Bronchoscopic Cryoablation Combined With Chemo-Immunotherapy in NSCLC With Central Airway Obstruction (Example)

The Efficacy and Safety of Bronchoscopic Cryoablation Combined With Sintilimab Plus Platinum-based Chemotherapy as First-line Treatment for Locally Advanced or Metastatic NSCLC With Central Airway Obstruction: A Phase II Study

This study aimed to evaluate the efficacy and safety of bronchoscopic cryoablation combined with sintilimab plus platinum-based chemotherapy as First-line Treatment for locally advanced or metastatic NSCLC with central airway obstruction.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Sintilimab, Nab-Paclitaxel, and Carboplatin

Detailed Description

This is a prospective interventional clinical study to evaluate the efficacy and safety of bronchoscopic cryoablation combined with sintilimab plus platinum-based chemotherapy as First-line Treatment for locally advanced or metastatic Non-small Cell Lung Cancer with central airway obstruction.

Approximately 39 patients with locally advanced or metastatic NSCLC and central airway obstruction, without EGFR-sensitive mutations (19del, L858R, and T790M), were enrolled and treated with bronchoscopic cryoablation combined with Sintilimab, Nab-Paclitaxel, and Carboplatin until disease progression, intolerable toxicity, or meeting the criteria for discontinuation of the trial drug.

The primary endpoint is the investigator-assessed objective response rate (ORR) of airway tumors. Secondary endpoints include the pathological response rate (PRR) of airway tumors, disease control rate (DCR), improvement rate of FEV1, duration of response (DOR) for airway tumors, progression-free survival (PFS), overall survival (OS), quality of life assessment, and safety. Recruitment for the study is expected to begin in mainland China around October 2024, with the trial anticipated to conclude in October 2027.

• Study Type: Interventional
• Enrollment (Estimated): 39
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yongchang Zhang; Phone Number: +8613873123436; Email: zhangyongchang@csu.edu.cn

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China
      • Hunan Cancer Hospital
      • Contact: Yongchang Zhang, MD; Phone Number: 13873123436; Email: zhangyongchang@csu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Understand the requirements and contents of the clinical trial and provide a signed and dated informed consent form.
• Age≥18 years and≤80 years.
• Histologically or cytologically confirmed and documented locally advanced or metastatic non-small cell lung cancer (NSCLC) without prior systemic therapy and EGFR-sensitive mutations (19del, L858R and T790M).
• Presence of a palliative treatment lesion in the central airway that is amenable to ablation, endoscopically assessed to be≥1/3 obstruction, such as primary or metastatic malignancy to the trachea, main bronchi, intermediate bronchi, or segmental bronchi. corresponding respiratory symptoms or obstructive pneumonia is permission to be included.
• Eastern Cooperative Oncology Group (ECOG) ： 0-2.
• Predicted survival ≥ 12 weeks.
• Adequate bone marrow hematopoiesis and organ function (cardiac function, hepatic, and renal function).
• Presence of measurable lesions according to RECIST 1.1 criteria.
• Subjects with stable brain metastases may be included in the study.

Exclusion Criteria:

• Histological diagnosis of small cell, large cell lung cancer; mixed tumors will be classified based on the primary cell type; if the primary component is small cell, large cell, or neuroendocrine carcinoma, the subject will not be eligible for enrollment; however, mixed adenocarcinoma-squamous cell carcinoma is acceptable. Subjects with driver gene mutations are generally not eligible for enrollment.
• Malignant central airway obstruction with acute dyspnea or severe life-threatening symptoms of malignant airway stenosis, or assessed by the investigator to be unable to tolerate subsequent treatment; extrinsic airway compression; large pleural effusion, severe coughing, massive hemoptysis, dyspnea, or inability to cooperate; severely impaired lung function with a maximal voluntary ventilation (MVV) < 39% or inability to ambulate.
• Prior systemic therapy for locally or metastatic disease.
• Uncorrectable coagulation disorders, severe bleeding tendencies, platelet count < 50 *10^9/L, or severe coagulation dysfunction.
• Presence of symptomatic brain metastases.
• Known severe hypersensitivity to anti-PD-1 monoclonal antibodies or similar drugs (allergic reactions with CTCAE≥ grade 3 toxicity).
• Subjects with persistent or active infection, including but not limited to hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV).
• Any concurrent malignancy other than basal cell carcinoma or cervical carcinoma in situ. (Patients with a history of malignant tumors but with no evidence of disease for≥ 3 years may be included ).
• Women who are breastfeeding or pregnant.
• Other conditions assessed by the investigator to be unsuitable for participation in the study.

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: group 1; Bronchial endoscopic cryoablation	Drug: Sintilimab, Nab-Paclitaxel, and Carboplatin; Cryoablation received at least 2 or more depending on the mass, with 2-3 cycles；Sintilimab 200 mg Q3W plus Nab-Paclitaxel 260mg / m2(Day 1) Q3W + carboplatin AUC 4.25 or 5 (Day 1) Q3W, 4 cycles，until 24 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate of Airway Tumor	The ORR for Objective response of airway tumors after cryoablation combined with immunochemotherapy was evaluated according to the investigator's Solid Tumor Response Assessment Criteria (RECIST) version 1.1, defined as the proportion of subjects who were evaluated for complete response (CR) + partial response (PR) to airway tumors after the first documented treatment	Time from first dose to last dose, or up to 24 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Response Rate of Airway Obstruction	The pathologic response rate of airway tumors obstruction in patients treated with cryoablation combined with immunochemotherapy was evaluated according to the investigator which was defined as the proportion of subjects with endoscopically assessed airway pathologic residual tumors ≤10% after treatment recorded for the first or last time after cryoablation	Time from first dose to last dose, or up to 24 month
Airway Obstruction Response Control Rate	The DCR for airway tumors obstruction in patients treated with cryoablation combined with immunochemotherapy was assessed according to the investigator's RECIST 1.1, defined as the proportion of subjects evaluated for complete (CR) + partial response (PR) and stable SD for intraairway tumors after the first recorded treatment	Time from first subject dose to study completion, or up to 36 month
FEV1R improvement rate of airway obstruction	Calculated according to the subjects' pulmonary function measures assessed by the investigator: FEV1 (post-treatment) -FEV1 (pre-treatment)/FEV1 (pre-treatment) *100%	Time from first subject dose to study completion, or up to 36 month
Airway Obstruction Response Duration	The duration of response in subjects with CR or PR was assessed according to the Solid Tumor Response Assessment Criteria (RECIST) version 1.1 developed by the investigators, defined as the time from the first recorded evaluated airway tumor CR or PR to airway disease progression or death	Time from first subject dose to study completion, or up to 36 month
Progression-free survival	Progression-free survival of patients treated with cryoablation plus immunochemotherapy was assessed according to the Investigator Response Evaluation criteria (RECIST) version 1.1, defined as the duration of first documented disease progression or death from any cause	Time from first subject dose to study completion, or up to 36 month
Overall survival	To assess overall survival, it was defined as the first dose at which the subject died from any cause	Time from first subject dose to study completion, or up to 36 month
Adverse events	Number of participants with adverse events (AEs) according to CTCAE 5.0	Time from first subject dose to study completion, or up to 36 month
Life quality score	Score according to EORTC QLQ-L30+QLQ-LC13 table	Time from first subject dose to study completion, or up to 36 month

Collaborators and Investigators

• Sponsor: Hunan Province Tumor Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 15, 2024
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): May 31, 2029

Study Registration Dates

• First Submitted: August 27, 2024
• First Submitted That Met QC Criteria: September 17, 2024
• First Posted (Estimated): September 19, 2024

Study Record Updates

• Last Update Posted (Estimated): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 17, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency; Airway Obstruction; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: 20240827

Drug and device information, study documents

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