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

NCT04106180 | Unknown Phase 2

• 1 other identifier: Sword
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

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.

Conditions

NSCLC Stage IV

Outcome Measures

Primary Outcomes (1)

• Overall Objective Response Rate

  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.

  At least 6 weeks after start of treatment

Secondary Outcomes (4)

• Percentage of Participants With Adverse Events

  Two years

• Objective Response Rate (ORR) in Non-irradiated Lesion

  At least 6 weeks after start of treatment

• Overall Survival

  Two years

• Progression Free Survival

  Two years

Study Arms (1)

SBRT + sintilimab + GM-CSF

EXPERIMENTAL

Drug: GM-CSF; Drug: Sintilimab; Radiation: SBRT

Interventions

GM-CSF DRUG

Patients will receive GM-CSF 125μg/m2 daily for 14 consecutive days after completing SBRT treatment.

SBRT + sintilimab + GM-CSF

Sintilimab DRUG

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

SBRT + sintilimab + GM-CSF

SBRT RADIATION

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.

Also known as: Stereotactic body radiation therapy

SBRT + sintilimab + GM-CSF

Eligibility Criteria

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

You may qualify if:

• 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：
• 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;
• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, China

RECRUITING

Related Publications (1)

• 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.

  PMID: 34526044 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor; sintilimab; Radiosurgery

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)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Zhengfei Zhu, MD

  Fudan University

  PRINCIPAL INVESTIGATOR

• 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

  STUDY DIRECTOR

Central Study Contacts

Zhengfei Zhu, MD

CONTACT

+86-18017312901; fuscczzf@163.com

Jianjiao Ni, MD

CONTACT

13761974092; nijianjiao8@sina.com

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

Study Record Dates

• First Submitted: September 24, 2019
• First Posted: September 26, 2019
• Study Start: September 30, 2019
• Primary Completion: August 31, 2022
• Study Completion: August 31, 2023
• Last Updated: September 26, 2019

Record last verified: 2019-09

Locations

CN (1)