Non-small Cell Lung Cancer Stage III
Conditions
Keywords
Non-small cell lung cancer, Immune checkpoint inhibitors, Radiotherapy, Radiation pneumonitis
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.
Interventions
RADIATIONradiotherapy
Radiotherapy techniques: Volumetric-modulated arc therapy (VMAT) and image guided radiotherapy (IGRT). Radiotherapy dose: Radical prescription dose of 60 gray (Gy) ± 10%, 2 Gy per session, once a day, 5 days a week.
Cisplatin 25 mg/m2 once per week for a total of 5-6 cycles. For participants who have not completed 4 cycles of conversion chemotherapy in combination with immunotherapy, the original chemotherapy regimen may also be used, with the total number of chemotherapy cycles not exceeding 6 cycles.
DRUGImmunotherapy
Concurrent programmed cell death 1 (PD-1) or programmed cell death L1 (PD-L1) inhibitors every 3 weeks during radiotherapy and no more than 3 doses during the course of radiotherapy.
All participants will be evaluated within 1-42 days after receiving radiation (chemotherapy). If disease progression does not occur, adjuvant therapy with a PD-1 or PD-L1 inhibitor is continued until disease progression up to 1 year.
Sponsors
Zhejiang Cancer Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| radiation pneumonitis | Within 6 months after radiation therapy | Incidence of grade 2 or higher radiation pneumonitis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| progression-free survival | 2 years | Time from enrolment to disease progression or death from any cause or censored at the last follow-up. |
| overall survival | 3 years | Time from enrolment to death or censored at the last follow-up. |
Contacts
Primary ContactXu Yujin, PhD
Outcome results
None listed