Clinical trial NCT02623595: A Study of SBRT in Combination With rhGM-CSF for Stage IV NSCLC Patients Who Failed in Second-line Chemotherapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: non-small cell lung cancer
Granulocyte-Macrophage Colony-Stimulating Factor
Stereotactic body radiotherapy
abscopal effect
safety
immunotherapy
Lead sponsor: Wuhan University
Sponsor class: OTHER
Collaborators: name: Tongji Hospital
name: Hubei Cancer Hospital
First posted: 2015-12-07
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Histologically proven non-small-cell lung cancer.
2. Stage IV according to UICC stage system(version 7,2009).
3. Progression after standard second-line chemotherapy.
4. At least Three evaluable lesions among which at least two must be suitable for SBRT.
5. ECOG performance status 0-2.
6. Expected lifespan ≥3 months.
7. 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.
8. Female subjects must have a negative urine or serum pregnancy test within 72 hours prior to taking study drug if of childbearing potential.
9. Able to understand and give written informed consent and comply with study procedures.

Exclusion criteria:

1. 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.
2. 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.
3. 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.
4. Human immunodeficiency virus (HIV) infection.
5. Women in pregnancy or lactation .
6. Medicine abusers(including alcohol, drugs or other addictive drugs abusers).
7. Patients with mental illness, considered as "can't fully understand the issues of this research".
8. Cancer history within 5 years apart from NSCLC before enrollment.
9. Histologically confirmed small cell carcinoma or other non NSCLC compositions in the cancer tissue.
10. Cancer treatment within 4 weeks, including but not limited to palliative surgery ,radiotherapy, chemotherapy and target therapy.
11. 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.
12. Allergy of rhGM-CSF and its accessories.
13. Contraindications to GM-CSF treatment.
14. Patients with unilateral lung.

Primary outcomes:
measure: abscopal effect rate
timeFrame: at the time point of 4 weeks after completion of rhGM-CSF
Secondary outcomes:
measure: overall survival
timeFrame: 2 years
measure: Incidence of Adverse events
timeFrame: 2 years
measure: progression free survival
timeFrame: 2 years
measure: objective response rate
timeFrame: 2 years
measure: abscopal effect rate
timeFrame: at the time point of 2 months after completion of rhGM-CSF
measure: Incidence of treatment-related adverse events
timeFrame: 2 years
measure: Incidence of immune-related adverse events
timeFrame: 2 years
Other outcomes:
measure: Total T cells count in peripheral blood
timeFrame: pre-treatment,1, 2, 3, 6, 12 months after completion of rhGM-CSF
measure: Absolute number of CD4+T, CD8+T and regulatory T cells
timeFrame: pre-treatment,1, 2, 3, 6, 12 months after completion of rhGM-CSF
Locations:
city: Wuhan
country: China
facility: Zhongnan hospital of Wuhan university
state: Hubei
Study officials:
affiliation: Zhongnan Hospital
name: Conghua Xie, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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