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

NCT06031597 | Unknown Phase 3

• 1 other identifier: IRB-2023-700(IIT)
• Study Type: interventional
• Target: 105
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Non-small Cell Lung Cancer Stage III

Keywords

Non-small cell lung cancer; Immune checkpoint inhibitors; Radiotherapy; Radiation pneumonitis

Outcome Measures

Primary Outcomes (1)

• radiation pneumonitis

  Incidence of grade 2 or higher radiation pneumonitis.

  Within 6 months after radiation therapy

Secondary Outcomes (2)

• progression-free survival

  2 years

• overall survival

  3 years

Study Arms (3)

Cohort A: concurrent chemoradiotherapy combined with ICIs

EXPERIMENTAL

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.

Radiation: radiotherapy; Drug: Platinum-Based Drug; Drug: Immunotherapy; Drug: Immunotherapeutic Agent

Cohort B: concurrent radiotherapy combined with ICIs

EXPERIMENTAL

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.

Radiation: radiotherapy; Drug: Immunotherapy; Drug: Immunotherapeutic Agent

Cohort C: radiotherapy

EXPERIMENTAL

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.

Radiation: radiotherapy; Drug: Immunotherapeutic Agent

Interventions

radiotherapy 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.

Cohort A: concurrent chemoradiotherapy combined with ICIs; Cohort B: concurrent radiotherapy combined with ICIs; Cohort C: radiotherapy

Platinum-Based Drug 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.

Also known as: Cisplatin

Cohort A: concurrent chemoradiotherapy combined with ICIs

Immunotherapy 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.

Also known as: Nivolumab, Atezolizumab, Durvalumab, Pembrolizumab, Tislelizumab, Sugemalimab, Sintilimab, Camrelizumab

Cohort A: concurrent chemoradiotherapy combined with ICIs; Cohort B: concurrent radiotherapy combined with ICIs

Immunotherapeutic Agent 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.

Also known as: Nivolumab, Atezolizumab, Durvalumab, Pembrolizumab, Tislelizumab, Sugemalimab, Sintilimab, Camrelizumab

Cohort A: concurrent chemoradiotherapy combined with ICIs; Cohort B: concurrent radiotherapy combined with ICIs; Cohort C: radiotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• The pathologic type is lung carcinoid or small cell lung cancer
• Patients with any distant metastases
• Grade 2 or higher unresolved toxic effects after conversion therapy (according to the Common Terminology Criteria for Adverse Events CTCAE)
• A recent efficacy rating of PD after conversion therapy
• Radiotherapy plan for normal lung tissue V20 \> 30%, or average lung dose MLD \> 17 Gy
• Active or previous autoimmune disease (within the past 2 years) or history of primary immunodeficiency
• Patients with any other previous or current malignancy, except non-melanoma skin or cervical cancer in situ
• 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)
• Pregnant or nursing women
• Women and men who are at risk of becoming pregnant but are unwilling to use adequate contraception
• Evidence of hereditary bleeding disorders or coagulation disorders.

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Radiation Pneumonitis

Interventions

Radiotherapy; Cisplatin; Immunotherapy; Nivolumab; atezolizumab; durvalumab; pembrolizumab; tislelizumab; sugemalimab; sintilimab; camrelizumab; Adjuvants, Immunologic

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Lung Diseases, Interstitial; Lung Injury; Radiation Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Immunomodulation; Biological Therapy; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunologic Factors; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Xu Yujin, PhD

  Zhejiang Cancer Hospital

  STUDY DIRECTOR

Central Study Contacts

Xu Yujin, PhD

CONTACT

86-13858037993; xuyj@zjcc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician, Department of Thoracic Radiotherapy

Study Record Dates

• First Submitted: August 28, 2023
• First Posted: September 11, 2023
• Study Start: September 15, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: September 13, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share