Study of OTSGC-A24 Vaccine in Advanced Gastric Cancer

This study is currently recruiting participants.
Verified December 2013 by National University Hospital, Singapore
Sponsor:
Collaborators:
Wakayama Medical University
Severance Hospital
Information provided by (Responsible Party):
National University Hospital, Singapore
ClinicalTrials.gov Identifier:
NCT01227772
First received: October 21, 2010
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

Active vaccination with tumor specific antigens and VEGFR1 HLA-A24 epitopes can improve survival of patients with advanced Gastric Cancer.


Condition Intervention Phase
Gastric Cancer
Biological: OTSGC-A24
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/IIa Study of OTSGC-A24 Vaccine in Advanced Gastric Cancer

Resource links provided by NLM:


Further study details as provided by National University Hospital, Singapore:

Primary Outcome Measures:
  • safety of OTSGC-24 [ Time Frame: within 4 weeks of treatment ] [ Designated as safety issue: Yes ]
    Dose limiting toxicity will be evaluated during the first 4 weeks of treatment. If in the unlikely event that DLT is observed in 1 of the 3 subjects, an additional 3 subjects will be enrolled at the same dose level. If DLT is observed in 2 of the 6 subjects, subsequent cohorts will be treated at 0.5 mg.

  • Optimal dosing schedule [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    In each cohort, OTSGC-A24 (~1 mg) will be administered subcutaneously at 3-weekly (cohort 1), 2-weekly (cohort 2) and weekly (cohort 3) interval. Treatment may continue until the subject experiences confirmed disease progression or unacceptable toxicity, withdraws consent, or requires treatment with another therapeutic modality.


Secondary Outcome Measures:
  • Induction of specific cytotoxic T-lymphocyte (CTL) response [ Time Frame: after 4 weeks and 12 weeks of vaccination ] [ Designated as safety issue: Yes ]
    Up to 10 patients per cohort will be recruited in the cohort or cohorts with the highest specific CTL induction rate to define the optimal dosing schedule for OTSGC-A24.


Estimated Enrollment: 23
Study Start Date: November 2010
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Weekly Cohort
The gastric cancer vaccine (OTSGC-A24) will be administered at a dose of 1 mg once a week
Biological: OTSGC-A24
OTSGC-A24 administered at 1 mg in weekly, 2-weekly, and 3-weekly cohorts.
Experimental: 2-weekly cohort
The gastric cancer vaccine (OTSGC-A24) will be administered at the dose of 1 mg every 2 weeks.
Biological: OTSGC-A24
OTSGC-A24 administered at 1 mg in weekly, 2-weekly, and 3-weekly cohorts.
Experimental: 3-weekly cohort
The gastric cancer vaccine (OTSGC-A24)will be administered at 1 mg very 3 weeks
Biological: OTSGC-A24
OTSGC-A24 administered at 1 mg in weekly, 2-weekly, and 3-weekly cohorts.

Detailed Description:

Although palliative chemotherapy improved the outcome of patients with advanced Gastric Cancer, the prognosis for this group of patients remains poor. Tumor specific antigens and angiogenesis pathway are potential targets for immunotherapy. A cocktail of peptide vaccines is selected to overcome gastric cancer's heterogeneous and enhance the anti-tumor effect. Five HLA-A*2402-binding peptide vaccines derived from tumor specific antigens and VEGFR1 are chosen based on the frequencies of their expressions in gastric cancer and the ability to induce specific cytotoxic T-lymphocytes. In preclinical model, both down regulation these targets with siRNA and active vaccination resulted in tumor regression. The purpose of the study is to evaluate the safety and optimal dosing schedule of a cancer vaccine cocktail, OTSGC-A24 targeting novel specific tumor antigens FOXM1, DEPDC1, KIF20A, URLC10 and VEGFR1 in advanced gastric cancer patients with HLA-2402 haplotype.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed inoperable or metastatic adenocarcinoma of the stomach or lower third of the oesophagus refractory or intolerable to standard therapy.
  • Patients must have measurable or evaluable disease.
  • Age >= 201years
  • ECOG performance status of 0 to 2
  • Life expectancy at least 3 months
  • Patients must have normal organ and marrow function as defined below:
  • absolute neutrophil count >=1,500/mcL
  • platelets >=100,000/mcL
  • total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT) <=2.5 X institutional upper limit of
  • Normal creatinine within normal institutional limits
  • Patients must be HLA-A*2402
  • Patients must have recover from all reversible treatment toxicity from prior chemotherapy, radiotherapy or surgery.
  • The effects of OTSGC-A24 on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Patients receiving any other investigational agents.
  • History of significant gastrointestinal bleeding that required intervention within the prior 1 month is ineligible; inherited bleeding diathesis or coagulopathy.
  • Serious non healing wound and peptic ulcer disease
  • Previous history of intestinal perforation
  • Invasive procedures defined as follows (Insertion of a vascular access device is not considered major/minor surgery):
  • Major surgical procedure, open biopsy or significant traumatic injury =28 days prior to -registration
  • Anticipation of need for major surgical procedures during the course of the study
  • Core biopsy <=7 days
  • Minor surgery <=2 weeks
  • Symptomatic CNS metastasis
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg), symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction/cerebrovascular event (<=6 months prior to study entry), cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, long term systemic immunosuppressant or corticosteroid.
  • Women who are breast-feeding or pregnant are excluded from this study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01227772

Contacts
Contact: Wei Peng Yong, MRCP, MB ChB (65) 6772 4670 Wei_Peng_Yong@nuhs.edu.sg
Contact: Christine Vergara (65) 6772 4619 christine_vergara@nuhs.edu.sg

Locations
Japan
Wakayama Medical University Hospital Recruiting
Wakayama, Japan, 641-8509
Contact: Hiroki Yamaue, M.D.       yamaue-h@wakayama-med.ac.jp   
Principal Investigator: Hiroki Yamaue, M.D.         
Korea, Republic of
Severance Hospital, Yonsei University Health System Recruiting
Seoul, Korea, Republic of, 120-752
Contact: Sun Young Rha, M.D, Ph.D    +82 (2) 2228 8050    rha7655@yuhs.ac   
Contact: Hyun Jung Park    +82 (2) 2228 8054    hjwwjd@yuhs.ac   
Principal Investigator: Sun Young Rha, M.D, Ph.D         
Singapore
National University Hospital Recruiting
Singapore, Singapore
Contact: Wei Peng Yong, MRCP, MB ChB    65 6772 4670    Wei_Peng_Yong@nuhs.edu.sg   
Principal Investigator: Wei Peng Yong, MRCP, MB ChB         
Sponsors and Collaborators
National University Hospital, Singapore
Wakayama Medical University
Severance Hospital
Investigators
Principal Investigator: Wei Peng Yong, MRCP, MB ChB National University Hospital, Singapore
  More Information

Publications:
Responsible Party: National University Hospital, Singapore
ClinicalTrials.gov Identifier: NCT01227772     History of Changes
Other Study ID Numbers: GA04/26/10
Study First Received: October 21, 2010
Last Updated: December 10, 2013
Health Authority: Singapore: Domain Specific Review Boards
Singapore: Health Sciences Authority
Singapore: Ministry of Health

Keywords provided by National University Hospital, Singapore:
gastric cancer vaccine
OTSGC-A24
A Phase I/IIa study
HLA-A24-positive

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases

ClinicalTrials.gov processed this record on April 17, 2014