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

Carcinoma, Non-Small-Cell Lung Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02623595
• Other study ID #: CHX-65
• Status: Withdrawn
• Phase: Phase 2
• Start date: May 2016
• Est. completion date: November 2019

Study information

• Verified date: October 2018
• Source: Wuhan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 2019
• Est. primary completion date: May 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Radiation:
• Stereotactic body radiotherapy
A type of radiation therapy

Drug:
• rhGM-CSF
Immune modulating agents

Locations

Country	Name	City	State
China	Zhongnan hospital of Wuhan university	Wuhan	Hubei

Sponsors (3)

Lead Sponsor	Collaborator
Wuhan University	Hubei Cancer Hospital, Tongji Hospital

Country where clinical trial is conducted

China, 

References & Publications (10)

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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. — View Citation

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Slovin SF, Higano CS, Hamid O, Tejwani S, Harzstark A, Alumkal JJ, Scher HI, Chin K, Gagnier P, McHenry MB, Beer TM. Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: results from an open-label, multicenter phase I/II study. Ann Oncol. 2013 Jul;24(7):1813-21. doi: 10.1093/annonc/mdt107. Epub 2013 Mar 27. — View Citation

Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28;366(26):2443-54. doi: 10.1056/NEJMoa1200690. Epub 2012 Jun 2. — View Citation

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. — View Citation

Yokouchi H, Yamazaki K, Chamoto K, Kikuchi E, Shinagawa N, Oizumi S, Hommura F, Nishimura T, Nishimura M. Anti-OX40 monoclonal antibody therapy in combination with radiotherapy results in therapeutic antitumor immunity to murine lung cancer. Cancer Sci. 2008 Feb;99(2):361-7. doi: 10.1111/j.1349-7006.2007.00664.x. Epub 2008 Jan 14. — View Citation

Younes E, Haas GP, Dezso B, Ali E, Maughan RL, Kukuruga MA, Montecillo E, Pontes JE, Hillman GG. Local tumor irradiation augments the response to IL-2 therapy in a murine renal adenocarcinoma. Cell Immunol. 1995 Oct 15;165(2):243-51. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Total T cells count in peripheral blood	To assess the absolute number of T cells in per milliliter peripheral blood pre- and post-therapy.	pre-treatment,1, 2, 3, 6, 12 months after completion of rhGM-CSF
Other	Absolute number of CD4+T, CD8+T and regulatory T cells	To assess ratio of effector T cells: regulatory T cells in per milliliter peripheral blood pre- and post-therapy.	pre-treatment,1, 2, 3, 6, 12 months after completion of rhGM-CSF
Primary	abscopal effect rate		at the time point of 4 weeks after completion of rhGM-CSF
Secondary	overall survival		2 years
Secondary	Incidence of Adverse events	All adverse events will be recorded	2 years
Secondary	progression free survival		2 years
Secondary	objective response rate		2 years
Secondary	abscopal effect rate		at the time point of 2 months after completion of rhGM-CSF
Secondary	Incidence of treatment-related adverse events	All treatment-related adverse events will be recorded	2 years
Secondary	Incidence of immune-related adverse events	All Immune-related adverse events will be recorded	2 years

External Links

•   Official website