A Study of SBRT in Combination With rhGM-CSF for Stage IV NSCLC Patients Who Failed in Second-line Chemotherapy

Study Overview
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Brief Summary
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The purpose of this study is to determine whether stereotactic body radiotherapy (SBRT) combined with recombined human granulocyte-macrophage colony stimulating factor(rhGM-CSF) is safe, effective in the treatment of stage IV NSCLC patients who failed in second-line chemotherapy.

Detailed Description
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Metastasis lesion will be treated with a SBRT of 50Gy/5F from day 1 to day 5 in one cycle.Subcutaneous injection of human recombined granulocyte-macrophage colony stimulating factor (125ug/m² per day) will be executed from day 1 to day 14 in this cycle. Another metastasis lesion will be treated likewise concurrently with rhGM-CSF in a consecutive cycle. Efficacy evaluation,especially abscopal effect evaluation, will be conducted at the end of therapy and every month after that. Adverse events will be recorded according to NCI-CTC version 4.03.

Official Title
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A Prospective Single-arm Multi-center Phase II Study: Assessment of the Safety and Abscopal Effects of SBRT in Combination With rhGM-CSF for Stage IV NSCLC Patients Who Failed in Second-line Chemotherapy

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Radiation: Stereotactic body radiotherapy
* Drug: rhGM-CSF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven non-small-cell lung cancer. Stage IV according to UICC stage system(version 7,2009). Progression after standard second-line chemotherapy. At least Three evaluable lesions among which at least two must be suitable for SBRT. ECOG performance status 0-2. Expected lifespan ≥3 months. Stable lab values: Hematological: Absolute neutrophil count (ANC) ≥1.5×109/L, Platelets ≥100×109/L, Hemoglobin ≥9 g/dL Renal: Creatinine OR Measured or calculated creatinine clearance (CrCl) (glomerular filtration rate [GFR] can also be used in place of creatinine or CrCl) ≤1.5× the upper limit of normal (ULN) OR ≥60 mL/min for patient with creatinine levels >1.5× institutional ULN Hepatic: Total bilirubin ≤1.5×ULN OR Direct bilirubin ≤ULN for patients with total bilirubin levels >1.5×ULN, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN OR ≤5×ULN for patients with liver metastases ,globulin≥20 g/L, albumin≥30 g/L. Female subjects must have a negative urine or serum pregnancy test within 72 hours prior to taking study drug if of childbearing potential. Able to understand and give written informed consent and comply with study procedures. Exclusion criteria: Any unstable systemic disease, including active infection, uncontrolled high blood pressure, unstable angina, newly observed angina pectoris within the past 3 months, congestive heart failure (New York heart association (NYHA) class II or higher), myocardial infarction onset six months before included into the group, and severe arrhythmia, liver, kidney, or metabolic disease in need of drug therapy. Any clinical evidence suggests moderately severe chronic obstructive pulmonary disease (COPD) - [With COPD history or related risk factors, FEV1 / FVC < 70%, FEV1 < 80% estimated value, with or without chronic cough, sputum, dyspnea symptoms), active interstitial lung disease - ILD (FEV1 / FVC < 70%, FEV1 < 80% estimated value, carbon monoxide diffusion capacity in lung - DLCO < 40%, and high resolution CT (HRCT) confirmed as the diffuse pulmonary interstitial lesions] and other active pulmonary disease. Previously diagnosed with autoimmune diseases, including but not limited to systemic lupus erythematous, rheumatoid arthritis, systemic vasculitis, scleroderma, dermatomyositis, autoimmune hemolytic anemia and autoimmune liver disease, autoimmune thyroiditis. Human immunodeficiency virus (HIV) infection. Women in pregnancy or lactation . Medicine abusers(including alcohol, drugs or other addictive drugs abusers). Patients with mental illness, considered as can't fully understand the issues of this research. Cancer history within 5 years apart from NSCLC before enrollment. Histologically confirmed small cell carcinoma or other non NSCLC compositions in the cancer tissue. Cancer treatment within 4 weeks, including but not limited to palliative surgery ,radiotherapy, chemotherapy and target therapy. Tumor related immunotherapy within 1 year, including but not limited to immune cell therapy, tumor vaccine therapy, immune check-point monoclonal antibody related treatment, and cytokines treatment except for GM-CSF. Allergy of rhGM-CSF and its accessories. Contraindications to GM-CSF treatment. Patients with unilateral lung.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SBRT+GM-CSF<br>Metastasis lesion will be treated with a SBRT of 50Gy/5F from day 1 to day 5 in a cycle of 21 days.Subcutaneous injection of human recombined granulocyte-macrophage colony stimulating factor (125ug/m² per day) will be executed from day 1 to day 14 in this cycle. Another metastasis lesion will be treated likewise concurrently with rhGM-CSF in a consecutive cycle. | Radiation: Stereotactic body radiotherapy<br>* A type of radiation therapy<br>* Other names: SABR;Drug: rhGM-CSF<br>* Immune modulating agents<br>* Other names: Recombined human granulocyte-macrophage colony stimulating factor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| abscopal effect rate |  | at the time point of 4 weeks after completion of rhGM-CSF | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | 2 years | 
| Incidence of Adverse events | All adverse events will be recorded | 2 years | 
| progression free survival |  | 2 years | 
| objective response rate |  | 2 years | 
| abscopal effect rate |  | at the time point of 2 months after completion of rhGM-CSF | 
| Incidence of treatment-related adverse events | All treatment-related adverse events will be recorded | 2 years | 
| Incidence of immune-related adverse events | All Immune-related adverse events will be recorded | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-small cell lung cancer, Granulocyte-Macrophage Colony-Stimulating Factor, Stereotactic body radiotherapy, abscopal effect, safety, immunotherapy