Anlotinib, Gastric Cancer, Immunotherapy, Toripalimab
Conditions
Brief summary
This study is designed to evaluate the efficacy and safety of the combination of Anlotinib wiht Toripalimab in advanced gastric cancer with ECOG 2 as first-line regimen.
Detailed description
Anlotinib is a new, orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit. Toripalimab is a humanized immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed cell death 1 (programmed death-1; PD-1), with potential immune checkpoint inhibitory and antineoplastic activities. In the present study, we design a single-arm, single center Phase II trial to evaluate the efficacy and safety of the combination of Anlotinib wiht Toripalimab in advanced gastric cancer with ECOG 2 as first-line treatment.
Interventions
DRUGAnlotinib Plus Toripalimab
Anlotinib 12mg oral administration daily d1-d14, q3w; Toripalimab 240mg iv drop d1, q3w
Sponsors
Shanghai Changzheng Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed, UICC stage IV gastric cancer; * no prior systematic anti-cancer treatment and relapse or metastases was occurred more than 12 months after adjuvant chemotherapy; * at least one measurable lesion; * received radiotherapy 3 weeks before recruitment, but the lesion undergoing radiotherapy could not be used to calculate clinical benefit using RECISET criteria; * ECOG performance status 2; * the main organ function to meet the following criteria: HB ≥ 90g / L, ANC ≥ 1.5 × 109 / L, PLT ≥ 80 × 109 / L,BIL \<1.5 times the upper limit of normal (ULN), ALT and AST \<2.5 × ULN and if liver metastases, BIL \< 3 × ULN, ALT and AST \<5 × ULN; Serum Cr ≤ 1.5 × ULN; * Patient's written declaration of consent obtained; * Estimated life expectancy \> 3 months;
Exclusion criteria
* harboring HER2 positive including IHC 3+ or IHC 2+ with Fish positive; * dMMR/MSI-H; * Myocardial infarction, unstable angina pectoris, Grade III or IV heart failure (NYHA classification); * have received anlotinib or other immune checkpoint inhibitor ; * with known or clinically suspected brain metastases, autoimmune disease, organ transplantation ; * severe wounds or surgery 4 weeks before recruitment; * received glucocorticoid (more than 10mg prednisone ) and immunosuppressive agents; * History of a second malignancy during the past 5 years before inclusion in the study or during participation in the study, with the exception of a dermal basal cell or squamous cell carcinoma or cervical carcinoma in situ, if these were treated curatively. * pregnancy or breast feeding; * absent or restricted legal capacity; * a significant concomitant disease which, in the investigating physician's opinion, rules out the patient's participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| objective response rate | Evaluation of tumor burden based on RECIST criteria through study completion, an average of 8 weeks | Proportion of patients with reduction in tumor burden of a predefined amount, including complete remission and partial remission |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progress Free Survival | Evaluation of tumor burden based on RECIST criteria until first documented progress through study completion, an average of 8 weeks | Time from treatment beginning until disease progression |
| Overall Survival | From date of treatment beginning until the date of death from any cause, through study completion, an average of 8 weeks | Time from treatment beginning until death from any cause |
| Deepness of response | Evaluation of tumor burden based on RECIST criteria through study completion, an average of 8 weeks | Investigation of depth of response during first-line treatment |
| Disease control rate | Evaluation of tumor burden based on RECIST criteria through study completion, an average of 8 weeks | Proportion of patients with reduction and non-change in tumor burden of a predefined amount, including complete remission, partial remission and stable disease |
| adverse events | Through study completion, an average of 4 weeks | Incidence of Treatment-related adverse Events |
Countries
China
Outcome results
None listed