Non small cell lung cancer patients who have experienced pulmonary metastasis after PD-1 immunotherapy in the past
3. Voluntarily participate in this study and sign an informed consent form
4. The presence of evaluable size and number of pulmonary metastases on chest CT
5. There are indications for lung puncture biopsy
6. General physical condition (ECOG) 0-1
7. The laboratory test meets the following standards: white blood cell count>3.5 × 109/L, absolute value of neutrophils>1.8 × 109/L, platelet count ≥ 75 × 109/L, hemoglobin ≥ 100g/L; NR ≤ 1.5, and APTT ≤ 1.5 times the upper limit of normal value or partial prothrombin time (PT) ≤ 1.5 times the upper limit of normal value; Total bilirubin ≤ 1.25 times the upper limit of normal value; ALT and AST<5 times the upper limit of normal values; 24-hour creatinine clearance rate>50mL/min or blood creatinine<1.5 times the upper limit of normal value.

Exclusion Criteria:

1. Unable to tolerate or refuse further immunotherapy
2. Vulnerable groups, including individuals with mental illness, cognitive impairment, critically ill patients, minors, pregnant women, illiteracy, etc

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: experimental group; The enrolled subjects will receive SBRT treatment combined with Puterizumab.

Radiation: Stereotactic Body Radiation Therapy，SBRT; The enrolled subjects will receive SBRT treatment for lung metastases.The dose segmentation is 10Gy/f, with a total dose of 50Gy/5f, once every other day.; Drug: Puterizumab; Within 7-14 days after SBRT, Puterizumab should be used (dosage: recommended dosage of 200mg, intravenous infusion, infusion time of 60 minutes (± 15 minutes), once every 3 weeks (Q3W), for 6-8 months or intolerable toxicity).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
tumor response rate	The tumor response rate will evaluate the local control of lung metastases，referring to the evaluation criteria for solid tumor efficacy RECIST 1.1	From the date of enrollment until the first record of tumor progression or any cause of death (whichever comes first), evaluations will be conducted 3 weeks and every 3 months after SBRT for up to 48 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minor Residual Lesions	Using the minimal residual disease (MRD) panel for ctDNA molecular residual detection, and through ctDNA multi-node assessment, we can dynamically monitor the therapeutic efficacy and disease recurrence.	From the date of enrollment until the first record of tumor progression or any cause of death (whichever comes first), evaluations will be conducted 3 weeks and every 3 months after SBRT for up to 48 months.
progression-free survival	PFS is the time from enrollment to tumor progression or death.	From the date of enrollment until the first record of tumor progression or any cause of death (whichever comes first), evaluations will be conducted 3 weeks and every 3 months after SBRT for up to 48 months.
overall survival	OS is the time from enrollment to death due to any reason.	From the date of enrollment until the first record of tumor progression or any cause of death (whichever comes first), evaluations will be conducted 3 weeks and every 3 months after SBRT for up to 48 months.
RTOG acute radiation injury grading	Refer to the acute radiation injury grading standards of the United States Collaborative Group on Tumor Radiotherapy (RTOG)	From the date of enrollment until the first record of tumor progression or any cause of death (whichever comes first), evaluations will be conducted during the entire SBRT process and monthly after SBRT for up to 12 months.
QLQ-30 score	The quality of life will be evaluated using the QLQ-30 score.	From the date of enrollment until the first record of tumor progression or any cause of death (whichever comes first), evaluations will be conducted 3 weeks and every 3 months after SBRT for up to 48 months.
Lymphocyte subpopulation analysis	Using flow cytometry to detect the count and percentage of lymphocytes, including CD3+, CD3+, CD4+, CD3+, CD8+, CD4+/CD8+, and CD3-CD56+.	From the date of enrollment until the first record of tumor progression or any cause of death (whichever comes first), evaluations will be conducted 3 weeks and every 3 months after SBRT for up to 48 months.

Collaborators and Investigators

• Sponsor: Sir Run Run Shaw Hospital
• Investigators: Study Chair: Xiaonan Sun, Ph D, Sir Runrun Shaw Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: May 19, 2024
• First Submitted That Met QC Criteria: May 23, 2024
• First Posted (Actual): May 30, 2024

Study Record Updates

• Last Update Posted (Actual): May 30, 2024
• Last Update Submitted That Met QC Criteria: May 23, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: immunotherapy; lung cancer; radiotherapy; SBRT; single-cell sequencing; peripheral blood mononuclear cell; minimalResidual disease
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: SRRS-LCsbrt

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: After the research is completed, the statistical results will be published as an article.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No