Phase II Trial: Low-Dose Radiation + SBRT + Sintilimab + Chemotherapy vs. Sintilimab + Chemotherapy in Advanced Squamous Cell Lung Cancer

Study Overview
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Brief Summary
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This is a randomized, controlled, open-label, multicenter phase II clinical trial comparing the efficacy and safety of low-dose radiation therapy and stereotactic body radiation therapy combined with PD-1 inhibitor (sintilimab) and standard platinum-based doublet chemotherapy versus PD-1 inhibitor (sintilimab) combined with standard platinum-based doublet chemotherapy as first-line treatment in patients with advanced squamous cell lung cancer. There will be 68 subjects in the experimental group and 68 subjects in the control group, with a total of 136 subjects.

Detailed Description
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This is a randomized, controlled, open-label, multicenter phase II clinical trial comparing the efficacy and safety of low-dose radiation therapy and stereotactic body radiation therapy combined with PD-1 inhibitor (sintilimab) and standard platinum-based doublet chemotherapy versus PD-1 inhibitor (sintilimab) combined with standard platinum-based doublet chemotherapy as first-line treatment in patients with advanced squamous cell lung cancer. Patients with previously untreated, advanced or metastatic (stage IV) squamous cell lung cancer who have signed informed consent will be screened for eligibility. Qualified subjects who meet the inclusion criteria will be randomly assigned at a 1:1 ratio to the experimental group (radiation therapy plus sintilimab and chemotherapy) or the control group (sintilimab plus chemotherapy). Based on sample size estimation according to statistical hypotheses, there will be 68 subjects in the experimental group and 68 subjects in the control group, with a total of 136 subjects. Subjects in the experimental group will receive radiation therapy. Within 1 week after radiation therapy, they will receive treatment with sintilimab combined with standard platinum-based doublet chemotherapy. Chemotherapy combined with immunotherapy will consist of a total of 4 cycles. Patients will subsequently receive maintenance therapy with sintilimab. Subjects in the control group will receive treatment with sintilimab combined with standard platinum-based doublet chemotherapy, consisting of a total of 4 cycles. Patients will subsequently receive maintenance therapy with sintilimab. The primary efficacy endpoint of this study is the progression-free survival (PFS), as assessed by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

Official Title
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Low-dose Radiation Therapy and Stereotactic Body Radiation Therapy Combined With PD-1 Inhibitor Sintilimab and Chemotherapy Versus PD-1 Inhibitor Combined With Chemotherapy as First-line Treatment for Patients With Advanced Squamous Cell Lung Cancer: A Randomized, Phase II Multicenter Clinical Trial

Conditions
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Advanced Lung Squamous Cell Carcinoma

Intervention / Treatment
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* Radiation: low-dose radiation therapy and stereotactic body radiation therapy
* Drug: chemotherapy
* Drug: Sintilimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old and ≤ 75 years old; Histologically or cytologically confirmed squamous cell lung cancer, imaging confirmed metastatic disease (stage IV); According to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1), there is at least one imaging measurable lesion; Enough to provide quality control qualified tumor tissue or cell wax blocks to detect PD-L1 expression; Have not received any systemic anti-tumor treatment for metastatic disease in the past; Exclusion Criteria: The pathology is small cell lung cancer (SCLC), including lung cancer mixed with SCLC and non-small cell lung cancer (NSCLC)； The pathology is lung adenocarcinoma, including lung cancer mixed with lung adenocarcinoma and lung squamous cell carcinoma; EGFR gene sensitive mutation or ALK fusion positive or ROS1 fusion positive; Previously received the following therapies: anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or another drug that stimulates or synergistically inhibits T cell receptors; Pregnant or lactating women;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radiotherapy combined with sintilimab and chemotherapy<br>Subjects received radiotherapy (SBRT+LDRT). Sintilimab combined with standard platinum-containing double-drug chemotherapy was performed within 1 week after the end of radiotherapy. | Radiation: low-dose radiation therapy and stereotactic body radiation therapy<br>* Patients will receive radiation therapy.<br>* Other names: RT;Drug: chemotherapy<br>* Patients will receive sintilimab combined with standard platinum-based doublet chemotherapy for a total of 4 cycles. Patients subsequently received maintenance treatment with sintilimab, and continued treatment until disease progression (PD), intolerable toxicity, withdrawal of informed consent, initiation of other anti-tumor treatments, death, or other circumstances that should stop treatment as specified in the protocol. Whichever occurs first. The maximum treatment time with sintilimab is 24 months (or 35 cycles).<br>* Other names: standard platinum-containing double-drug chemotherapy;Drug: Sintilimab<br>* Patients will receive sintilimab combined with standard platinum-based doublet chemotherapy for a total of 4 cycles. Patients subsequently received maintenance treatment with sintilimab, and continued treatment until disease progression (PD), intolerable toxicity, withdrawal of informed consent, initiation of other anti-tumor treatments, death, or other circumstances that should stop treatment as specified in the protocol. Whichever occurs first. The maximum treatment time with sintilimab is 24 months (or 35 cycles).<br>|
| Active Comparator: Sintilimab+Chemotherapy<br>Subjects received sintilimab combined with standard platinum-based doublet chemotherapy for a total of 4 cycles. | Drug: chemotherapy<br>* Patients will receive sintilimab combined with standard platinum-based doublet chemotherapy for a total of 4 cycles. Patients subsequently received maintenance treatment with sintilimab, and continued treatment until disease progression (PD), intolerable toxicity, withdrawal of informed consent, initiation of other anti-tumor treatments, death, or other circumstances that should stop treatment as specified in the protocol. Whichever occurs first. The maximum treatment time with sintilimab is 24 months (or 35 cycles).<br>* Other names: standard platinum-containing double-drug chemotherapy;Drug: Sintilimab<br>* Patients will receive sintilimab combined with standard platinum-based doublet chemotherapy for a total of 4 cycles. Patients subsequently received maintenance treatment with sintilimab, and continued treatment until disease progression (PD), intolerable toxicity, withdrawal of informed consent, initiation of other anti-tumor treatments, death, or other circumstances that should stop treatment as specified in the protocol. Whichever occurs first. The maximum treatment time with sintilimab is 24 months (or 35 cycles).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival (PFS) | Investigator assessed PFS according to RECIST v1.1. Progression free survival is defined as time of enrollment to first evidence of progressive disease. | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-month PFS rate | The 6-month PFS rate is defined as the proportion of patients who did not experience disease progression or death from any cause at the time of 6 months. | From date of randomization to 6 months. | 
| 1-year PFS rate | The 1-year PFS rate is defined as the proportion of patients who did not experience disease progression or death from any cause at the time of 1 year. | From date of randomization to 1 years. | 
| overall survival(OS) | OS is defined as the time from randomization to the death of the subject from any cause. | From date of randomization to the time when the subject died from any cause, assessed up to 36 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SBRT, Immunotherapy, LDRT, Lung Squamous Cell Carcinoma