Conversion Therapy of Sintilimab in Combination With Apatinib and Chemotherapy in Stage IV Gastric Cancer

Gastric Cancer Stage IV Clinical Trial

Official title:

Efficacy and Safety of Conversion Therapy With Sintilimab in Combination With Chemotherapy and Apatinib in Patients With Stage IV Gastric Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04267549
• Other study ID #: E20207
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 1, 2019
• Est. completion date: August 30, 2023

Study information

• Verified date: May 2023
• Source: Tianjin Medical University Cancer Institute and Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 47
• Est. completion date: August 30, 2023
• Est. primary completion date: December 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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;

Related Conditions & MeSH terms

• Gastric Cancer Stage IV
• Stomach Neoplasms

Intervention

Drug:
• sintilimab
a checkpoint inhibitor via blocking PD-1 (programmed cell death-1) site of signaling.
• apatinib
a multi-target anti-angiogenic tyrosine kinase inhibitor (TKI)
• S1
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).
• Nab paclitaxel
Nab paclitaxel is a albumin-bound well tolerated paclitaxel than traditional paclitaxel

Locations

Country	Name	City	State
China	Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Tianjin Medical University Cancer Institute and Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	pathological response	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.	up to one year after surgery
Primary	R0-surgery conversion rate	The proportion of participants who underwent R0 surgery among all participants.	up to one year
Secondary	objective response rate (ORR)	The proportion of participants who achieved complete response(CR) or partial response(PR) per Response Evaluation Criteria in Solid Tumors criteria (RECIST v1.1).	up to one year
Secondary	disease control rate (DCR)	The proportion of participants who achieved CR, PR or stable disease(SD) per RECIST v1.1.	up to one year
Secondary	conversion rate	The proportion of participants who underwent surgery among all participants.	up to one year
Secondary	overall survival (OS)	The time from the first dose of the study treatment to death from any cause.	up to two years
Secondary	event-free survival (EFS)	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.	up to two years
Secondary	Treatment-Related Adverse Events (TRAEs)	The grade and proportion of participants who experienced TRAEs per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03	from the first day of treatment until 1 month after the end of treatment
Secondary	surgery-related complications	Incidence and grade of surgery-related complications as assessed byper the Clavien-Dindo classification	from the day of surgery to 30 days postoperatively