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

NCT04267549 | Unknown Phase 2

• 1 other identifier: E20207
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastric Cancer Stage IV

Keywords

PD-1 inhibitor; conversion therapy

Outcome Measures

Primary Outcomes (1)

• R0-surgery conversion rate

  The proportion of participants who underwent R0 surgery among all participants.

  up to one year

Secondary Outcomes (7)

• objective response rate (ORR)

  up to one year

• disease control rate (DCR)

  up to one year

• conversion rate

  up to one year

• overall survival (OS)

  up to two years

• event-free survival (EFS)

  up to two years

Other Outcomes (1)

• pathological response

  up to one year after surgery

Study Arms (1)

treatment

EXPERIMENTAL

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.

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

Interventions

sintilimab DRUG

a checkpoint inhibitor via blocking PD-1 (programmed cell death-1) site of signaling.

Also known as: Tyvyt

treatment

apatinib DRUG

a multi-target anti-angiogenic tyrosine kinase inhibitor (TKI)

treatment

S1 DRUG

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).

treatment

Nab paclitaxel DRUG

Nab paclitaxel is a albumin-bound well tolerated paclitaxel than traditional paclitaxel

treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• N3 lymphatic metastasis;
• Extensive or bulky lymph nodes;
• T4b;
• Hepatic metastasis: ≤5 lesions, total diameter of ≤8cm;
• Peritoneal metastasis (CY1, P1);
• Kukernburg tumor;
• adequate organ function;
• pregnant test negative of females of childbearing potential , and willing to use adequate contraception;
• written Informed Consensus Form;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, 300060, China

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

sintilimab; apatinib; S 1 (combination); Taxes

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: eligible patients will be given treatment of sintilimab, apatinib and chemotherapy (nab-paclitaxel) every 3 weeks

Study Record Dates

• First Submitted: January 21, 2020
• First Posted: February 13, 2020
• Study Start: May 1, 2019
• Primary Completion: December 1, 2022
• Study Completion: August 30, 2023
• Last Updated: July 6, 2023

Record last verified: 2023-05

Locations

CN (1)