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

Bile Duct Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT00624182
• Other study ID #: AUGIS-001
• Status: Suspended
• Phase: Phase 1
• First received: February 19, 2008
• Last updated: June 22, 2015
• Start date: February 2008
• Est. completion date: December 2016

Study information

• Verified date: June 2015
• Source: Akita University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Suspended
• Enrollment: 9
• Est. completion date: December 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Bile Duct Cancer
• Bile Duct Neoplasms
• Cholangiocarcinoma

Intervention

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.

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.

Locations

Country	Name	City	State
Japan	Akita University Hosipital	Akita

Sponsors (2)

Lead Sponsor	Collaborator
Akita University Hospital	Human Genome Center, Institute of Medical Science, University of Tokyo

Country where clinical trial is conducted

Japan, 

References & Publications (7)

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]. — View Citation

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. — View Citation

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. 2005 Jul-Aug;28(4):332-42. — View Citation

Marchand M, van Baren N, Weynants P, Brichard V, Dréno B, Tessier MH, Rankin E, Parmiani G, Arienti F, Humblet Y, Bourlond A, Vanwijck R, Liénard D, Beauduin M, Dietrich PY, Russo V, Kerger J, Masucci G, Jäger 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. — View Citation

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. — View Citation

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. — View Citation

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 Nov;98(11):1803-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety (toxicities as assessed by NCI CTCAE version 3)		5 years
Secondary	URLC10 peptide specific CTL induction		5 years
Secondary	DTH to URLC10 peptide		5 years
Secondary	Changes in levels of regulatory T cells		5 years
Secondary	Objective response rate as assessed by RECIST criteria		5 years
Secondary	Time to progression		5 years
Secondary	Survival rate		5 years