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

Phase 2

Active, not recruiting

• Conditions: Gastric Cancer Stage IV
• Interventions: Drug: sintilimab; Drug: apatinib; Drug: S1; Drug: Nab paclitaxel

• Registration Number: NCT04267549
• Lead Sponsor: Tianjin Medical University Cancer Institute and Hospital

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-05-01
• Study First Submitted: 2020-01-21
• Study First Submitted QC: 2020-02-11
• Study First Posted: 2020-02-13
• Primary Completion: 2022-12-01
• Status Verified: 2023-05
• Last Update Submitted: 2023-07-03
• Last Update Posted: 2023-07-06
• Study Completion: 2023-08-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 47

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;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
treatment	Nab paclitaxel	Eligible patients will be given sintilimab(200mg iv, day 1), apatinib(250mg,once daily), S-1 (60mg, twice daily, day1-14) and nab-paclitaxel(without peritoneal metastases: 260 mg/m\^2 iv for 3h; with peritoneal metastases: 200mg/m\^2 iv plus 60mg/m\^2 ip; day 1) every 3 weeks for at least 3 cycles. The feasibility of surgery will be evaluated by a multidisciplinary team every 2-4 cycles. Patients assessed as inoperable will be allowed to continue maintenance therapy with the original regimen until disease progression or intolerable toxicity. For patients assessed as operable, apatinib will be discontinued and one more cycle of sintilimab combined with S-1 and nab-paclitaxel will be administered; radical surgery will be performed within 2-4 weeks after the end of treatment. Safety run-in stage will be set in the first 6 patients to determine the safety. The study will be terminated if dose-limiting toxicities (DLTs) occur in more than 2 patients.
treatment	S1	Eligible patients will be given sintilimab(200mg iv, day 1), apatinib(250mg,once daily), S-1 (60mg, twice daily, day1-14) and nab-paclitaxel(without peritoneal metastases: 260 mg/m\^2 iv for 3h; with peritoneal metastases: 200mg/m\^2 iv plus 60mg/m\^2 ip; day 1) every 3 weeks for at least 3 cycles. The feasibility of surgery will be evaluated by a multidisciplinary team every 2-4 cycles. Patients assessed as inoperable will be allowed to continue maintenance therapy with the original regimen until disease progression or intolerable toxicity. For patients assessed as operable, apatinib will be discontinued and one more cycle of sintilimab combined with S-1 and nab-paclitaxel will be administered; radical surgery will be performed within 2-4 weeks after the end of treatment. Safety run-in stage will be set in the first 6 patients to determine the safety. The study will be terminated if dose-limiting toxicities (DLTs) occur in more than 2 patients.
treatment	sintilimab	Eligible patients will be given sintilimab(200mg iv, day 1), apatinib(250mg,once daily), S-1 (60mg, twice daily, day1-14) and nab-paclitaxel(without peritoneal metastases: 260 mg/m\^2 iv for 3h; with peritoneal metastases: 200mg/m\^2 iv plus 60mg/m\^2 ip; day 1) every 3 weeks for at least 3 cycles. The feasibility of surgery will be evaluated by a multidisciplinary team every 2-4 cycles. Patients assessed as inoperable will be allowed to continue maintenance therapy with the original regimen until disease progression or intolerable toxicity. For patients assessed as operable, apatinib will be discontinued and one more cycle of sintilimab combined with S-1 and nab-paclitaxel will be administered; radical surgery will be performed within 2-4 weeks after the end of treatment. Safety run-in stage will be set in the first 6 patients to determine the safety. The study will be terminated if dose-limiting toxicities (DLTs) occur in more than 2 patients.
treatment	apatinib	Eligible patients will be given sintilimab(200mg iv, day 1), apatinib(250mg,once daily), S-1 (60mg, twice daily, day1-14) and nab-paclitaxel(without peritoneal metastases: 260 mg/m\^2 iv for 3h; with peritoneal metastases: 200mg/m\^2 iv plus 60mg/m\^2 ip; day 1) every 3 weeks for at least 3 cycles. The feasibility of surgery will be evaluated by a multidisciplinary team every 2-4 cycles. Patients assessed as inoperable will be allowed to continue maintenance therapy with the original regimen until disease progression or intolerable toxicity. For patients assessed as operable, apatinib will be discontinued and one more cycle of sintilimab combined with S-1 and nab-paclitaxel will be administered; radical surgery will be performed within 2-4 weeks after the end of treatment. Safety run-in stage will be set in the first 6 patients to determine the safety. The study will be terminated if dose-limiting toxicities (DLTs) occur in more than 2 patients.

Primary Outcome Measures

Name	Time	Method
R0-surgery conversion rate	up to one year	The proportion of participants who underwent R0 surgery among all participants.

Secondary Outcome Measures

Name	Time	Method
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).
overall survival (OS)	up to two years	The time from the first dose of the study treatment to death from any cause.
disease control rate (DCR)	up to one year	The proportion of participants who achieved CR, PR or stable disease(SD) per RECIST v1.1.
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.
conversion rate	up to one year	The proportion of participants who underwent surgery among all participants.
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

Trial Locations

Locations (1)

Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital; 🇨🇳 Tianjin, Tianjin, China