Chemotherapy Combination With Local Radiotherapy and rhGM-CSF for Oligometastatic Stage IV NSCLC Patients

Study Overview
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Brief Summary
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The purpose of this study is to determine whether chemotherapy combination with local radiotherapy and rhGM-CSF is safe, effective in the treatment of oligometastatic stage IV NSCLC patients.

Detailed Description
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The purpose of this study is to determine whether chemotherapy combination with local radiotherapy and recombined human granulocyte-macrophage colony stimulating factor(rhGM-CSF) is safe, effective in the treatment of oligometastatic stage IV NSCLC patients who were PR or SD after first-line chemotherapy，and to observe the abscopal effect, whether the scheme can improve PFS and OS.

Official Title
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Chemotherapy Combination With Local Radiotherapy and rhGM-CSF for Oligometastatic Stage IV NSCLC Patients Without Progression After First-line Chemotherapy: a Prospective Randomized Controlled Study

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Biological: rhGM-CSF
* Drug: Pemetrexed
* Radiation: Local Radiotherapy
* Drug: Single agent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage IV NSCLC patients without clear driving genes who were PR or SD after standard first-line chemotherapy; Patients who were oligometastasis evaluated by PET-CT or other examinations after first-line chemotherapy. Eligible patients should have 2 to 5 distant metastases (at least 2 metastases were suitable for low fractionated radiotherapy). At least one distant measurable lesion outside the radiation sites. Age varied from 18 to 75 years old. ECOG performance status 0-2. Expected lifespan ≥3 months. Absolute neutrophil count (ANC) ≥1.5×109/L, Platelets ≥100×109/L, Hemoglobin ≥90 g/L. Able to understand and give written informed consent and comply with study procedures. Exclusion criteria Allergy of rhGM-CSF and its accessories. Disease of systemic immune or immune disorders. Histology confirmed small cell carcinoma or other malignant compositions in the cancer tissue. Patients with thrombotic disease or platelets ≥600×109/L Cancer history within 5 years apart from NSCLC before enrollment. Tumor related immunotherapy within 4 weeks, including but not limited to immune cell therapy, tumor vaccine therapy, Immune checkpoint therapy, and other immunomodulators (such as thymosin, lentinan) except for rhGM-CSF. The abnormality of kidney , heart or lung functions（serum creatinine, Cr>177mol/L; serum AST or ALT more than 2 times above normal limits; total bilirubin, TBIL>34mol/L）. HIV virus, hepatitis C virus or T lymphocyte virus (type1 or type 2) infection and active hepatitis or other uncontrolled infections. Women in pregnancy or lactation. Others who do not meet the inclusion criteria.

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+chemotherapy+ rhGM-CSF<br>Patients with PR or SD after first-line chemotherapy will be treated with pemetrexed on d1 (500mg/m2) or other single agent on d1, d8. Local radiotherapy dose will be> 4Gy per time（or BED >45Gy） from day 2 to day 15 in a cycle of 21 days. Subcutaneous injection of rhGM-CSF (200ug/m² per day) will be executed 24 hours after chemotherapy. Repeat in the second metastatic lesions. | Biological: rhGM-CSF<br>* rhGM-CSF is a stimulator of the growth and differentiation of hematopoietic progenitor cells committed to neutrophils, monocytes or eosinophils. rhGM-CSF can promote the maturation of dendritic cells and macrophage, increase their antigen presentation ability.<br>* Other names: Recombinant human granulocyte macrophage stimulating factor;Drug: Pemetrexed<br>* Pemetrexed (brand name Alimta) is a chemotherapy drug manufactured and marketed by Eli Lilly and Company. Its indications are the treatment of pleural mesothelioma and non-small cell lung cancer.<br>Radiation: Local Radiotherapy<br>* Radiotherapy promotes the release of tumor antigen<br>* Other names: Local Radiation therapy;Drug: Single agent<br>* Other chemotherapy drugs,such as Docetaxel, gemcitabine<br>* Other names: Single agent for maintenance therapy;|
| Experimental: Single agent maintenance therapy<br>Maintenance treatment by single agent in a cycle of 21 days. | Drug: Single agent<br>* Other chemotherapy drugs,such as Docetaxel, gemcitabine<br>* Other names: Single agent for maintenance therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Progression-Free-Survival | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abscopal effect rate | Radiotherapy-induced immune-mediated tumour regression at sites distant to the irradiated field | At the time point of 4 weeks after completion of rhGM-CSF | 
| OS | Overall survival | 2 years |