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SBRT in Combination With Sintilimab and GM-CSF for the Treatment of Advanced NSCLC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04106180
Recruitment Status : Recruiting
First Posted : September 26, 2019
Last Update Posted : September 26, 2019
Information provided by (Responsible Party):
Zhengfei Zhu, Fudan University

Brief Summary:
This study is an open-label, multicenter, phase II single arm trial to evaluate the efficacy and safety of SBRT in combination with sintilimab and GM-CSF for the treatment of patients with advanced NSCLC.

Condition or disease Intervention/treatment Phase
NSCLC Stage IV Drug: GM-CSF Drug: Sintilimab Radiation: SBRT Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 63 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Multicenter, Phase II Single Arm Trial of SBRT in Combination With Sintilimab and GM-CSF for the Treatment of Advanced NSCLC
Estimated Study Start Date : September 30, 2019
Estimated Primary Completion Date : August 31, 2022
Estimated Study Completion Date : August 31, 2023

Arm Intervention/treatment
Experimental: SBRT + sintilimab + GM-CSF Drug: GM-CSF
Patients will receive GM-CSF 125μg/m2 daily for 14 consecutive days after completing SBRT treatment.

Drug: Sintilimab
Patients will receive Sintilimab 200 mg every 3 weeks up to 2 years after completing SBRT treatment.

Radiation: SBRT
Patients will receive SBRT for one previously unirradiated primary or metastatic lesion (size: 1-5cm). 24 Gy in 3 fractions (8Gy/Fx) administered once-daily for 3 consecutive days.
Other Name: Stereotactic body radiation therapy

Primary Outcome Measures :
  1. Overall Objective Response Rate [ Time Frame: At least 6 weeks after start of treatment ]
    ORR was defined as the proportion of participants with partial response (PR) or complete response (CR) to treatment as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Secondary Outcome Measures :
  1. Percentage of Participants With Adverse Events [ Time Frame: Two years ]
    Treatment-related adverse events were assessed and graded according to CTCAE v. 5.0.

  2. Objective Response Rate (ORR) in Non-irradiated Lesion [ Time Frame: At least 6 weeks after start of treatment ]
    Objective Response Rate (ORR) in Non-irradiated Lesion was defined as the proportion of patients with at least 30% reduction from baseline in the longest diameter of any of non-irradiated target lesions defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at any time-point from the date of treatment initiation to the date of last follow-up.

  3. Overall Survival [ Time Frame: Two years ]
    OS was defined as the time from the date of enrollment until death by any cause. Participants still alive at the time of data analysis were censored at the date of last follow-up.

  4. Progression Free Survival [ Time Frame: Two years ]
    PFS was measured from the date of enrollment to the date of disease progression as defined by Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 or death due to any cause, whichever occurred first.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age at least 18 years.
  • ECOG PS 0-1.
  • Pathologically confirmed stage IV NSCLC.
  • Negative for driver genes including EGFR,ALK,and ROS-1.
  • Patients with disease progression after first-line platinum-based therapy without anti-PD-1 or PD-L1 treatment.
  • Patients with at least one lesion (size 1-5cm) eligible for SBRT (24Gy/3Fx) and simultaneously at least one measurable lesion (in addition to the lesion treated with SBRT) as defined by RECIST1.1.
  • Patients with brain metastasis are eligible if they are asymptomatic, neurologically stable, and off corticosteroids.
  • Life expectancy of more than 3 months.
  • Patients with no indications for palliative radiotherapy in the opinion of the investigator.
  • Patients with a prior history of surgery are eligible if they have recovered adequately from the toxicity and/or complications of surgery.
  • Signed informed consent for the use of fresh tumor biopsies before and during the treatment.
  • Women of childbearing age and men must agree to use effective contraception during the trial.
  • Adequate organ function within 1 week prior to the enrollment:

    1. Adequate bone marrow function: hemoglobin ≥80g/L, white blood cell (WBC) count ≥ 4.0 * 10 ^ 9/L or neutrophil count ≥ 1.5 * 10 ^ 9/L, and platelet count ≥ 100 * 10 ^ 9/L;
    2. Adequate hepatic function: total bilirubin < 1.5 x upper limit of normal (ULN). Note: If total bilirubin is > 1.5 x ULN, direct bilirubin must ≤ ULN, Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤2.5 ULN;
    3. Adequate renal function: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min;
  • Ability to understand and willingness to provide the informed consent.

Exclusion Criteria:

  • Prior exposure to immunomodulatory agent,including but limited to anti-PD-1 or anti-PD-L1 antibodies.
  • Severe autoimmune disease: inflammatory bowel disease (including Crohn's disease and ulcerative colitis) 、rheumatoid arthritis、scleroderma、systemic lupus erythematosus 、Wegener's granulomatosis and related vasculitides.
  • Patients receiving non-platinum-based chemotherapy as first-line treatment
  • Mixed small cell with non-small cell lung cancer histology.
  • Pregnant or lactating women.
  • Symptomatic interstitial lung disease or active infectious/non-infectious pneumonitis.
  • History of any other malignancy.
  • Patients in whom palliative radiotherapy is indicated in the opinion of the investigator.
  • Active infection, congestive heart failure, myocardial infarction within the 6 months prior to enrollment, unstable angina pectoris or cardiac arrhythmia.
  • Prior allergic reaction or contraindications to sintilimab and GM-CSF.
  • Patients who have received tumor vaccine; or administration of live, attenuated vaccine within 4 weeks before the start of treatment. Note: Influenza vaccination is permitted only during influenza season, while live, attenuated influenza vaccine such as FluMist is not allowed.
  • Patients receiving concurrent chemotherapy drugs,other immunosuppressive agents,or other investigational treatment.Long-term corticosteroid users are also excluded.
  • Mental disorders, drug abuse, and social condition that may negatively impact compliance in the opinion of the investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04106180

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Contact: Zhengfei Zhu, MD +86-18017312901
Contact: Jianjiao Ni, MD 13761974092

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Fudan University Shanghai Cancer Center Recruiting
Shanghai, China
Contact: Zhengfei Zhu, MD    +86-18017312901   
Contact: Jianjiao Ni, MD    13761974092   
Sponsors and Collaborators
Fudan University
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Principal Investigator: Zhengfei Zhu, MD Fudan University
Study Director: Xinghao Ai Shanghai Chest Hospital
Study Director: Zhengbo Han Shengjing Hospital
Study Director: Qian Chu Tongji Hospital
Study Director: Xiaorong Dong Union Hospital
Study Director: Lin Wu Hunan Cancer Hospital

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Responsible Party: Zhengfei Zhu, Professor, Fudan University Identifier: NCT04106180    
Other Study ID Numbers: Sword
First Posted: September 26, 2019    Key Record Dates
Last Update Posted: September 26, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Immunologic Factors
Physiological Effects of Drugs