Camrelizumab Combined With Apatinib Mesylate Tablets, Nab-paclitaxel and S-1 in the Treatment of Locally Advanced Gastric Cancer

Camrelizumab Combined With Apatinib Mesylate Tablets, Nab-paclitaxel and S-1 in the Treatment of Locally Advanced Gastric Cancer: an Multicenter, Open, Randomized, Controlled Clinical Study

To evaluate the clinical efficacy and safety of camrelizumab combined with apatinib mesylate, nab-paclitaxel and S-1

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Gastric Cancer
• Intervention / Treatment: Drug: Camrelizumab; Drug: Apatinib Mesylate; Drug: nab-paclitaxel; Drug: S1

• Study Type: Interventional
• Enrollment (Estimated): 53
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350000
      • Fujian Medical University Union Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age: 18-75 years of age
• Gastric adenocarcinoma was confirmed by pathology（ including histology or cytology）。
• CT/MRI,PET-CT or laparoscopic exploration were used to confirm the diagnosis of gastric cancer staging as cT2-4a and/or N+ and M0 before operation.
• measurable lesions at least should be detected by CT/MRI examination in accordance with the RECIST1.1.（CT scan of tumor lesion length≥10mm，CT scan short diameter≥15mm，scan slice thicknes 5mm）
• ECOG（Eastern Cooperative Oncology Group）PS（Performance Status）:0-1 scores;
• the expected survival time is more than 12 weeks

• the main organ function is normal, which should meet the following criteria:

  (1) blood routine examination standards should be met（no blood transfusion within 14 days）

  a．HB≥ 100g/L b. WBC≥3×109/L c. ANC≥1.5×109/L d. PLT≥100×109/L （2）biochemical examination shall comply with the following criteria：

  1. BIL<1.5 normal upper limit ULN
  2. ALT and AST<2.5 ULN,GPT≤1.5×ULN
  3. Cr≤1 ULN，CCR（creatinine clearance rate）>60ml/min(Cockcroft-Gault formula)
• women of childbearing age must have a pregnancy test in 7 days before entering the group (in serum), and the results were negative, and willing to use appropriate contraception during the study period and the last 8 weeks after giving drug test; men should have the surgical sterilization, or adopt the appropriate contraceptive methods during the test and the last 8 weeks after giving drug test。
• No other clinical studies were conducted before and during the treatment
• participants is willing to participate in this study, sign the informed consent, have good compliance, cooperate with follow-up.

Exclusion Criteria:

• Previous history of chemotherapy, radiotherapy, targeted drug therapy or immunotherapy
• Patients with contraindications for surgical treatment and chemotherapy or whose physical condition and organ function do not allow for larger abdominal surgery
• patients with metastasis
• Having any active autoimmune diseases or a history of autoimmune diseases (such as interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); Patients with vitiligo or cured childhood asthma/allergies who did not need any intervention in adulthood were excluded; Autoimmune hypothyroidism treated with a stable dose of thyroid replacement hormone; Type 1 diabetes with stable doses of insulin
• A history of immunodeficiency, including HIV testing positive, or other acquired or congenital immunodeficiency disorders, or a history of organ transplantation and allogeneic bone marrow transplantation
• Accompanied by serious heart, lung, liver, kidney disease; Have nerve, mental disease; Jaundice or obstruction of the digestive tract with severe infection
• pregnant or lactating women
• The blood pressure of patients with hypertension cannot be reduced to the normal range by the antihypertensive drugs (systolic pressure >140 mmHg, diastolic pressure >90 mmHg)
• With Ⅰ magnitude of coronary heart disease, arrhythmia (including QTc protracted between male > 450 ms, women > 470 ms) and cardiac insufficiency
• Patients have a clear tendency with gastrointestinal bleeding, including the following situation: local active ulcerative lesions, and fecal occult blood (+ +); with melena and hematemesis history in 2 months; and patients with fecal occult blood (+) and unresected gastric primary tumor; patients with the risk of bleeding should take the gastroscopy test, if it is the gastric cancer, and researchers believe that may results in massive digestive tract hemorrhage；coagulation dysfunction (INR(international normalized ratio)>1.5, APTT(activated partial thromboplastin time)>1.5 ULN), with bleeding tendency;
• Subjects have failed to control good cardiovascular clinical symptoms or disease, including but not limited to: such as: (1) the NYHA class II heart failure (2) above unstable angina pectoris (3) occurred within 1 year (4) have clinical significance of myocardial infarction (mi) room sex or ventricular arrhythmias without clinical intervention on or after clinical intervention is still poorly controlled
• History of interstitial lung disease (except radiation pneumonia without hormone therapy), and history of non-infectious pneumonia
• Patients are positive of urine protein (urine protein detection 2+ or above, or 24 hours urine protein quantitative >1.0g);
• A person who has previously been allergic to any component of camrilizumab or to any component of the drug under study
• The researchers consider those who were not suitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Camrelizumab + Apatinib + nab-paclitaxel +S-1; Camrelizumab combined with Apatinib mesylate tablets, nab-paclitaxel and S-1 in the treatment of locally advanced gastric cancer	Drug: Camrelizumab; Camrelizumab One course will last 21 days.Given once every 3 weeks at a dose of 200 mg.; Drug: Apatinib Mesylate; Apatinib One course will last 21 days.Oral administration at a dose of 250 mg everyday。; Drug: nab-paclitaxel; nab-paclitaxel One course will last 21 days。Given twice every 3 weeks at a dose of 125 mg/m2.; Drug: S1; S-1 was calculated according to body surface area , P.O., bid, d1-d14。And the dosage according body surface area:<1.25m2, 40mg every time;1.25-1.5m2,50mg every time; >1.5m2, 60mg every time
Active Comparator: nab-paclitaxel +S-1; nab-paclitaxel and S-1 in the treatment of locally advanced gastric cancer	Drug: nab-paclitaxel; nab-paclitaxel One course will last 21 days。Given twice every 3 weeks at a dose of 125 mg/m2.; Drug: S1; S-1 was calculated according to body surface area , P.O., bid, d1-d14。And the dosage according body surface area:<1.25m2, 40mg every time;1.25-1.5m2,50mg every time; >1.5m2, 60mg every time

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
major pathological response	major pathological response（MPR）	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumours (RECIST) version. 1.1, and immune-related (ir) RECIST	4 months
R0 resection rate	The surgical procedure was total or subtotal gastrectomy with 3 weeks after total neoadjuvant therapy.	4 months
pathological complete response	pathological complete response (pCR)	4 months

Collaborators and Investigators

• Sponsor: Fujian Medical University

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2020
• Primary Completion (Actual): July 22, 2022
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: December 10, 2019
• First Submitted That Met QC Criteria: December 11, 2019
• First Posted (Actual): December 12, 2019

Study Record Updates

• Last Update Posted (Actual): September 7, 2023
• Last Update Submitted That Met QC Criteria: September 3, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Paclitaxel; Apatinib
• Other Study ID Numbers: Arise-FJ-G005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No