Clinical trial NCT00624182: Gemcitabine With Peptide Vaccine Therapy in Treating Patients With Bile Duct Cancer
Official title: Phase 1 Study of Gemcitabine With Vaccine Therapy Targeting Tumor Antigen, URLC10, For The Patients With Unresectable or Recurrent Bile Duct Cancer
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE1
Conditions: Bile Duct Cancer
Lead sponsor: Akita University Hospital
Sponsor class: OTHER
Collaborators: name: Human Genome Center, Institute of Medical Science, University of Tokyo
First posted: 2008-02-26
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, 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.

Eligibility criteria: Inclusion Criteria:

DISEASE CHARACTERISTICS

1. Advanced bile duct cancer precluding curative surgical resection and recurrent bile duct cancer
2. measurable disease by CT scan, ultrasonography, or other imaging modalities.

PATIENTS CHARACTERISTICS

1. ECOG performance status 0-2
2. Life expectancy \>3 months
3. 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
4. HLA-A\*2402 or HLA-A\*0201
5. 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 or uncontrolled infection
4. Prior chemotherapy (except gemcitabine), radiation therapy, or immunotherapy within 4 weeks.
5. Other malignancy within 5 years prior to entry into the study
6. Concomitant treatment with steroids or immunosuppressing agent
7. Disease to the central nervous system
8. Decision of unsuitableness by principal investigator or physician-in-charge

Primary outcomes:
measure: Safety (toxicities as assessed by NCI CTCAE version 3)
timeFrame: 5 years
Secondary outcomes:
measure: URLC10 peptide specific CTL induction
timeFrame: 5 years
measure: DTH to URLC10 peptide
timeFrame: 5 years
measure: Changes in levels of regulatory T cells
timeFrame: 5 years
measure: Objective response rate as assessed by RECIST criteria
timeFrame: 5 years
measure: Time to progression
timeFrame: 5 years
measure: Survival rate
timeFrame: 5 years
Other outcomes:
Locations:
city: Akita
country: Japan
facility: Akita University Hosipital
Study officials:
affiliation: Department of Gastroenterological Surgery, Akita University, School of Medicine
name: Yuzo Yamamoto, MD
role: STUDY_CHAIR
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