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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) and Thymosin Alpha 1 is safe, effective in the treatment of stage IV NSCLC patients who failed in second-line chemotherapy.
Metastasis lesion of stage IV NSCLC will be treated with a SBRT of 50Gy/4-10F from day 1 to day 14 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.Thymosin Alpha 1(1.6mg Biw) will be Subcutaneous injection from the fist week to the 12th weeks, 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SBRT+GM-CSF+Tα1 | Experimental | Metastasis lesion will be treated with a SBRT of 50Gy/4-10F from day 1 to day 10 . Subcutaneous injection of Immunological Agent- 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. Subcutaneous injection of another Immunological Factors Thymosin Alpha 1(1.6mg Biw)will be executed from the fist WEEK to the 12th Weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SBRT | Radiation | Stereotactic body radiotherapy A type of radiation therapy to the Metastasis lesion |
|
| Measure | Description | Time Frame |
|---|---|---|
| abscopal effect rate | at the time point of 4 weeks after completion of the combined treatment |
| Measure | Description | Time Frame |
|---|---|---|
| overall survival | 1 year after completion of the combined treatment | |
| Incidence of Adverse events | 1 year after completion of the combined treatment | |
| objective response rate |
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Inclusion Criteria: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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Deng Chong, MD | Contact | 86-05922139531 | dengchongxm@163.com | |
| Lin Qin, MD/PhD | Contact | 86-05922139531 | linqin03@163.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| First affiliated Hospital of Xiamen University | Recruiting | Xiamen | Fujian | 361000 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25754329 | Background | Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, Benci JL, Xu B, Dada H, Odorizzi PM, Herati RS, Mansfield KD, Patsch D, Amaravadi RK, Schuchter LM, Ishwaran H, Mick R, Pryma DA, Xu X, Feldman MD, Gangadhar TC, Hahn SM, Wherry EJ, Vonderheide RH, Minn AJ. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015 Apr 16;520(7547):373-7. doi: 10.1038/nature14292. Epub 2015 Mar 9. | |
| 19573801 |
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| ID | Term |
|---|---|
| D008175 | Lung Neoplasms |
| ID | Term |
|---|---|
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D000276 | Adjuvants, Immunologic |
| D007155 | Immunologic Factors |
| ID | Term |
|---|---|
| D045505 | Physiological Effects of Drugs |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
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| Immunological Agent | Drug | 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. |
|
|
| Immunological Factors | Drug | Thymosin Alpha 1(1.6mg Biw)will be executed from the fist Week to the 12th Weeks. |
|
|
| 4 weeks after completion of the combined treatment |
| Incidence of immune-related adverse events | 1 year after completion of the combined treatment |
| Background |
| Formenti SC, Demaria S. Systemic effects of local radiotherapy. Lancet Oncol. 2009 Jul;10(7):718-26. doi: 10.1016/S1470-2045(09)70082-8. |
| 22193102 | Background | Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011 Dec 21;480(7378):480-9. doi: 10.1038/nature10673. |
| 23462419 | Background | Zeng J, See AP, Phallen J, Jackson CM, Belcaid Z, Ruzevick J, Durham N, Meyer C, Harris TJ, Albesiano E, Pradilla G, Ford E, Wong J, Hammers HJ, Mathios D, Tyler B, Brem H, Tran PT, Pardoll D, Drake CG, Lim M. Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas. Int J Radiat Oncol Biol Phys. 2013 Jun 1;86(2):343-9. doi: 10.1016/j.ijrobp.2012.12.025. Epub 2013 Feb 22. |
| 23863633 | Background | Kalbasi A, June CH, Haas N, Vapiwala N. Radiation and immunotherapy: a synergistic combination. J Clin Invest. 2013 Jul;123(7):2756-63. doi: 10.1172/JCI69219. Epub 2013 Jul 1. |
| 22700877 | Background | Suzuki Y, Mimura K, Yoshimoto Y, Watanabe M, Ohkubo Y, Izawa S, Murata K, Fujii H, Nakano T, Kono K. Immunogenic tumor cell death induced by chemoradiotherapy in patients with esophageal squamous cell carcinoma. Cancer Res. 2012 Aug 15;72(16):3967-76. doi: 10.1158/0008-5472.CAN-12-0851. Epub 2012 Jun 14. |
| 16636135 | Background | Reits EA, Hodge JW, Herberts CA, Groothuis TA, Chakraborty M, Wansley EK, Camphausen K, Luiten RM, de Ru AH, Neijssen J, Griekspoor A, Mesman E, Verreck FA, Spits H, Schlom J, van Veelen P, Neefjes JJ. Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J Exp Med. 2006 May 15;203(5):1259-71. doi: 10.1084/jem.20052494. Epub 2006 Apr 24. |
| 22397654 | Background | Postow MA, Callahan MK, Barker CA, Yamada Y, Yuan J, Kitano S, Mu Z, Rasalan T, Adamow M, Ritter E, Sedrak C, Jungbluth AA, Chua R, Yang AS, Roman RA, Rosner S, Benson B, Allison JP, Lesokhin AM, Gnjatic S, Wolchok JD. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012 Mar 8;366(10):925-31. doi: 10.1056/NEJMoa1112824. |
| 26095785 | Result | Golden EB, Chhabra A, Chachoua A, Adams S, Donach M, Fenton-Kerimian M, Friedman K, Ponzo F, Babb JS, Goldberg J, Demaria S, Formenti SC. Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumours: a proof-of-principle trial. Lancet Oncol. 2015 Jul;16(7):795-803. doi: 10.1016/S1470-2045(15)00054-6. Epub 2015 Jun 18. |
| 24563870 | Result | Golden EB, Demaria S, Schiff PB, Chachoua A, Formenti SC. An abscopal response to radiation and ipilimumab in a patient with metastatic non-small cell lung cancer. Cancer Immunol Res. 2013 Dec;1(6):365-72. doi: 10.1158/2326-6066.CIR-13-0115. |
| D008171 |
| Lung Diseases |
| D012140 | Respiratory Tract Diseases |