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

Tianjin Medical University

Status and phase: Active, not recruiting; Phase 2

Conditions: Gastric Cancer Stage IV

Treatments: Drug: sintilimab; Drug: Nab paclitaxel; Drug: apatinib; Drug: S1

Study type: Interventional

Funder types: Other

Identifiers

NCT04267549

E20207

Details and patient eligibility

About

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.

Enrollment: 47 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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;

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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47 participants in 1 patient group

treatment

Experimental group

Description:

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:

Drug: Nab paclitaxel

Drug: apatinib

Drug: sintilimab

Drug: S1