A Single-center Phase 2 Study of Neoadjuvant Immunotherapy Plus Chemotherapy for Potentially Resectable Stage IIIA/IIIB Non-Small Cell Lung Cancer
Overview
- Phase
- Phase 2
- Intervention
- Sintilimab Injection
- Conditions
- IIIA Stage Non-small Cell Lung Cancer
- Sponsor
- The First Hospital of Jilin University
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- 2 years DFS rate
- Status
- Active, not recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
Cancer has always been one of the leading causes of death in the world, and China is facing more and more severe challenges from cancer. Among all the causes of cancer death, lung cancer (25.2%) ranks first, among which non-small cell lung cancer (NSCLC) accounts for about 80% to 85%, of which about 1 / 3 of the patients have been in the local advanced stage (IIIA stage / IIIB stage) at the time of initial diagnosis. For the patients with stage IIIA NSCLC who can be operated on, surgery is still the most effective way to treat them. Even so, NSCLC in stage I-III undergoing radical surgery is the most effective way 30-60% of the patients eventually had relapse or distant metastasis. Therefore, people began to explore a new treatment mode, preoperative neoadjuvant chemotherapy, to improve the survival rate of NSCLC 2.
At present, the NCCN guidelines for the new adjuvant treatment of NSCLC mainly recommend platinum based dual drug chemotherapy.
Immunotherapy combined with chemotherapy will be a potential new adjuvant therapy in the future, which can improve the resection rate of patients, reduce the recurrence rate after surgery, and have tolerable adverse reactions.
Detailed Description
Sample size calculation： The primary endpoint is the 2-year DFS rate，however, due to the extended observation time required for this endpoint, it is not suitable for promptly validating treatment response. MPR rate is employed to calculate the necessary sample size. Simon's optimal two-stage design is utilized. The addition of sintilimab to chemotherapy is assumed to elevate the MPR rate from 8.9% to 35%. The sample size should be 29(17+12). In the first stage, the study will be concluded if ≤2 patients achieve MPR, indicating a negative outcome. Conversely, if more than 4 patients achieve MPR, the study will proceed by enrolling an additional 12 patients. Considering the sample size calculation results and sufficient funding, the final enrollment is 30. The type 1 error rate is 0.05. The outlined protocol yield an 95% statistical power to detect an MPR rate of 35% under alternative hypotheses. MRD detectition： Using previously retained biomarkers from patients for MRD detection, exploring the relationship between MRD and patient DFS and OS.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Asian male or female patients: 18-75 years old;
- •ECoG physical condition score: 0-2;
- •Histologic examination confirmed that the potential resectable stage IIIA/IIIB non-small cell lung cancer (T4 or N2 according to the TNM staging standard of AJCC 8th Edition);
- •Estimated survival time ≥ 12 weeks;
- •No systemic anti-tumor therapy has been received before. The function of main organs is normal, that is to say, the relevant examination indexes within 14 days before randomization meet the following requirements:
- •Blood routine examination:
- •a) Hemoglobin ≥ 90 g / L (no blood transfusion within 14 days); b) Neutrophil count ≥ 1.5 × 109 / L; c) Platelet count ≥ 100 × 109 / L;
- •Biochemical examination:
- •a) Total bilirubin ≤ 1.5 × ULN (upper limit of normal value); b) ALT or AST ≤ 2.5 × ULN; ALT or AST ≤ 5 × ULN in case of liver metastasis; c) Serum creatinine \< 1.5 times of the upper limit of normal value; endogenous creatinine clearance ≥ 50 ml / min (Cockcroft Gault formula);
- •Routine coagulation examination:
Exclusion Criteria
- •There are mixed small cell carcinoma and sarcoma in histology;
- •Other malignant tumors were diagnosed within 5 years before administration, excluding radical skin basal cell carcinoma, skin squamous cell carcinoma and / or radical resection of carcinoma in situ. If more than 5 years before the administration of the drug is diagnosed as other malignant tumors or lung cancer, it is necessary to carry out pathological or cytological diagnosis of the recurrent lesions;
- •Currently participating in the intervention clinical research and treatment, or receiving other drugs or research instruments within 4 weeks before the first administration;
- •Previously received the following therapies: anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or drugs for another stimulation or synergistic inhibition of T cell receptor (such as CTLA-4, OX-40, CD137);
- •Received immunomodulatory drugs (thymosin, interferon, interleukin, etc.) within 2 weeks before the first administration, or received major surgical treatment within 3 weeks before the first administration;
- •With a history of haemorrhagic disease, any bleeding event with a severe grade of 3 or more in ctcae5.0 occurred within 4 weeks before screening;
- •Received solid organ or blood system transplantation;
- •There are clinically uncontrolled active infections, including but not limited to acute pneumonia;
- •There were idiopathic pulmonary fibrosis, organic pneumonia (such as bronchiolitis obliterans), and drug-related pneumonia;
- •Uncontrollable or symptomatic hypercalcemia;
Arms & Interventions
experimental arm
Sintilimab+Albumin paclitaxel:+Carboplatin:
Intervention: Sintilimab Injection
Outcomes
Primary Outcomes
2 years DFS rate
Time Frame: 2 years
To evaluate the 2-year DFS rate of neoadjuvant treatment of Asian patients with resectable stage IIIA NSCLC with Sintilimab combined with albumin paclitaxel and carboplatin
Secondary Outcomes
- Downgrade rate(36 month)
- MPR rate(36 month)
- OS(36 month)
- PCR rate(36 month)
- DFS(36 month)
- TRAE(36 month)
- ORR(36 month)