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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02805829
Recruitment Status : Unknown
Verified June 2016 by Junnian Zheng, Xuzhou Medical University.
Recruitment status was:  Not yet recruiting
First Posted : June 20, 2016
Last Update Posted : June 22, 2016
Sponsor:
Information provided by (Responsible Party):
Junnian Zheng, Xuzhou Medical University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Gastric Cancer Drug: Trastuzumab + NK cells Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Combination Trastuzumab With Expanded NK Cells for Treating HER2-positive Gastric Cancer
Study Start Date : January 2017
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Stomach Cancer
Drug Information available for: Trastuzumab

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 Name: Herceptin




Primary Outcome Measures :
  1. Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Number of Participants with tumor recurrence metastasis as a Measure of effectiveness [ Time Frame: 2 years ]

Other Outcome Measures:
  1. T cell subsets figures [ Time Frame: 12 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02805829


Contacts
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Contact: Junnian Zheng, MD 86-0516-83372010 jnzheng@xzmc.edu.cn
Contact: Huizhong Li, MM 86-0516-85582635 lhz@xzmc.edu.cn

Locations
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China, Jiangsu
Xuzhou medical university
Xuzhou, Jiangsu, China, 221002
Sponsors and Collaborators
Xuzhou Medical University
Investigators
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Principal Investigator: Junnian Zheng, MD Xuzhou Medical University
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Responsible Party: Junnian Zheng, professor, Xuzhou Medical University
ClinicalTrials.gov Identifier: NCT02805829    
Other Study ID Numbers: XYFY2016-KL014-01
First Posted: June 20, 2016    Key Record Dates
Last Update Posted: June 22, 2016
Last Verified: June 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Junnian Zheng, Xuzhou Medical University:
NK cells
Trastuzumab
Additional relevant MeSH terms:
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Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Trastuzumab
Antineoplastic Agents, Immunological
Antineoplastic Agents