Dendritic Cell-based Immunotherapy in Treatment Gastric Cancer

Activated Autologous Dendritic Cells by Autologous Tumor Cell Membrane Proteins in Treatment of Gastric Cancer

Study objectives are to investigate the efficacy and safety of activated autologous dendritic cells (DCs) in treatment of gastric cancer. DCs are activated by the proteins from autologous tumor cell membrane and cytokines in vitro. The efficacy endpoints include objective response, immune-cell response, recurrent rate after a radical surgery, progression-free survival and overall survival, and the safety endpoints include adverse events, laboratory tests, ECG, ECOG-PT, etc.

Study Overview

• Status: Unknown
• Conditions: Gastric Cancer
• Intervention / Treatment: Biological: activated DCs; Procedure: radical surgery only

Detailed Description

Study objectives are to investigate the efficacy and safety of activated autologous dendritic cells (DCs) in treatment of gastric cancer. The autologous DCs are collected and enriched from peripheral blood, and then are activated by the proteins from autologous tumor cell membrane and cytokines in vitro. The efficacy endpoints include objective response, immune-cell response, recurrent rate after a radical surgery, progression-free survival and overall survival, and the safety endpoints include adverse events, laboratory tests, ECG, ECOG-PT, etc. All patients will be followed up for at least 2 years after treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Gansu
    • Lanzhou, Gansu, China, 730030
      • Recruiting
      • Lanzhou University Second Hospital
      • Contact: Yumin Li, MD, PhD; Phone Number: +8613893615421; Email: liym@lzu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written informed consent given before any trial-specific procedure is initiated
2. Male or female, at least 18 years of age at the time of informed consent
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
4. Life expectancy >3 months assessed during Screening
5. Documented (histologically- or cytologically-proven) gastric cancer that is can be radially removed

Exclusion Criteria:

1. Non-healing wounds on any part of the body
2. Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 1 month prior to surgery, unless adequately treated and stable
3. Active uncontrolled bleeding or a known bleeding diathesis

4. Significant cardiovascular disease or condition, including:

   1. Congestive heart failure currently requiring therapy
   2. Class III or IV cardiovascular disease according to the New York Heart Association's (NYHA) functional criteria (25)
   3. Need for antiarrhythmic medical therapy for a ventricular arrhythmia
   4. Severe conduction disturbance (e.g., 3rd degree heart block)
   5. Unstable angina pectoris (last episode at least 6 months prior to surgery)
   6. Uncontrolled hypertension (per the Investigator's discretion)
   7. Myocardial infarction within 6 months prior to C1/D1

5. Abnormal hematologic, renal or hepatic function as defined by the following criteria:

   1. Absolute neutrophil count (ANC) <1.5 ×109/L (1500/mm3)
   2. Hemoglobin ≤9 g/dL
   3. Platelet count <75 ×109/L (75,000/mm3)
   4. Serum creatinine >1.5 × upper limit of normal (ULN) for the institution
   5. Aspartate aminotransferase (AST) >3.5 × ULN for the institution or AST >5 × ULN for the institution in case of known liver metastases
   6. Alanine aminotransferase (ALT) >3.5 × ULN for the institution or ALT >5 × ULN for the institution in case of known liver metastases
   7. Total bilirubin >1.5 × ULN for the institution
   8. Prothrombin time as assessed by International Normalized Ratio (INR) >1.5 × ULN for the institution*
   9. Partial thromboplastin time (PTT) >1.5 × ULN for the institution*

6. Any of the following within 2 weeks prior to surgery:

   1. Any serious or uncontrolled infection
   2. Any infection requiring parenteral antibiotics
   3. Unexplained fever >38.0 °C
7. Any other life-threatening illness, significant organ system dysfunction, or clinically significant laboratory abnormality, which in the opinion of the Investigator, would either compromise the patient's safety or interfere with the evaluation of the safety of the trial treatment
8. Any kind of disorder that compromises the ability of the patient to give written informed consent and/or to comply with trial procedures or is unwilling or unable to comply with trial requirements at the discretion of the Investigator
9. Breast feeding, or plans by the patient (or the patient's partner) to become pregnant during treatment or within 4 months after the end of treatment

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radical surgery plus activated DCs; In 21 days after a radical surgery, activated DCs are iv infused	Biological: activated DCs; autologous dendritic cells are collected and enriched from 50 ml of peripheral blood, then activated by autologous tumor cell membrane proteins. Then the activated DCs are iv infused in 21 days after a radical surgery.; Other Names: activated DCs by autologous tumor cell membrane proteins; Procedure: radical surgery only; Only radical surgery is given to the control group
Active Comparator: Radical surgery only; Radical surgery only group as a control group	Procedure: radical surgery only; Only radical surgery is given to the control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression-free survival	Time to progression/death or censored time	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
recurrent rate	the rate of cancer recurring after surgery	3 years
overall survival rate	time to death or censored time	5 years
immune-cells response	CD4/CD8 T lymphocyte percentage change	3 months
Adverse event rate	Adverse event rate	3 months

Collaborators and Investigators

• Sponsor: LanZhou University
• Investigators: Principal Investigator: Yumin Li, Lanzhou University Second Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Anticipated): July 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: January 16, 2018
• First Submitted That Met QC Criteria: January 24, 2018
• First Posted (Actual): January 25, 2018

Study Record Updates

• Last Update Posted (Actual): January 25, 2018
• Last Update Submitted That Met QC Criteria: January 24, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: immunotherapy; dendritic cell; tumor cell membrane proteins
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: LAUDC 2017001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: we'll update the registration system. But final data will be summarized and published in a medical journal

Drug and device information, study documents

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