Combination Trastuzumab With Expanded Natural Killer Cells for Treating HER2-positive Gastric Cancer

Combination Trastuzumab With Expanded NK Cells for Treating HER2-positive Gastric Cancer

This trial is to evaluate the safety and effectiveness of activated and expanded in vitro autologous NK cells following trastuzumab treatment for patients Human Epidermal Receptor-2 overexpressing advanced gastric cancer.

Study Overview

• Status: Unknown
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: Trastuzumab + NK cells

Detailed Description

Tumor antigen-specific monoclonal antibodies, block oncogenic signaling and induce Fcγ receptor (FcγR)-mediated cytotoxicity, are considered to be one of the most successful strategies in cancer therapy. Trastuzumab, a monoclonal antibody directed against HER2, was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric cancer. The use of cellular immunotherapy has increased significantly over the past two decades. Natural killer cells are lymphocytes of the innate immune system that have the ability to recognize and kill malignant cells. There is growing evidence show antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells contributes to the efficacy of Herceptin. Therefore, methods to enhance ADCC, such as stimulating the innate immune response, may clinically translate to improved antitumor activity. In this study, the investigators sought to enhance the clinical activity of trastuzumab, administrated in combination with expanded autologous NK cells. The enrolled patients are diagnosed HER2+ advanced gastric cancer. The eligible patient will administrate herceptin on 2 days prior to blood collection. The initial dose of herceptin is 8 mg/kg over 90 minutes IV infusion. On day 0 peripheral blood mononuclear cells were separated from 40-50ml blood by density gradient centrifugation. Then were cultured with human NK cell culture medium and stimulation cytokines in a humidified, 5% carbon dioxide incubator for about 14 days. After NK expansion and verification that the resulting NK cells meet purity, gram stain, and endotoxin release criteria, NK cells were washed and resuspended in isotonic sodium chloride. NK cellular therapy conduct 2 cycles per year. The maintenance dose of herceptin monotherapy is 6 mg/kg over 30 to 90 minutes IV infusion every 3 weeks. This study will determine the safety and efficacy of this novel combinational therapeutic strategy in HER2 positive gastric cancer.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Junnian Zheng, MD; Phone Number: 86-0516-83372010; Email: jnzheng@xzmc.edu.cn
• Study Contact Backup: Name: Huizhong Li, MM; Phone Number: 86-0516-85582635; Email: lhz@xzmc.edu.cn

Study Locations

• China
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221002
      • Xuzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age equal to 18 years or older;
• Patients with histologically confirmed HER2 positive advanced gastric cancer through immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH);
• Normal marrow hematopoiesis function: Hemoglobin≥90g/L, White Blood Cell count≥4000/μL, absolute Neutrophil Cell count (ANC)≥1500/μL, Platelet≥100000/μL;
• Normal important organ function: Total bilirubin≤1.5-fold institutional upper limit of normal (ULN), Aspartate aminotransferase and Alanine aminotransferase≤2.5-fold ULN, Creatinine clearance≥80mL/min;
• Life expectancy≥6 months;
• No other serious heart, lung, kidney dysfunction;
• Quality of life (Karnofsky performance score)≥60;
• Patient must be able to understand and be willing to sign a written informed consent document.

Exclusion Criteria:

• Prior allergic reaction or hypersensitivity to cytokines (eg.Interleukin-2);
• Patients with systemic or local infection requiring anti-infections treatment;
• Patients currently treated with systemic immunosuppressive agents, including steroids;
• Patients with active autoimmune disease or history of transplantation requiring steroid treatment;
• Tested positive for HIV;
• Pregnant or lactating women;
• Patients with coagulation disorders;
• Patients with important organ dysfunction, including cardiac, lung, liver;
• Patients experiencing a cardiac events (acute coronary syndrome, myocardial infarction or ischemia) within the 3 months;
• Any reason that, in the opinion of the investigator, contraindicates that the patient participates in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Trastuzumab + NK cells; On Cycle 1,day -2, patients will receive IV loading dose 8mg/Kg trastuzumab, followed by collection blood on day 0. After NK expansion and verification that the resulting NK cells meet release criteria, NK cells were washed and resuspended in isotonic sodium chloride for intravenous transfusion on day 14. NK cellular therapy conduct 2 cycles per year. The maintenance dose of trastuzumab monotherapy is 6 mg/kg over 30 to 90 minutes IV infusion every 3 weeks till to disease progress.

Drug: Trastuzumab + NK cells; NK cellular therapy conduct 2 cycles per year. Herceptin initial dose of 8 mg/kg over 90 minutes IV infusion, followed by 6 mg/kg over 30 to 90 minutes IV infusion every 3 weeks till to disease progress.; Other Names: Herceptin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with tumor recurrence metastasis as a Measure of effectiveness	2 years

Other Outcome Measures

Outcome Measure	Time Frame
T cell subsets figures	12 weeks

Collaborators and Investigators

• Sponsor: Xuzhou Medical University
• Investigators: Principal Investigator: Junnian Zheng, MD, Xuzhou Medical University

Study record dates

Study Major Dates

• Study Start: January 1, 2017
• Primary Completion (Anticipated): January 1, 2020
• Study Completion (Anticipated): January 1, 2020

Study Registration Dates

• First Submitted: June 15, 2016
• First Submitted That Met QC Criteria: June 15, 2016
• First Posted (Estimate): June 20, 2016

Study Record Updates

• Last Update Posted (Estimate): June 22, 2016
• Last Update Submitted That Met QC Criteria: June 20, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Trastuzumab; NK cells
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: XYFY2016-KL014-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No