Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
non small cell lung cancer, Sintilimab, Anlotinib, neoadjuvant therapy
Brief summary
This is a prospective single-center, open-label, phase II study evaluating the efficacy of sintilimab plus anlotinib as a neoadjuvant regimen in the treatment of IB-IIIB resectable non-small cell lung cancer.
Interventions
DRUGSintilimab
200mg, every 3 weeks, 3 cycles, in the neoadjuvant setting, and adjuvant 200mg,every 3 weeks no more than one year
DRUGAnlotinib
8mg, orally, D1-14, every 3 weeks, 2 cycles in only neoadjuvant setting
Sponsors
Ningbo No.2 Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Providing written informed consent prior to initiating the study. 2. Regardless of sex, aged ≥18 years and ≤75 years. 3. Histologically confirmed NSCLC. 4. At least one radiologically measureable lesion according to response evaluation criteria in solid tumors version 1.1(RECIST V1.1). 5. Treatment-naïve IB-IIIB resectable NSCLC (American Joint Committee on Cancer 8th tumor-node-metastasis classification). 6. Epidermal growth factor receptor(EFGR)/anaplastic lymphoma kinase(ALK)/ROS proto-oncogene 1(ROS1) wild type NSCLC. 7. Absence of bleeding risk. 8. Consent to surgical treatment. 9. Indication for surgery confirmed by surgeons. 10. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 11. Expected survival time more than 6 months. 12. Sufficient organ reserve, detailed as follows:(1) the absolute neutrophil count ≥1.5×109/L without the use of granulocyte colony-stimulating factor for the past 14 days prior to the first dose of study drugs;(2) platelet count ≥100×109/L without blood transfusion within the 2 weeks before the enrollment;(3) hemoglobin \>9g/dL without recent usage of blood transfusion 14 days prior to the study;(4) total bilirubin ≤ 1.5 fold the upper limit of normal (ULN), or total bilirubin \>1.5 fold ULN but direct bilirubin ≤ 1 fold ULN;(5) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN;(6) blood creatinine ≤ 1.5 fold ULN and creatinine clearance (calculated by the Cockcroft-Gault formula) ≥ 60ml/min;(7) adequate coagulation function, defined by international normalized ratio (INR) or prothrombin time(PT) less than 1.5 fold ULN;(8) normal thyroid function defined by the normal range of thyroid-stimulating hormone (TSH); otherwise, abnormal level of TSH with normal range of T3(or Ft3) and Ft4;(8) cardiac enzyme profile within the normal limits (merely laboratory abnormity without clinical significance based on investigator's decision is allowed) 13. For female participants of childbearing age, a urine or serum pregnancy test should be performed within 3 days before receiving the first dose of the study drugs, and the result must be negative. If the urine pregnancy test result is inconclusive, a blood pregnancy test is warranted. Postmenopausal women are defined as those who have been without menstruation for at least 1 year, or have undergone surgical sterilization or hysterectomy. 14. In the presence of pregnancy risk, all participants (both male and female) are required to use contraceptive measures with an annual failure rate of less than 1% throughout the entire treatment period up to 120 days following the last dose of the study drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| major pathological response (MPR) | 10 days postoperatively | Viable tumor cells are no more than 10% in the resected specimen |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| pathological complete response (pCR) | 10 days postoperatively | Viable tumor cells are not found in the resected specimen |
| treatment-related adverse events (TRAEs) | 90 days after the last dose of study drugs | TRAEs including immune-related adverse reaction are documented and graded based on the US National Cancer Institute's Common Terminology Criteria for Adverse Events 5.0 criteria. |
| rate of operative complications | 30 days postoperatively | The rate of surgical complications (such as bleeding, bronchopleural fistula,ect) are recorded and graded according to Clavien-Dindo criteria |
| overall survival(OS) | 5 years | OS is defined as the duration between the date of surgery and the date of all-cause death |
| disease-free survival (DFS) | 5 years | DFS is defined as the duration between the date of surgery and the date on which tumor recurrence is confirmed |
Other
| Measure | Time frame | Description |
|---|---|---|
| minimal residual disease (MRD) | 5 years | MRD is evaluated by testing circulating tumor DNA (ctDNA) in peripheral blood sample using next-generation sequencing(NGS) method. Each participant will undergo a minium of 3 tests for MRD. |
Contacts
Primary ContactFajiu Wang, PhD
Outcome results
None listed