A Phase II, Prospective, Single-center, Randomized, Controlled Study to Investigate the Efficacy and Safety of Sintilimab or Placebo in Combination With Chemotherapy as Second-line Treatment for Patients With Stage IV Nonsquamous Non-small Cell Lung Cancer With Wild-type EGFR After Failure With Platinum-Containing Chemotherapy
Overview
- Phase
- Phase 2
- Intervention
- Sintilimab
- Conditions
- Nonsquamous Non-Small Cell Lung Cancer
- Sponsor
- Xin-Hua Xu
- Enrollment
- 70
- Locations
- 1
- Primary Endpoint
- Compare Overall Survival (OS) between sintilimab +chemotherapy and placebo + chemotherapy.
- Last Updated
- 4 years ago
Overview
Brief Summary
This prospective, single-center, randomized, controlled study will evaluate the efficacy and safety of sintilimab or placebo in combination with chemotherapy as second-line treatment for patients with stage IV nonsquamous non-small cell lung cancer with wild-type EGFR after failure with platinum-containing chemotherapy. Treatment may continue as long as participants are experiencing clinical benefit as assessed by the investigator, i.e., in the absence of unacceptable toxicity or symptomatic deterioration attributed to disease progression.
Investigators
Xin-Hua Xu
professor
China Three Gorges University, Yichang, China
Eligibility Criteria
Inclusion Criteria
- •Volunteer to participate in clinical research; fully understand and know the research and sign informed consent;
- •Age ≥ 18 years old and ≤ 75 years old, either sex;
- •Eastern Collaborative Oncology Group Performance status (ECOG PS) 0, 1 or 2;
- •Has a histologically or cytologically confirmed diagnosis of stage IV (according to the 8th edition of the International Association for the Study of Lung Cancer) nonsquamous NSCLC;
- •Have at least one measurable lesion as defined by RECIST 1.1;
- •Has progression of disease after treatment with at least two cycles of a platinum-containing doublet chemotherapy according to RECIST V.1.1;
- •Patients without activating EGFR mutation;
- •Normal hepatic function: total bilirubin≤1.5×normal upper limit (ULN); Alanine aminotransferase and Aspartate aminotransferase levels ≤2.5×ULN or ≤5×ULN if liver metastasis is present;
- •Normal renal function: Creatinine ≤1.5×ULN or calculated creatinine clearance ≥45 mL/min (using Cockcroft/Gault formula to calculate );
- •Normal hematological function: absolute neutrophil count ≥1.5×109/L, platelet count ≥70×109/L, hemoglobin≥80g/L \[no blood transfusion or erythropoietin (EPO) within 7 days\] Dependency\];
Exclusion Criteria
- •ECOG PS \>2;
- •Small cell lung cancer and squamous NSCLC;
- •EGFR mutation or mutation status unknown;
- •Known hypersensitivity or allergy to monoclonal antibody;
- •Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2, anti-tumor necrosis factor CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways);
- •Active autoimmune disease, or a documented history of autoimmune disease;
- •Treatment with systemic corticosteroids (prednisone≥10mg per day or equivalent dose) or other systemic immunosuppressive medications within 2 weeks prior to the first dose;
- •Known history or active human immunodeficiency virus (HIV);
- •Known acute or chronic active hepatitis B (HBV DNA positive) infection or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA positive) infection;
- •Interstitial lung disease, or history of pneumonitis requiring systemic steroids for treatment;
Arms & Interventions
Sintilimab plus chemotherapy
Sintilimab (200 mg) plus chemotherapy (physicians' choice between docetaxel and pemetrexed) every 3 weeks.
Intervention: Sintilimab
Sintilimab plus chemotherapy
Sintilimab (200 mg) plus chemotherapy (physicians' choice between docetaxel and pemetrexed) every 3 weeks.
Intervention: Docetaxel
Sintilimab plus chemotherapy
Sintilimab (200 mg) plus chemotherapy (physicians' choice between docetaxel and pemetrexed) every 3 weeks.
Intervention: Pemetrexed
Placebo plus chemotherapy
Placebo plus chemotherapy (physicians' choice between docetaxel and pemetrexed) every 3 weeks.
Intervention: Docetaxel
Placebo plus chemotherapy
Placebo plus chemotherapy (physicians' choice between docetaxel and pemetrexed) every 3 weeks.
Intervention: Pemetrexed
Placebo plus chemotherapy
Placebo plus chemotherapy (physicians' choice between docetaxel and pemetrexed) every 3 weeks.
Intervention: Placebo
Outcomes
Primary Outcomes
Compare Overall Survival (OS) between sintilimab +chemotherapy and placebo + chemotherapy.
Time Frame: approximately 24 months
To compare the efficacy of the combination of sintilimab and chemotherapy versus placebo and chemotherapy in terms of overall survival (OS) in patients with stage IV nonsquamous non-small cell lung cancer with wild-type EGFR after failure with platinum-containing chemotherapy. Overall Survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as dead at the time of analysis was censored at the date when they were last known to be alive.
Secondary Outcomes
- Compare duration of response between sintilimab +chemotherapy and placebo + chemotherapy.(approximately 24 months)
- Compare objective response rate between sintilimab +chemotherapy and placebo + chemotherapy.(approximately 24 months)
- Compare Progression Free Survival (PFS) between sintilimab +chemotherapy and placebo + chemotherapy using RECIST 1.1.(approximately 24 months)
- Number of Participants who Experience Treatment Related Adverse Events (AEs).(approximately 24 months)