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

NCT02623595 | Withdrawn Phase 2 DMC

• 1 other identifier: CHX-65
• Study Type: interventional
• Target: N/A
• 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) is safe, effective in the treatment of stage IV NSCLC patients who failed in second-line chemotherapy.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

non-small cell lung cancer; Granulocyte-Macrophage Colony-Stimulating Factor; Stereotactic body radiotherapy; abscopal effect; safety; immunotherapy

Outcome Measures

Primary Outcomes (1)

• abscopal effect rate

  at the time point of 4 weeks after completion of rhGM-CSF

Secondary Outcomes (7)

• overall survival

  2 years

• Incidence of Adverse events

  2 years

• progression free survival

  2 years

• objective response rate

  2 years

• abscopal effect rate

  at the time point of 2 months after completion of rhGM-CSF

Other Outcomes (2)

• Total T cells count in peripheral blood

  pre-treatment,1, 2, 3, 6, 12 months after completion of rhGM-CSF

• Absolute number of CD4+T, CD8+T and regulatory T cells

  pre-treatment,1, 2, 3, 6, 12 months after completion of rhGM-CSF

Study Arms (1)

SBRT+GM-CSF

EXPERIMENTAL

Metastasis lesion will be treated with a SBRT of 50Gy/5F from day 1 to day 5 in a cycle of 21 days.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.

Radiation: Stereotactic body radiotherapy; Drug: rhGM-CSF

Interventions

Stereotactic body radiotherapy RADIATION

A type of radiation therapy

Also known as: SBRT, SABR

SBRT+GM-CSF

rhGM-CSF DRUG

Immune modulating agents

Also known as: Recombined human granulocyte-macrophage colony stimulating factor

SBRT+GM-CSF

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: 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.
• 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 and its accessories.
• Contraindications to GM-CSF treatment.
• Patients with unilateral lung.

Sponsors & Collaborators

• Wuhan University: lead
• Tongji Hospital: collaborator
• Hubei Cancer Hospital: collaborator

Study Sites (1)

Zhongnan hospital of Wuhan university

Wuhan, Hubei, 430071, China

Location

Related Publications (10)

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  PMID: 26028407 BACKGROUND

• Daly ME, Monjazeb AM, Kelly K. Clinical Trials Integrating Immunotherapy and Radiation for Non-Small-Cell Lung Cancer. J Thorac Oncol. 2015 Dec;10(12):1685-93. doi: 10.1097/JTO.0000000000000686.

  PMID: 26484629 BACKGROUND

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• 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. doi: 10.1006/cimm.1995.1211.

  PMID: 7553889 BACKGROUND

• 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.

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• Hiniker SM, Chen DS, Reddy S, Chang DT, Jones JC, Mollick JA, Swetter SM, Knox SJ. A systemic complete response of metastatic melanoma to local radiation and immunotherapy. Transl Oncol. 2012 Dec;5(6):404-7. doi: 10.1593/tlo.12280. Epub 2012 Dec 1.

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  PMID: 26095785 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Radiosurgery; regramostim

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Conghua Xie, MD, PhD

  Zhongnan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor,MD,PhD,Director of Department of Radiation and Medical Oncology,Zhongnan Hospital

Study Record Dates

• First Submitted: November 23, 2015
• First Posted: December 7, 2015
• Study Start: May 1, 2016
• Primary Completion: May 1, 2019
• Study Completion: November 1, 2019
• Last Updated: October 15, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)