SBRT Combination With rhGM-CSF and Tα1 for Stage IV NSCLC Patients Who Failed in Second-line Chemotherapy

NCT02976740 | Unknown Phase 2

• 1 other identifier: KYZ2016-006
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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) and Thymosin Alpha 1 is safe, effective in the treatment of stage IV NSCLC patients who failed in second-line chemotherapy.

Conditions

Lung Cancer Metastatic

Keywords

lung cancer; SBRT; rhGM-CSF; Thymosin Alpha 1

Outcome Measures

Primary Outcomes (1)

• abscopal effect rate

  at the time point of 4 weeks after completion of the combined treatment

Secondary Outcomes (4)

• 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

  4 weeks after completion of the combined treatment

• Incidence of immune-related adverse events

  1 year after completion of the combined treatment

Study Arms (1)

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.

Radiation: SBRT; Drug: Immunological Agent; Drug: Immunological Factors

Interventions

SBRT RADIATION

Stereotactic body radiotherapy A type of radiation therapy to the Metastasis lesion

Also known as: SABR

SBRT+GM-CSF+Tα1

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.

Also known as: rh GM-CSF

SBRT+GM-CSF+Tα1

Immunological Factors DRUG

Thymosin Alpha 1(1.6mg Biw)will be executed from the fist Week to the 12th Weeks.

Also known as: Tα1

SBRT+GM-CSF+Tα1

Eligibility Criteria

• Age: 17 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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, Including diabetes.
• 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/Tα1 and its accessories.
• Contraindications to GM-CSF/Tα1 treatment.
• Patients with unilateral lung.

Sponsors & Collaborators

• The First Affiliated Hospital of Xiamen University: lead

Study Sites (1)

First affiliated Hospital of Xiamen University

Xiamen, Fujian, 361000, China

RECRUITING

Related Publications (10)

• 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.

  PMID: 25754329 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.

  PMID: 19573801 BACKGROUND

• Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011 Dec 21;480(7378):480-9. doi: 10.1038/nature10673.

  PMID: 22193102 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.

  PMID: 23462419 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.

  PMID: 23863633 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.

  PMID: 22700877 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.

  PMID: 16636135 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.

  PMID: 22397654 BACKGROUND

• 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.

  PMID: 26095785 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.

  PMID: 24563870 RESULT

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Adjuvants, Immunologic; Immunologic Factors

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Central Study Contacts

Deng Chong, MD

CONTACT

86-05922139531; dengchongxm@163.com

Lin Qin, MD/PhD

CONTACT

86-05922139531; linqin03@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2016
• First Posted: November 29, 2016
• Study Start: November 1, 2016
• Primary Completion: June 1, 2019
• Study Completion: December 1, 2019
• Last Updated: November 29, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)