Clinical trial NCT06031597: Radiotherapy Combined With ICIs as Treatment for LA-NSCLC After Failing Induction Immunochemotherapy
Official title: Radiotherapy Combined With Immune Checkpoint Inhibitors (ICIs) as Treatment for Locally Advanced Non-small-cell Lung Cancer After Failing Induction Immuno-chemotherapy: a Prospective, Real-world Cohort Study.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer Stage III
Keywords: Non-small cell lung cancer
Immune checkpoint inhibitors
Radiotherapy
Radiation pneumonitis
Lead sponsor: Zhejiang Cancer Hospital
Sponsor class: OTHER
First posted: 2023-09-11
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Patients with stage III non-small-cell lung cancer initially evaluated as unresectable are selected for the program, who are remained unresectable after 2-4 cycles of conversion chemotherapy combined with immune checkpoint inhibitors. Investigators will stratify the treatment according to different performance status scores and radiotherapy plan bi-lung receptor volume to evaluate the safety and efficacy of immunotherapy followed by combined radiotherapy.

Detailed description: This is a prospective, real-world cohort study, which aimed to evaluate the safety and efficacy of immunotherapy followed by combined radiotherapy. Participants will be selected and entered into three different cohorts according to different performance status(PS) scores and radiotherapy schedules based on the amount of bilateral lungs treated. Cohort A: PS=0-1 and bilateral lung V20≤20%, mean lung dose(MLD)≤11 gray(Gy), radiotherapy and immunotherapy, followed by immunotherapy for up to 1 year; Cohort B: PS=0-1 and 20%\<bilateral lung V20≤25% or 11 Gy\<MLD≤13 Gy, radiotherapy combined with immunotherapy, followed by immunotherapy for up to 1 year; Cohort C: PS=2 or 25%\<bilateral V20≤30% and 3 Gy \<MLD≤ 17 Gy, radiotherapy alone, followed by immunotherapy for up to 1 year.

Eligibility criteria: Inclusion Criteria:

1. Histologically or cytologically confirmed non-small cell lung cancer
2. Presence of at least one measurable lesion according to RECIST 1.1 criteria
3. Classified as American Joint Committee on Cancer staging system, eighth edition (AJCC-8) Stage III, initially evaluated as unresectable and reevaluated as unresectable after 2-4 cycles of induction chemotherapy combined with immunotherapy
4. Age 18-75
5. Eastern Cooperative Oncology Group (ECOG) physical state score of 0-2
6. Patients with the pathologic type of adenocarcinoma should be negative for driver genes (EGFR, anaplastic lymphoma kinase, ROS1)
7. Serum hemoglobin ≥ 90 g/L, platelets ≥ 90 × 109/L, absolute neutrophil count ≥ 1.2 × 109/L
8. Serum creatinine ≤ 1.25 times upper limit of normal(ULN) or creatinine clearance ≥ 60 mL/min
9. Serum bilirubin ≤ 1.5 times ULN, (AST) and alanine aminotransferase aspartate aminotransferase (ALT) ≤ 2.5 times ULN, alkaline phosphatase ≤ 5 times ULN
10. Forced expiratory volume in one second (FEV1)\>0.8 liter
11. Normal coagulation function (Prothrombin time prolonged by no more than 3s and activated partial thromboplastin time prolonged by no more than 10s)
12. Patients signed a formal informed consent form to indicate that they understood that the study complied with the hospital's policies and ethical requirements

Exclusion Criteria:

1. The pathologic type is lung carcinoid or small cell lung cancer
2. Patients with any distant metastases
3. Grade 2 or higher unresolved toxic effects after conversion therapy (according to the Common Terminology Criteria for Adverse Events CTCAE)
4. A recent efficacy rating of PD after conversion therapy
5. Radiotherapy plan for normal lung tissue V20 \> 30%, or average lung dose MLD \> 17 Gy
6. Active or previous autoimmune disease (within the past 2 years) or history of primary immunodeficiency
7. Patients with any other previous or current malignancy, except non-melanoma skin or cervical cancer in situ
8. Any other disease or condition suggesting a contraindication to radiotherapy (e.g., active infection, within 6 months of myocardial infarction, symptomatic cardiac disease including unstable angina pectoris, congestive heart failure, or uncontrolled arrhythmias, immunosuppressive therapy)
9. Pregnant or nursing women
10. Women and men who are at risk of becoming pregnant but are unwilling to use adequate contraception
11. Evidence of hereditary bleeding disorders or coagulation disorders.

Primary outcomes:
measure: radiation pneumonitis
timeFrame: Within 6 months after radiation therapy
Secondary outcomes:
measure: progression-free survival
timeFrame: 2 years
measure: overall survival
timeFrame: 3 years
Other outcomes:
Locations:
Study officials:
affiliation: Zhejiang Cancer Hospital
name: Xu Yujin, PhD
role: STUDY_DIRECTOR
References: