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

Phase 1

Suspended

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Phase I study	Peptide vaccine for URLC10	-
Phase I study	Gemcitabine	-

Primary Outcome Measures

Name	Time	Method
Safety (toxicities as assessed by NCI CTCAE version 3)	5 years

Secondary Outcome Measures

Name	Time	Method
DTH to URLC10 peptide	5 years
URLC10 peptide specific CTL induction	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

Receive instant email notifications about changes in this clinical trial

Receive instant email notifications about changes in this clinical trial