Anlotinib Plus Toripalimab as First-line Treatment for Advanced Gastric or Gastro-esophageal Junction Cancer (APICAL-GE)

Study Overview
=================
Brief Summary
-----------------
This study is designed to evaluate the efficacy and safety of the combination of Anlotinib wiht Toripalimab in advanced gastric or gastro-oesophageal junction cancer as first-line treatment.

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 or gastro-oesophageal junction cancer as first-line treatment.

Official Title
-----------------
Anlotinib Plus Toripalimab as First-line Treatment for Patients With Advanced Gastric or Gastro-esophageal Junction Cancer (APICAL-GE): a Single Center, Single-arm Phase II Study

Conditions
-----------------
Gastric Cancer, Gastro-oesophageal Junction Cancer, Immunotherapy, Anlotinib, Toripalimab

Intervention / Treatment
-----------------
* Drug: Anlotinib Plus Toripalimab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed, UICC stage IV gastric or gastro-oesophageal junction 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 0-1; 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anlotinib Plus Toripalimab<br>the combination of Anlotinib Plus Toripalimab as first-line treatment | Drug: Anlotinib Plus Toripalimab<br>* Anlotinib 12mg oral administration daily d1-d14, q3w; Toripalimab 240mg iv drop d1, q3w<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate | Proportion of patients with reduction in tumor burden of a predefined amount, including complete remission and partial remission | Evaluation of tumor burden based on RECIST criteria through study completion, an average of 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress Free Survival | Time from treatment beginning until disease progression | Evaluation of tumor burden based on RECIST criteria until first documented progress through study completion, an average of 8 weeks | 
| Overall Survival | Time from treatment beginning until death from any cause | From date of treatment beginning until the date of death from any cause, through study completion, an average of 8 weeks | 
| Deepness of response | Investigation of depth of response during first-line treatment | Evaluation of tumor burden based on RECIST criteria through study completion, an average of 8 weeks | 
| Disease control rate | Proportion of patients with reduction and non-change in tumor burden of a predefined amount, including complete remission, partial remission and stable disease | Evaluation of tumor burden based on RECIST criteria through study completion, an average of 8 weeks | 
| adverse events | Incidence of Treatment-related adverse Events | Through study completion, an average of 4 weeks |