Gastric Cancer Stage IV
Conditions
Keywords
PD-1 inhibitor, conversion therapy
Brief summary
This is a single-arm, phase II study aiming to evaluate the feasibility and efficacy of sintilimab (PD-1 inhibitor) in combination of apatinib and two-drug chemotherapy (S-1 plus nab-paclitaxel) as conversion therapy in patients with stage IV gastric cancer in China.
Interventions
DRUGsintilimab
a checkpoint inhibitor via blocking PD-1 (programmed cell death-1) site of signaling.
DRUGapatinib
a multi-target anti-angiogenic tyrosine kinase inhibitor (TKI)
DRUGS1
S-1 is an oral fluoropyrimidine consisting of tegafur (a prodrug that is converted to fluorouracil, mainly in liver microsomes but also in tumour tissue), gimeracil (an inhibitor of dihydropyrimidine dehydrogenase, which degrades 5-FU), and oteracil (which inhibits the phosphorylation of 5-FU in the gastrointestinal tract, thereby reducing the toxic effects of 5-FU in the intestinum).
DRUGNab paclitaxel
Nab paclitaxel is a albumin-bound well tolerated paclitaxel than traditional paclitaxel
Sponsors
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
eligible patients will be given treatment of sintilimab, apatinib and chemotherapy (nab-paclitaxel) every 3 weeks
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* gastric adenocarcinoma confirmed by gastroscopy and pathology (histologically/cytologically ) ; * life expectancy of ≥3-month； * unresectable patients who were initially diagnosed as stage IV (clinical stage, American Joint Committee on Cancer 8th edition); * Eastern Cooperative Oncology Group performance status: 0-1; * must have at least 1 of the following unresectable factors indicated by CT, MRI or positron emission tomography(PET)-CT: 1. N3 lymphatic metastasis; 2. Extensive or bulky lymph nodes; 3. T4b; 4. Hepatic metastasis: ≤5 lesions, total diameter of ≤8cm; 5. Peritoneal metastasis (CY1, P1); 6. Kukernburg tumor; * adequate organ function; * pregnant test negative of females of childbearing potential , and willing to use adequate contraception; * written Informed Consensus Form;
Exclusion criteria
* prior use of any checkpoint inhibitor treatment, including PD-1, programmed cell death ligand-1(PDL-1), CTLA4 etc; * Her-2 positive with willing to use herceptin treatment; * prior active autoimmune disease or history of autoimmune disease; * clinically significant cardiovascular and cerebrovascular diseases, including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, or coronary artery bypass surgery, Congestive heart failure (New York heart association (NYHA) class \> 2), ventricular arrhythmia which need medical intervention, left ventricular ejection fraction(LVEF) \< 50%; * not controlled hypertension; * prior systemic treatment to metastatic disease； * previous digestive tract bleeding history within 3 months or evident gastrointestinal bleeding tendency; * history of immunodeficiency including seropositivity for human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease, or active hepatitis ; * patients who may receive vaccination during study period; * mental disorders history, or psychotropic drug abuse history; * unable to orally administration;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| R0-surgery conversion rate | up to one year | The proportion of participants who underwent R0 surgery among all participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| objective response rate (ORR) | up to one year | The proportion of participants who achieved complete response(CR) or partial response(PR) per Response Evaluation Criteria in Solid Tumors criteria (RECIST v1.1). |
| disease control rate (DCR) | up to one year | The proportion of participants who achieved CR, PR or stable disease(SD) per RECIST v1.1. |
| conversion rate | up to one year | The proportion of participants who underwent surgery among all participants. |
| event-free survival (EFS) | up to two years | The time from the first dose of the study treatment to any of the following events: progression of disease, local or distant recurrence, or death due to any cause. |
| Treatment-Related Adverse Events (TRAEs) | from the first day of treatment until 1 month after the end of treatment | The grade and proportion of participants who experienced TRAEs per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 |
| surgery-related complications | from the day of surgery to 30 days postoperatively | Incidence and grade of surgery-related complications as assessed byper the Clavien-Dindo classification |
| overall survival (OS) | up to two years | The time from the first dose of the study treatment to death from any cause. |
Other
| Measure | Time frame | Description |
|---|---|---|
| pathological response | up to one year after surgery | Pathological response of the primary tumor was graded according to tumor regression grade (TRG) as follows: 0. (CR), no viable cancer cells, including lymph nodes; 1. (near CR), single cells or rare small groups of cancer cells; 2. (PR), residual cancer cells with evident tumor regression but more than single cells or rare small groups of cancer cells; and 3. (poor or no response), extensive residual cancer with no evident tumor regression. |
Countries
China
Outcome results
None listed