Clinical trial NCT00632333: Combination of Chemoradiation Therapy and Epitope Peptide Vaccine Therapy in Treating Patients With Esophageal Cancer
Official title: Phase I Study of Chemoradiation Therapy With Epitope Peptide Vaccine Therapy in Treating Patients With Unresectable, Advanced or Recurrent Esophageal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Esophageal Cancer
Keywords: Epitope peptide
Vaccination
Chemoradiation
Esophageal cancer
Lead sponsor: Teikyo University
Sponsor class: OTHER
Collaborators: name: Human Genome Center, Institute of Medical Science, University of Tokyo
First posted: 2008-03-10
Enrollment: 9
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and immune response of multiple peptides (URLC10, TTK, KOC1 VEGFR1, and VEGFR2) emulsified with Montanide ISA51 in combination with chemotherapy (CDDP, 5-FU) plus radiation therapy in treating patients with unresectable, advanced or recurrent esophageal cancer.

Detailed description: Up-regulated ling cancer 10 (URLC10), TTK protein kinase (TTK) and K homology domain containing protein over expressed in cancer (KOC1) were identified as new targets of tumor associated antigens using cDNA microarray technologies combined with the expression profiles of normal and cancer tissues. Furthermore, anti-angiogenic therapy is now considered to be one of promising approaches for treating cancer. Vascular endothelial growth factor receptor 1 (VEGFR1) and vascular endothelial growth factor receptor 2 (VEGFR2) are essential targets for tumor angiogenesis. Epitope peptides for these targets are able to induce cytotoxic T lymphocytes (CTL) restricted to HLA-A \*2402 in vivo. On the other hand, chemotherapy (CDDP, 5-FU) plus radiation therapy has been to be a standard treatment for unresectable advanced esophageal cancer. In this clinical trial, we evaluate the safety and immune responses of different doses of multiple peptides (URLC10, TTK, KOC1, VEGFR1, and VEGFR 2) emulsified with Montanide ISA 51 in combination with chemotherapy (CDDP, 5-FU) plus radiation therapy in treating patients with unresectable, advanced or recurrent esophageal cancer.

Eligibility criteria: Inclusion Criteria:

1. Patients must have unresectable, locally advanced, recurrent or metastatic disease of esophageal cancer.
2. measurable disease by CT scan
3. ECOG performance status of 0 to 2
4. Expected survival of at lease 3months
5. Patients must be HLA-A2402
6. Laboratory values as follow:

   * WBC \> 2000/mm3,
   * Platelet count \> 75000/mm3,
   * Total bilirubin \< 1.5 x the institutional normal upper limits,
   * Creatinine \< 1.5 x the institutional normal upper limits,
   * AST. ALT. ALP \< 2.5 x the institutional normal upper limits
7. 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. Active or uncontrolled infection
4. Prior chemotherapy,radiation therapy or immunotherapy within 4 weeks
5. Concurrent treatment with steroid or immunosuppressing agent
6. Patient with peptic ulcer disease
7. Active or uncontrolled other malignancy
8. Other malignancy within 5 years prior to entry into the study, expect for treated non-melanoma skin cancer and cervical carcinoma in situ
9. Disease to the central nervous system
10. Decision of unsuitableness by principal investigator or physician-in-charge

Primary outcomes:
measure: Safety(toxicities as assessed by NCI CTCAE version3)
timeFrame: 3 months
Secondary outcomes:
measure: Peptide specific CTL induction
timeFrame: 3 months
measure: DTH to peptide
timeFrame: 3 months
measure: Changes in levels of regulatory T cells
timeFrame: 3 months
measure: Objective response rate as assessed by RECIST criteria
timeFrame: 1 year
measure: Time to progression
timeFrame: 1 year
measure: survival
timeFrame: 1 year
Other outcomes:
Locations:
city: 2-11-1 Kaga Itabashi-ku
country: Japan
facility: Teikyo University
state: Tokyo
Study officials:
affiliation: Teikyo University , Department Surgery
name: Kota Okinaga, MD, PhD
role: STUDY_CHAIR
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