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

NCT ID: NCT06031597

Last Updated: 2023-09-13

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-15
• Study Completion Date: 2025-12-31

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.

Conditions

Non-small Cell Lung Cancer Stage III

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A: concurrent chemoradiotherapy combined with ICIs

For performance status (PS)=0-1 and both lungs V20≤20%, mean lung dose (MLD)≤11 gray(Gy), then the patient should be treated with concurrent chemo-radiotherapy and immunotherapy, and immunotherapy should be given after chemo-radiotherapy to maintain up to 1 year. Participants eligible for enrollment will receive radiotherapy within 8 weeks of the end of chemotherapy combined with Immune checkpoint inhibitors (ICIs) at a radical prescribed dose of 60 Gy ± 10% at 2 Gy once daily for 5 days per week. The chemotherapy regimen will be cisplatin at a dose of 25 mg/m2 once a week for 5-6 cycles. Marketed programmed cell death 1 (PD-1) or programmed cell death L1 (PD-L1) inhibitors are chosen as immunotherapy agents. Immunotherapy will be given every 3 weeks, with no more than 3 cycles of immunotherapy during radiotherapy. The dosage is recommended according to the drug insert.

Group Type: EXPERIMENTAL

radiotherapy

Intervention Type: RADIATION

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.

Platinum-Based Drug

Intervention Type: 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

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Cohort B: concurrent radiotherapy combined with ICIs

For PS=0-1 and 20%\<both lungs V20≤25% or 11Gy\<MLD≤13Gy, radiotherapy alone combined with concurrent immunotherapy, followed by immunotherapy up to 1 year. Participants eligible for enrollment will receive radiotherapy within 8 weeks of the end of chemotherapy combined with ICIs at a radical prescribed dose of 60 Gy ± 10% at 2 Gy once daily for 5 days per week. Marketed PD-1 or PD-L1 inhibitors are chosen as immunotherapy agents. Immunotherapy will be given every 3 weeks, with no more than 3 cycles of immunotherapy during radiotherapy. The dosage is recommended according to the drug insert.

Group Type: EXPERIMENTAL

radiotherapy

Intervention Type: RADIATION

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.

Immunotherapy

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Cohort C: radiotherapy

For PS=2 or 25%\<both lungs V20≤30% or 13Gy\<MLD≤17Gy, radiotherapy alone, followed by immunotherapy for up to 1 year. Participants eligible for enrollment will receive radiotherapy within 8 weeks of the end of chemotherapy combined with ICIs at a radical prescribed dose of 60 Gy ± 10% at 2 Gy once daily for 5 days per week. Marketed PD-1 or PD-L1 inhibitors are chosen as immunotherapy agents. The dosage is recommended according to the drug insert.

Group Type: EXPERIMENTAL

radiotherapy

Intervention Type: RADIATION

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.

Immunotherapeutic Agent

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: RADIATION

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Cisplatin; Nivolumab; Atezolizumab; Durvalumab; Pembrolizumab; Tislelizumab; Sugemalimab; Sintilimab; Camrelizumab; Nivolumab; Atezolizumab; Durvalumab; Pembrolizumab; Tislelizumab; Sugemalimab; Sintilimab; Camrelizumab

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zhejiang Cancer Hospital

OTHER

Sponsor Role: lead

Responsible Party

Xu Yujin, MD

Chief Physician, Department of Thoracic Radiotherapy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xu Yujin, PhD

Role: STUDY_DIRECTOR

Zhejiang Cancer Hospital

Central Contacts

Xu Yujin, PhD

Role: CONTACT

xuyj@zjcc.org.cn

86-13858037993

Other Identifiers

IRB-2023-700(IIT)

Identifier Type: -

Identifier Source: org_study_id