Radiotherapy Combined With ICIs as Treatment for LA-NSCLC After Failing Induction Immunochemotherapy

Non-small Cell Lung Cancer Stage III Clinical Trial

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.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06031597
• Other study ID #: IRB-2023-700(IIT)
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: September 15, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: August 2023
• Source: Zhejiang Cancer Hospital
• Contact: Xu Yujin, PhD
• Phone: 86-13858037993
• Email: xuyj[@]zjcc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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%

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 105
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer Stage III

Intervention

Radiation:
• radiotherapy
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.

Drug:
• Platinum-Based Drug
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.
• Immunotherapy
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.
• Immunotherapeutic Agent
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Zhejiang Cancer Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	radiation pneumonitis	Incidence of grade 2 or higher radiation pneumonitis.	Within 6 months after radiation therapy
Secondary	progression-free survival	Time from enrolment to disease progression or death from any cause or censored at the last follow-up.	2 years
Secondary	overall survival	Time from enrolment to death or censored at the last follow-up.	3 years