Clinical trial NCT04278222: Anlotinib Plus Toripalimab as First-line Treatment for Advanced Gastric Cancer With ECOG 2 (APICAL-GC)
Official title: Efficacy and Safety of Anlotinib Plus Toripalimab as First-line Regimen in Frail Patients (ECOG 2) With Advanced Gastric Cancer (APICAL-GC): an Open-label, Single Arm, Phase II Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Gastric Cancer
Immunotherapy
Anlotinib
Toripalimab
Lead sponsor: Shanghai Changzheng Hospital
Sponsor class: OTHER
First posted: 2020-02-20
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: objective response rate
timeFrame: Evaluation of tumor burden based on RECIST criteria through study completion, an average of 8 weeks
Secondary outcomes:
measure: Progress Free Survival
timeFrame: Evaluation of tumor burden based on RECIST criteria until first documented progress through study completion, an average of 8 weeks
measure: Overall Survival
timeFrame: From date of treatment beginning until the date of death from any cause, through study completion, an average of 8 weeks
measure: Deepness of response
timeFrame: Evaluation of tumor burden based on RECIST criteria through study completion, an average of 8 weeks
measure: Disease control rate
timeFrame: Evaluation of tumor burden based on RECIST criteria through study completion, an average of 8 weeks
measure: adverse events
timeFrame: Through study completion, an average of 4 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of Medical Oncology, Shanghai Changzheng Hospital
Study officials:
References:
citation: Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore). 2022 May 27;101(21):e29304. doi: 10.1097/MD.0000000000029304.