Gemcitabine With Peptide Vaccine Therapy in Treating Patients With Bile Duct Cancer - Full Text View

Purpose

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.

Condition	Intervention	Phase
Bile Duct Cancer	Biological: Peptide vaccine for URLC10 Drug: Gemcitabine	Phase 1

Study Type:	Interventional
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Gemcitabine Gemcitabine hydrochloride

U.S. FDA Resources

Further study details as provided by Akita University Hospital:

Primary Outcome Measures:

Safety (toxicities as assessed by NCI CTCAE version 3) [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

URLC10 peptide specific CTL induction [ Time Frame: 4 years ] [ Designated as safety issue: No ]
DTH to URLC10 peptide [ Time Frame: 4 years ] [ Designated as safety issue: No ]
Changes in levels of regulatory T cells [ Time Frame: 4 years ] [ Designated as safety issue: No ]
Objective response rate as assessed by RECIST criteria [ Time Frame: 4 years ] [ Designated as safety issue: No ]
Time to progression [ Time Frame: 4 years ] [ Designated as safety issue: No ]
Survival rate [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	9
Study Start Date:	February 2008
Estimated Study Completion Date:	August 2012
Estimated Primary Completion Date:	June 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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: Gemcitabine Drug: 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

Arms

Assigned Interventions

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: Gemcitabine

Drug: 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

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

Ages Eligible for Study:	20 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00624182

Contacts

Contact: Yuzo Yamamoto, MD	+81-18-884-6123	yy@med.akita-u.ac.jp
Contact: Hiroshi Uchinami, MD	+81-18-884-6215	huchi@gipc.akita-u.ac.jp

Locations

Japan
Akita University Hosipital	Recruiting
1-1-1 Hondo, Akita, Akita, Japan, 010-8543
Contact: Yuzo Yamamoto, MD +81-18-884-6123 yy@med.akita-u.ac.jp
Principal Investigator: Hiroshi Uchinami, MD

Sponsors and Collaborators

Akita University Hospital

Human Genome Center, Institute of Medical Science, University of Tokyo

Investigators

Study Chair:

Yuzo Yamamoto, MD

Department of Gastroenterological Surgery, Akita University, School of Medicine

More Information

Publications:

Date Y, Kimura A, Kato H, Sasazuki T. DNA typing of the HLA-A gene: population study and identification of four new alleles in Japanese. Tissue Antigens. 1996 Feb;47(2):93-101.

Dauer M, Herten J, Bauer C, Renner F, Schad K, Schnurr M, Endres S, Eigler A. Chemosensitization of pancreatic carcinoma cells to enhance T cell-mediated cytotoxicity induced by tumor lysate-pulsed dendritic cells. J Immunother (1997). 2005 Jul-Aug;28(4):332-42.

Correale P, Cusi MG, Del Vecchio MT, Aquino A, Prete SP, Tsang KY, Micheli L, Nencini C, La Placa M, Montagnani F, Terrosi C, Caraglia M, Formica V, Giorgi G, Bonmassar E, Francini G. Dendritic cell-mediated cross-presentation of antigens derived from colon carcinoma cells exposed to a highly cytotoxic multidrug regimen with gemcitabine, oxaliplatin, 5-fluorouracil, and leucovorin, elicits a powerful human antigen-specific CTL response with antitumor activity in vitro. J Immunol. 2005 Jul 15;175(2):820-8. Erratum in: J Immunol. 2005 Nov 1;175(9):6235. Prete, Salvatore [corrected to Prete, Salvatore Pasquale].

Suda T, Tsunoda T, Daigo Y, Nakamura Y, Tahara H. Identification of human leukocyte antigen-A24-restricted epitope peptides derived from gene products upregulated in lung and esophageal cancers as novel targets for immunotherapy. Cancer Sci. 2007 Sep 2; [Epub ahead of print]

Obama K, Ura K, Li M, Katagiri T, Tsunoda T, Nomura A, Satoh S, Nakamura Y, Furukawa Y. Genome-wide analysis of gene expression in human intrahepatic cholangiocarcinoma. Hepatology. 2005 Jun;41(6):1339-48.

Marchand M, van Baren N, Weynants P, Brichard V, Dreno B, Tessier MH, Rankin E, Parmiani G, Arienti F, Humblet Y, Bourlond A, Vanwijck R, Lienard D, Beauduin M, Dietrich PY, Russo V, Kerger J, Masucci G, Jager E, De Greve J, Atzpodien J, Brasseur F, Coulie PG, van der Bruggen P, Boon T. Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1. Int J Cancer. 1999 Jan 18;80(2):219-30.

Rosenberg SA, Yang JC, Schwartzentruber DJ, Hwu P, Marincola FM, Topalian SL, Restifo NP, Dudley ME, Schwarz SL, Spiess PJ, Wunderlich JR, Parkhurst MR, Kawakami Y, Seipp CA, Einhorn JH, White DE. Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nat Med. 1998 Mar;4(3):321-7.

Responsible Party:	Hiroshi Uchinami, Gastroenterological Surgery, Akita University Hospital
ClinicalTrials.gov Identifier:	NCT00624182 History of Changes
Other Study ID Numbers:	AUGIS-001
Study First Received:	February 19, 2008
Last Updated:	February 7, 2012
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:

Bile Duct Neoplasms
Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites

Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on June 17, 2013