Gemcitabine With Peptide Vaccine Therapy in Treating Patients With Bile Duct Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety, tolerability, and immune response of different doses of URLC10 peptide emulsified with Montanide ISA51 in combination with gemcitabine. Recommended phase II dose will be also determined.

Detailed Description
-----------------
Our previous studies have demonstrated that up-regulated lung cancer 10 (URLC10) has been identified as a new target of tumor associated antigen using cDNA microarray technique combined with the expression profiles of normal and cancer tissues. We have also found that 100% of tissue samples from bile duct cancer express URLC10. We have determined the HLA-A*2402 and HLA-A*0201 restricted epitope peptides derived from URLC10.These epitope peptides have shown to induce specific Cytotoxic T Lymphocytes (CTL). Furthermore, 60% and 20% of Japanese population have HLA-A*2402 and HLA-A*0201, respectively. Therefore, these peptides are suitable for clinical trial. On the other hand, gemcitabine is a drug approved against bile duct cancer. Recent studies has reported that gemcitabine has an additional ability to improve immune response. From these results, synergistic effect between vaccine therapy and chemotherapy using gemcitabine will be expected. In this clinical trial, we evaluate the safety, tolerability, and immune responses of different doses of URLC10 peptide emulsified with Montanide ISA51 as immunochemotherapy in the patients with unresectable or recurrent bile duct cancer. Toxicity profiles will be monitored, and antigen specific T cell responses will be described.

Official Title
-----------------
Phase 1 Study of Gemcitabine With Vaccine Therapy Targeting Tumor Antigen, URLC10, For The Patients With Unresectable or Recurrent Bile Duct Cancer

Conditions
-----------------
Bile Duct Cancer

Intervention / Treatment
-----------------
* Biological: Peptide vaccine for URLC10
* Drug: Gemcitabine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: DISEASE CHARACTERISTICS Advanced bile duct cancer precluding curative surgical resection and recurrent bile duct cancer measurable disease by CT scan, ultrasonography, or other imaging modalities. PATIENTS CHARACTERISTICS ECOG performance status 0-2 Life expectancy >3 months Laboratory values as follows 2,000/mm³< WBC < 15,000/mm³ Platelet count ≥ 75,000/mm³ 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 HLA-A*2402 or HLA-A*0201 Able and willing to give valid written informed consent Exclusion Criteria: Pregnancy (women of childbearing potential: Refusal or inability to use effective means of contraception) Breastfeeding Serious or uncontrolled infection Prior chemotherapy (except gemcitabine), radiation therapy, or immunotherapy within 4 weeks. Other malignancy within 5 years prior to entry into the study Concomitant treatment with steroids or immunosuppressing agent Disease to the central nervous system Decision of unsuitableness by principal investigator or physician-in-charge

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase I study<br> | Biological: Peptide vaccine for URLC10<br>* Increasing the doses of URLC10 peptides will be administered by subcutaneous injection on day 1, 8, 15, and 22 of each 28-day treatment cycles. Doses of 0.5, 1.0, 2.0mg/body are planned. Repeated cycles of this therapy will be continued until patients develop progressive disease or unacceptable toxicity, or maximum 2 cycles, whichever occurs first.<br>* Other names: Gemcitabine;Drug: Gemcitabine<br>* Gemcitabine will be administered intravenously at a fixed dose of 1000mg/m2 on day 1, 8, and 15. Repeated cycles of this therapy will be continued until patients develop progressive disease or unacceptable toxicity, or maximum 2 cycles, whichever occurs first.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (toxicities as assessed by NCI CTCAE version 3) |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| URLC10 peptide specific CTL induction |  | 5 years | 
| DTH to URLC10 peptide |  | 5 years | 
| Changes in levels of regulatory T cells |  | 5 years | 
| Objective response rate as assessed by RECIST criteria |  | 5 years | 
| Time to progression |  | 5 years | 
| Survival rate |  | 5 years |