Immune Checkpoint Inhibitors, Locally Advanced Non-small Cell Lung Cancer (NSCLC), Neoadjuvant Chemoimmunotherapy, Thoracic Radiotherapy
Conditions
Keywords
spatially fractionated radiotherapy, Locally Advanced NSCLC, Neoadjuvant Chemoimmunotherapy
Brief summary
Lattice radiation therapy (LRT) is a spatially fractionated thoracic radiotherapy technique that creates alternating high- and low-dose regions within primary lung tumors and metastatic lymph nodes to strengthen local tumor suppression and reduce radiation injury to normal thoracic organs. This study aims to evaluate the efficacy and safety of combining LRT with consolidation chemoimmunotherapy in unresectable stage III LA-NSCLC patients who show suboptimal tumor response to prior neoadjuvant chemoimmunotherapy, through a single-arm Phase II clinical trial. Patients will receive thoracic LRT delivered by a medical linear accelerator. High-dose spherical sub-targets will be contoured within the gross tumor volume of primary lung lesions and regional nodal metastases under standardized dose constraints to spare the lung, heart and esophagus. All enrolled subjects will receive sequential consolidation chemoimmunotherapy administered within one week after finishing LRT. Tumor response, treatment-related adverse events, local tumor control and long-term survival outcomes will be prospectively tracked throughout treatment and long-term follow-up.
Detailed description
This open-label, single-arm Phase II clinical trial investigates the combination of lattice radiation therapy (LRT) and subsequent consolidation chemoimmunotherapy for patients with unresectable stage III locally advanced non-small cell lung cancer who only achieved limited tumor regression after standard neoadjuvant chemoimmunotherapy induction. LRT, a spatially fractionated radiotherapy technique, generates interleaved high- and low-dose zones inside tumor tissue to enhance local anti-tumor activity while minimizing radiation toxicity to surrounding healthy chest organs. Eligible participants will complete standardized thoracic LRT targeting primary lesions and involved lymph nodes following institutional contouring rules and dose restrictions. Consolidation chemoimmunotherapy will be initiated shortly after the end of radiotherapy. The study will continuously monitor all treatment-related and immune-related adverse events, evaluate therapeutic efficacy via regular imaging scans, and collect long-term survival data. Trial results will provide clinical evidence about the clinical value and safety profile of LRT plus consolidation chemoimmunotherapy for this high-risk LA-NSCLC subgroup with insufficient response to prior neoadjuvant systemic therapy.
Interventions
RADIATIONlattice radiation therapy
Eligible stage III unresectable LA-NSCLC patients with suboptimal neoadjuvant response receive thoracic lattice radiotherapy via linear accelerator. Spherical high-dose LRT sub-targets are contoured inside primary and nodal GTV, avoiding blood vessels with 1cm margin and 1%-10% volume ratio of GTV. Standard fractional dose constraints for GTV and LRT targets are followed, with minimal radiation to heart, lung and esophagus. Brain and bone metastases get separate palliative radiotherapy, not included in thoracic LRT plan. Consolidation chemoimmunotherapy will be initiated within one week after radiotherapy completion.
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
1. Histologically confirmed unresectable stage III locally advanced non-small cell lung cancer (LA-NSCLC). 2. Received at least 2 cycles of standard neoadjuvant chemoimmunotherapy, with suboptimal tumor response verified by post-induction radiological evaluation. 3. Age ≥ 18 years old. 4. ECOG performance status of 0 or 1. 5. Adequate hematologic, hepatic and renal function to complete radiotherapy and consolidation systemic therapy. 6. Voluntarily sign written informed consent and be capable of following study-related procedures.
Exclusion criteria
1. Prior thoracic radiotherapy history. 2. Active uncontrolled autoimmune disorders or persistent severe immune-related adverse events. 3. Untreated symptomatic brain metastases. 4. Severe irreversible cardiac, pulmonary, liver or renal dysfunction that cannot tolerate combined radiotherapy and immunotherapy. 5. Pregnant or breastfeeding women. 6. Concurrent or previous other malignant tumors within 5 years, except cured basal cell skin cancer and cervical carcinoma in situ. 7. Any absolute contraindication to lattice radiation therapy or immune checkpoint inhibitor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate | From enrollment up to 12 months after the last subject completes combination therapy | Objective response rate (ORR) assessed by RECIST version 1.1, calculated as the proportion of patients achieving complete response (CR) or partial response (PR) after combination therapy. Tumor lesions will be evaluated with contrast-enhanced CT scans of chest, abdomen and pelvis. |
| Pathological complete response | From enrollment to 12 months after the last subject completes all study combination therapy | The proportion of patients achieving pathological complete response (pCR), defined as absence of viable residual tumor cells in post-treatment surgical resection specimens. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major pathological response | From enrollment up to 12 months after the last subject completes combination therapy | The proportion of patients achieving major pathological response (MPR), defined as ≤10% viable residual tumor cells in post-treatment surgical resection samples. |
| R0 resection rate | From enrollment up to 12 months after the last subject completes combination therapy | The proportion of patients who achieve complete R0 surgical resection without microscopic residual tumor margin after the assigned combination therapy. |
| Event-free survival | From enrollment up to 24 months after the last subject completes study treatment | The time interval from participant enrollment to the first documented disease event, including local recurrence, distant metastasis, disease progression, or death from any cause. |
| Incidence of treatment-related adverse events | From enrollment through 30 days after completion of all study treatment | The frequency, classification and maximum severity of all treatment-related adverse events assessed in accordance with CTCAE Version 5.0. |
Countries
China
Contacts
CONTACTNingbo Liu, Doctor
Outcome results
None listed