Safety Study of Multiple Peptide Vaccine to Esophageal Cancer

Phase 1 Study of Multiple Peptide Vaccine Therapy and GM-CSF in Treating Patients With Esophageal Cancer

This is a phase 1 study of multiple peptide vaccine therapy and GM-CSF in treating patients with esophageal cancer.

Study Overview

• Status: Completed
• Conditions: Esophageal Cancer
• Intervention / Treatment: Biological: LY6K, VEGFR1, VEGFR2

Detailed Description

LY6K (lymphocyte antigen 6 complex, locus K) was identified as a new target of tumor associated antigen using cDNA microarray technologies combined with the expression profiles of normal and cancer tissues. On the other hand, anti-angiogenic therapy is now considered to be one of promising approaches to treat of cancer. In this clinical trial, we evaluate the safety and immune responses of multiple peptide cocktail including LY6K and vascular endothelial growth factor receptor 1 (VEGFR1) and vascular endothelial growth factor receptor 2 (VEGFR2) together with IFA and GM-CSF as immunoadjuvants in patients who had LY6K expressed primary esophageal cancer. Toxicity profiles will be monitored, and antigen specific T cell responses will be described.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan, 135-8550
    • Takuya Takayama M.D.Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must have metastatic disease of esophageal cancer, and treatment has failed, or in the situation where effective therapy is not available, or has been refused due to severe adverse effects of chemotherapy
2. WHO performance status of 0 to 2
3. Age ≥ 20 years, ≤75 years
4. Chemotherapy, any type of radiation therapy, or immunotherapy within 4 weeks before study entry
5. Expected survival of at least 3 months
6. WBC≥ 2,000/mm³ Platelet count ≥ 100,000/mm³ Total bilirubin ≤ 1.5 x the institutional normal upper limits AST, ALT, ALP ≤ 2.5 x the institutional normal upper limits Creatinine ≤ 1.5 x the institutional normal upper limits
7. Patients must be HLA-A2402
8. Primary lesion of esophageal cancer must express LY6K
9. Able and willing to give valid written informed consent

Exclusion Criteria:

1. Pregnancy (women of childbearing potential: Refusal or inability to use effective means of contraception)
2. Breastfeeding
3. Serious infections requiring antibiotics
4. Patient with peptic ulcer disease
5. Previous history of intestinal perforation
6. bleeding disorders (INR ≥ 1.5)
7. Necessity of drug-mediated inhibition with platelet function
8. Taking antithrombogenic agents within 10 days
9. Serious hypertension
10. Previous history of arterial thrombosis or venous thrombosis
11. Other malignancy within 5 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ
12. Clinically significant heart disease or previous history of myocardial infarction within the past 12 months
13. Concomitant treatment with steroids or immunosuppressing agent
14. Disease to the central nervous system
15. Decision of unsuitableness by principal investigator or physician-in-charge

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Toxicity of multiple peptide vaccinations	one year

Secondary Outcome Measures

Outcome Measure	Time Frame
Immune responses including LY6K, VEGFR1 and VEGFR2 specific T cells	one year

Collaborators and Investigators

• Sponsor: Japanese Foundation for Cancer Research
• Collaborators: Human Genome Center, Institute of Medical Science, University of Tokyo
• Investigators: Principal Investigator: Takuya Takayama, M.D.Ph.D, Cancer Institute of Japanese Foundation for Cancer Research

Publications and helpful links

General Publications

• Suda T, Tsunoda T, Daigo Y, Nakamura Y, Tahara H. Identification of human leukocyte antigen-A24-restricted epitope peptides derived from gene products upregulated in lung and esophageal cancers as novel targets for immunotherapy. Cancer Sci. 2007 Nov;98(11):1803-8. doi: 10.1111/j.1349-7006.2007.00603.x.
• Ishizaki H, Tsunoda T, Wada S, Yamauchi M, Shibuya M, Tahara H. Inhibition of tumor growth with antiangiogenic cancer vaccine using epitope peptides derived from human vascular endothelial growth factor receptor 1. Clin Cancer Res. 2006 Oct 1;12(19):5841-9. doi: 10.1158/1078-0432.CCR-06-0750.
• Wada S, Tsunoda T, Baba T, Primus FJ, Kuwano H, Shibuya M, Tahara H. Rationale for antiangiogenic cancer therapy with vaccination using epitope peptides derived from human vascular endothelial growth factor receptor 2. Cancer Res. 2005 Jun 1;65(11):4939-46. doi: 10.1158/0008-5472.CAN-04-3759.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: November 14, 2007
• First Submitted That Met QC Criteria: November 19, 2007
• First Posted (Estimate): November 20, 2007

Study Record Updates

• Last Update Posted (Estimate): July 15, 2008
• Last Update Submitted That Met QC Criteria: July 10, 2008
• Last Verified: July 1, 2008

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; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms
• Other Study ID Numbers: TB-454