Gemcitabine With Peptide Vaccine Therapy in Treating Patients With Bile Duct Cancer
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.
Bile Duct Cancer
Biological: Peptide vaccine for URLC10
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 1 Study of Gemcitabine With Vaccine Therapy Targeting Tumor Antigen, URLC10, For The Patients With Unresectable or Recurrent Bile Duct Cancer|
- Safety (toxicities as assessed by NCI CTCAE version 3) [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
- URLC10 peptide specific CTL induction [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- DTH to URLC10 peptide [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Changes in levels of regulatory T cells [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Objective response rate as assessed by RECIST criteria [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Time to progression [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Survival rate [ Time Frame: 5 years ] [ Designated as safety issue: No ]
|Study Start Date:||February 2008|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||April 2016 (Final data collection date for primary outcome measure)|
|Experimental: Phase I study||
Biological: Peptide vaccine for URLC10
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.
Other Name: GemcitabineDrug: Gemcitabine
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.
Other Name: Gemcitabine
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00624182
|Akita University Hosipital|
|Akita, Japan, 010-8543|
|Study Chair:||Yuzo Yamamoto, MD||Department of Gastroenterological Surgery, Akita University, School of Medicine|