Clinical trial NCT04106180: SBRT in Combination With Sintilimab and GM-CSF for the Treatment of Advanced NSCLC
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: NSCLC Stage IV
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2019-09-26
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall Objective Response Rate
timeFrame: At least 6 weeks after start of treatment
Secondary outcomes:
measure: Percentage of Participants With Adverse Events
timeFrame: Two years
measure: Objective Response Rate (ORR) in Non-irradiated Lesion
timeFrame: At least 6 weeks after start of treatment
measure: Overall Survival
timeFrame: Two years
measure: Progression Free Survival
timeFrame: Two years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
Study officials:
affiliation: Fudan University
name: Zhengfei Zhu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Shanghai Chest Hospital
name: Xinghao Ai
role: STUDY_DIRECTOR
affiliation: Shengjing Hospital
name: Zhengbo Han
role: STUDY_DIRECTOR
affiliation: Tongji Hospital
name: Qian Chu
role: STUDY_DIRECTOR
affiliation: Union Hospital
name: Xiaorong Dong
role: STUDY_DIRECTOR
affiliation: Hunan Cancer Hospital
name: Lin Wu
role: STUDY_DIRECTOR
References:
citation: Ni J, Zhou Y, Wu L, Ai X, Dong X, Chu Q, Han C, Wang X, Zhu Z. Sintilimab, stereotactic body radiotherapy and granulocyte-macrophage colony stimulating factor as second-line therapy for advanced non-small cell lung cancer: safety run-in results of a multicenter, single-arm, phase II trial. Radiat Oncol. 2021 Sep 15;16(1):177. doi: 10.1186/s13014-021-01905-3.