NSCLC (Advanced Non-small Cell Lung Cancer), NSCLC (Non-small Cell Lung Cancer)
Conditions
Brief summary
The purpose of this clinical trial is to evaluate progression-free survival (PFS) of microwave ablation in combination with tislelizumab and docetaxel in patients with advanced non-small cell lung cancer (NSCLC) who have progressed following first-line immunotherapy combined with chemotherapy. Participants with advanced NSCLC who experienced disease progression after first-line immunotherapy plus chemotherapy will receive the following treatments: 1. Tislelizumab: 200 mg administered intravenously every 3 weeks (Q3W) 2. Docetaxel: 75 mg/m² administered intravenously every 3 weeks (Q3W) for 4-6 cycles 3. Microwave ablation, administered per protocol
Interventions
DRUGTislelizumab
Tislelizumab will be administered at a dose of 200 mg intravenously every 3 weeks (Q3W). Treatment will be continued according to the study protocol until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision.
DRUGDocetaxel
Docetaxel will be administered at a dose of 75 mg/m² intravenously every 3 weeks (Q3W) for a total of 4 to 6 cycles, unless discontinued earlier due to disease progression, unacceptable toxicity, or other protocol-defined criteria.
OTHERMicrowave ablation
Microwave ablation will be performed concurrently with systemic treatment. The timing and specific procedural details will be determined by the investigator according to clinical practice and patient condition. There is no predefined limit on the number of microwave ablation sessions. In general clinical practice, microwave ablation is delivered at an output power of approximately 40-60 W for a duration of 5-10 minutes per session, with 1 to 3 tumor lesions treated during a single procedure.
Sponsors
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with cytologically or histologically confirmed non-small cell lung cancer (NSCLC), classified as stage IIIB, IIIC, or IV (AJCC 9th edition) and not eligible for curative treatment. * Male or female patients aged ≥18 years who have provided written informed consent. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, with an expected survival of more than 6 months, and deemed suitable for microwave ablation by the investigator. * Patients must have previously received first-line treatment with tislelizumab in combination with chemotherapy and have documented disease progression based on imaging assessments prior to enrollment. Disease progression must occur ≥6 months after initiation of first-line tislelizumab plus chemotherapy, with or without concomitant anti-angiogenic therapy. * Adequate organ and bone marrow function, defined as follows: Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L Platelet count ≥100 × 10⁹/L Hemoglobin ≥90 g/L White blood cell count ≥3.0 × 10⁹/L Hepatic function: Total bilirubin \<1.5 × the upper limit of normal (ULN) Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), and alkaline phosphatase (ALP) ≤2.5 × ULN In patients with liver metastases: AST and ALT ≤5.0 × ULN In patients with liver and/or bone metastases: ALP ≤5.0 × ULN Renal function: Serum creatinine ≤1.5 × ULN Urine protein \<2+ on urinalysis; if baseline urine protein is ≥2+, a 24-hour urine protein ≤1.0 g is required Coagulation function: International normalized ratio (INR) ≤1.5 Activated partial thromboplastin time (aPTT) ≤1.5 × ULN * Cardiac function defined as left ventricular ejection fraction (LVEF) ≥50%. * Ability to communicate effectively with the investigator and to comply with study-related visits, treatment, laboratory tests, and other study requirements.
Exclusion criteria
Participants meeting any of the following criteria will be excluded from the study: * Diagnosis of small cell lung cancer (SCLC), including mixed small cell and non-small cell lung cancer. * Presence of symptomatic brain metastases at the start of treatment. * Concurrent participation in another interventional clinical trial for cancer treatment. * History of tracheoesophageal fistula, gastrointestinal perforation, gastrointestinal fistula, or intra-abdominal abscess within 6 months prior to treatment initiation. * Presence of severe cardiovascular or cerebrovascular disease, including but not limited to: Cerebrovascular accident (CVA), transient ischemic attack (TIA), myocardial infarction, or significant vascular disease (including but not limited to aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to randomization; Unstable angina; Heart failure classified as New York Heart Association (NYHA) class ≥ II; Mean resting corrected QT interval (QTc) \>470 ms; Any clinically significant resting electrocardiogram (ECG) rhythm, conduction, or morphological abnormalities, such as complete left bundle branch block, third-degree atrioventricular (AV) block, second-degree AV block, or PR interval \>250 ms; Any factors that increase the risk of QTc prolongation or arrhythmic events, including heart failure, electrolyte abnormalities (serum/plasma potassium \< LLN; magnesium \< LLN; calcium \< LLN), congenital long QT syndrome, family history of long QT syndrome, unexplained sudden death of a first-degree relative before the age of 40, or concomitant use of medications known to prolong the QT interval and induce torsades de pointes. * Major surgical procedures performed within 4 weeks prior to enrollment or planned during the study period. * Bleeding tendency, high risk of bleeding, or coagulation disorders, including thrombotic events within 6 months prior to randomization and/or history of hemoptysis within 3 months prior to randomization (defined as ≥2.5 mL per episode). * Presence of unhealed wounds, active gastrointestinal ulcers, or fractures (excluding healed historical fractures). * Known or suspected hypersensitivity to tislelizumab and/or any of its excipients. * Pregnant or breastfeeding women. * Women of childbearing potential or male participants who are unwilling to use effective contraception during the study and for 6 months after the last dose of study treatment. * Any other condition that, in the opinion of the investigator, would render the participant unsuitable for enrollment in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Up to 2 years | PFS was defined as the time from enrollment to the first objectively documented disease progression as assessed by the investigator per RECIST v1.1 or death from any cause, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | up to 2 years | Objective response rate is defined as the percentage of participants who had a complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 Tumor assessments included computed tomography (CT) scans or magnetic resonance imaging (MRI), with preference for CT, of the chest, abdomen, and pelvis. CR: Disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the size of target lesions and no progression of non-target lesions and no new lesions, or disappearance of all target lesions with persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits and no new lesions. |
| Overall Survival | up to 3 years | OS was defined as the time from enrollment to death from any cause. Median OS was calculated using the Kaplan-Meier method. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | up to 2 years | An adverse event is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not. The investigator assessed the severity of each AE and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03 as defined below: Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3: Severe or medically significant but not immediately life threatening. hospitalization or prolongation of hospitalization indicated; disabling; limiting selfcare activities of daily living. Grade 4: Life threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. |
Countries
China
Contacts
CONTACTTongguo Si, MD. Ph.D
Outcome results
None listed