Combination of Chemoradiation Therapy and Epitope Peptide Vaccine Therapy in Treating Patients With Esophageal Cancer - Full Text View

Purpose

The purpose of this study is to evaluate the safety and immune response of multiple peptides (URLC10, TTK, KOC1 VEGFR1, and VEGFR2) emulsified with Montanide ISA51 in combination with chemotherapy (CDDP, 5-FU) plus radiation therapy in treating patients with unresectable, advanced or recurrent esophageal cancer.

Condition	Intervention	Phase
Esophageal Cancer	Biological: URLC10, TTK, KOC1, VEGFR1, VEGFR2, cisplatin, fluorouracil	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 I Study of Chemoradiation Therapy With Epitope Peptide Vaccine Therapy in Treating Patients With Unresectable, Advanced or Recurrent Esophageal Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders

Drug Information available for: Fluorouracil Cisplatin

U.S. FDA Resources

Further study details as provided by Teikyo University:

Primary Outcome Measures:

Safety(toxicities as assessed by NCI CTCAE version3) [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Peptide specific CTL induction [ Time Frame: 3 months ] [ Designated as safety issue: No ]
DTH to peptide [ Time Frame: 3 months ] [ Designated as safety issue: No ]
Changes in levels of regulatory T cells [ Time Frame: 3 months ] [ Designated as safety issue: No ]
Objective response rate as assessed by RECIST criteria [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Time to progression [ Time Frame: 1 year ] [ Designated as safety issue: No ]
survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment:	9
Study Start Date:	February 2008
Estimated Study Completion Date:	March 2012
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	Biological: URLC10, TTK, KOC1, VEGFR1, VEGFR2, cisplatin, fluorouracil Escalating dose of multiple peptides (URLC10, TTK, KOC1 VEGFR1, and VEGFR2) emulsified with Montanide ISA51 will be administered by subcutaneous injection on days 15, 22, 28 and 35 of treatment cycle. Doses of each peptide are planning 0.5mg, 1mg and 3mg/body. Chemotherapy plus radiation therapy will be done as follows: fluorouracil (400mg/m2) on day1-5 and 8-12, cisplatin (40mg/m2) on days 1 and 8, radiation (2Gy) on days 1-5, 8-12 and 15-19. Two cycles of combination of chemoradiation therapy and epitope peptide vaccine therapy will be done. Other Names: CDDP 5-FU

Arms

Assigned Interventions

Experimental: 1

Biological: URLC10, TTK, KOC1, VEGFR1, VEGFR2, cisplatin, fluorouracil

Escalating dose of multiple peptides (URLC10, TTK, KOC1 VEGFR1, and VEGFR2) emulsified with Montanide ISA51 will be administered by subcutaneous injection on days 15, 22, 28 and 35 of treatment cycle. Doses of each peptide are planning 0.5mg, 1mg and 3mg/body. Chemotherapy plus radiation therapy will be done as follows: fluorouracil (400mg/m2) on day1-5 and 8-12, cisplatin (40mg/m2) on days 1 and 8, radiation (2Gy) on days 1-5, 8-12 and 15-19. Two cycles of combination of chemoradiation therapy and epitope peptide vaccine therapy will be done.

Other Names:

CDDP
5-FU

Detailed Description:

Up-regulated ling cancer 10 (URLC10), TTK protein kinase (TTK) and K homology domain containing protein over expressed in cancer (KOC1) were identified as new targets of tumor associated antigens using cDNA microarray technologies combined with the expression profiles of normal and cancer tissues. Furthermore, anti-angiogenic therapy is now considered to be one of promising approaches for treating cancer. Vascular endothelial growth factor receptor 1 (VEGFR1) and vascular endothelial growth factor receptor 2 (VEGFR2) are essential targets for tumor angiogenesis. Epitope peptides for these targets are able to induce cytotoxic T lymphocytes (CTL) restricted to HLA-A *2402 in vivo. On the other hand, chemotherapy (CDDP, 5-FU) plus radiation therapy has been to be a standard treatment for unresectable advanced esophageal cancer. In this clinical trial, we evaluate the safety and immune responses of different doses of multiple peptides (URLC10, TTK, KOC1, VEGFR1, and VEGFR 2) emulsified with Montanide ISA 51 in combination with chemotherapy (CDDP, 5-FU) plus radiation therapy in treating patients with unresectable, advanced or recurrent esophageal cancer.

Eligibility

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

Criteria

Inclusion Criteria:

Patients must have unresectable, locally advanced, recurrent or metastatic disease of esophageal cancer.
measurable disease by CT scan
ECOG performance status of 0 to 2
Expected survival of at lease 3months
Patients must be HLA-A2402
Laboratory values as follow:
- WBC > 2000/mm3,
- Platelet count > 75000/mm3,
- Total bilirubin < 1.5 x the institutional normal upper limits,
- Creatinine < 1.5 x the institutional normal upper limits,
- AST. ALT. ALP < 2.5 x the institutional normal upper limits
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
Active or uncontrolled infection
Prior chemotherapy,radiation therapy or immunotherapy within 4 weeks
Concurrent treatment with steroid or immunosuppressing agent
Patient with peptic ulcer disease
Active or uncontrolled other malignancy
Other malignancy within 5 years prior to entry into the study, expect for treated non-melanoma skin cancer and cervical carcinoma in situ
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: NCT00632333

Contacts

Contact: Hisae Iinuma, PhD

+81-33-964-1211

iinuma@med.teikyo-u.ac.jp

Locations

Japan
Teikyo University	Recruiting
2-11-1 Kaga Itabashi-ku, Tokyo, Japan, 173-0003
Contact: Hisae Iinuma, PhD +81-33-964-1211 iinuma@med.teikyo-u.ac.jp
Principal Investigator: Hisae Iinuma, PhD

Sponsors and Collaborators

Teikyo University

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

Investigators

Study Chair:

Kota Okinaga, MD, PhD

Teikyo University , Department Surgery

More Information

Publications:

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Nakopoulou L, Stefanaki K, Panayotopoulou E, Giannopoulou I, Athanassiadou P, Gakiopoulou-Givalou H, Louvrou A. Expression of the vascular endothelial growth factor receptor-2/Flk-1 in breast carcinomas: correlation with proliferation. Hum Pathol. 2002 Sep;33(9):863-70.

Suda T, Tsunoda T, Uchida N, Watanabe T, Hasegawa S, Satoh S, Ohgi S, Furukawa Y, Nakamura Y, Tahara H. Identification of secernin 1 as a novel immunotherapy target for gastric cancer using the expression profiles of cDNA microarray. Cancer Sci. 2006 May;97(5):411-9.

Watanabe T, Suda T, Tsunoda T, Uchida N, Ura K, Kato T, Hasegawa S, Satoh S, Ohgi S, Tahara H, Furukawa Y, Nakamura Y. Identification of immunoglobulin superfamily 11 (IGSF11) as a novel target for cancer immunotherapy of gastrointestinal and hepatocellular carcinomas. Cancer Sci. 2005 Aug;96(8):498-506.

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.

Ishida K, Ando N, Yamamoto S, Ide H, Shinoda M. Phase II study of cisplatin and 5-fluorouracil with concurrent radiotherapy in advanced squamous cell carcinoma of the esophagus: a Japan Esophageal Oncology Group (JEOG)/Japan Clinical Oncology Group trial (JCOG9516). Jpn J Clin Oncol. 2004 Oct;34(10):615-9. Erratum in: Jpn J Clin Oncol. 2005 Feb;35(2):108.

Waters JS, Tait D, Cunningham D, Padhani AR, Hill ME, Falk S, Lofts F, Norman A, Oates J, Hill A. A multicentre phase II trial of primary chemotherapy with cisplatin and protracted venous infusion 5-fluorouracil followed by chemoradiation in patients with carcinoma of the oesophagus. Ann Oncol. 2002 Nov;13(11):1763-70.

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.

Responsible Party:	Department of Surgery, Teikyo University
ClinicalTrials.gov Identifier:	NCT00632333 History of Changes
Other Study ID Numbers:	TPR07-079
Study First Received:	February 29, 2008
Last Updated:	July 20, 2011
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Keywords provided by Teikyo University:

Epitope peptide
Vaccination
Chemoradiation
Esophageal cancer

Additional relevant MeSH terms:

Esophageal Diseases
Esophageal Neoplasms
Gastrointestinal Diseases
Digestive System Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Cisplatin
Fluorouracil

Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on June 18, 2013