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Combination of Chemoradiation Therapy and Epitope Peptide Vaccine Therapy in Treating Patients With Esophageal Cancer

Primary Purpose

Esophageal Cancer

Status

Unknown status

Phase

Phase 1

Locations

Japan

Study Type

Interventional

Intervention

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

About this trial

This is an interventional treatment trial for Esophageal Cancer focused on measuring Epitope peptide, Vaccination, Chemoradiation, Esophageal cancer

Eligibility Criteria

20 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Teikyo UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm Description

Outcomes

Primary Outcome Measures

Safety(toxicities as assessed by NCI CTCAE version3)

Secondary Outcome Measures

Peptide specific CTL induction

DTH to peptide

Changes in levels of regulatory T cells

Objective response rate as assessed by RECIST criteria

Time to progression

survival

Full Information

NCT ID

NCT00632333

First Posted

February 29, 2008

Last Updated

July 20, 2011

Sponsor

Teikyo University

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT00632333

Brief Title

Combination of Chemoradiation Therapy and Epitope Peptide Vaccine Therapy in Treating Patients With Esophageal Cancer

Official Title

Phase I Study of Chemoradiation Therapy With Epitope Peptide Vaccine Therapy in Treating Patients With Unresectable, Advanced or Recurrent Esophageal Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

September 2009

Overall Recruitment Status

Unknown status

Study Start Date

February 2008 (undefined)

Primary Completion Date

December 2011 (Anticipated)

Study Completion Date

March 2012 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor

Teikyo University

Collaborators

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

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Esophageal Cancer

Keywords

Epitope peptide, Vaccination, Chemoradiation, Esophageal cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

9 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

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

Other Intervention Name(s)

CDDP, 5-FU

Intervention Description

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.

Primary Outcome Measure Information:

Title

Safety(toxicities as assessed by NCI CTCAE version3)

Time Frame

3 months

Secondary Outcome Measure Information:

Title

Peptide specific CTL induction

Time Frame

3 months

Title

DTH to peptide

Time Frame

3 months

Title

Changes in levels of regulatory T cells

Time Frame

3 months

Title

Objective response rate as assessed by RECIST criteria

Time Frame

1 year

Title

Time to progression

Time Frame

1 year

Title

survival

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Hisae Iinuma, PhD

Phone

+81-33-964-1211

iinuma@med.teikyo-u.ac.jp

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kota Okinaga, MD, PhD

Organizational Affiliation

Teikyo University , Department Surgery

Official's Role

Study Chair

Facility Information:

Facility Name

Teikyo University

City

2-11-1 Kaga Itabashi-ku

State/Province

Tokyo

ZIP/Postal Code

173-0003

Country

Japan

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Hisae Iinuma, PhD

Phone

+81-33-964-1211

iinuma@med.teikyo-u.ac.jp

First Name & Middle Initial & Last Name & Degree

Hisae Iinuma, PhD

12. IPD Sharing Statement

Citations:

PubMed Identifier

15939316

Citation

Yildirim Z, Kotuk M, Iraz M, Kuku I, Ulu R, Armutcu F, Ozen S. Attenuation of bleomycin-induced lung fibrosis by oral sulfhydryl containing antioxidants in rats: erdosteine and N-acetylcysteine. Pulm Pharmacol Ther. 2005;18(5):367-73. doi: 10.1016/j.pupt.2005.02.001. Epub 2005 Mar 23.

Results Reference

background

PubMed Identifier

12070285

Citation

Li Y, Wang MN, Li H, King KD, Bassi R, Sun H, Santiago A, Hooper AT, Bohlen P, Hicklin DJ. Active immunization against the vascular endothelial growth factor receptor flk1 inhibits tumor angiogenesis and metastasis. J Exp Med. 2002 Jun 17;195(12):1575-84. doi: 10.1084/jem.20020072. Erratum In: J Exp Med 2002 Aug 19;196(4):557.

Results Reference

background

PubMed Identifier

12415261

Citation

Niethammer AG, Xiang R, Becker JC, Wodrich H, Pertl U, Karsten G, Eliceiri BP, Reisfeld RA. A DNA vaccine against VEGF receptor 2 prevents effective angiogenesis and inhibits tumor growth. Nat Med. 2002 Dec;8(12):1369-75. doi: 10.1038/nm1202-794. Epub 2002 Nov 4.

Results Reference

background

PubMed Identifier

8851721

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. doi: 10.1111/j.1399-0039.1996.tb02520.x.

Results Reference

background

PubMed Identifier

16002679

Citation

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. doi: 10.4049/jimmunol.175.2.820. Erratum In: J Immunol. 2005 Nov 1;175(9):6235. Prete, Salvatore [corrected to Prete, Salvatore Pasquale].

Results Reference

background

PubMed Identifier

12378509

Citation

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. doi: 10.1053/hupa.2002.126879.

Results Reference

background

PubMed Identifier

16630140

Citation

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. doi: 10.1111/j.1349-7006.2006.00194.x.

Results Reference

background

PubMed Identifier

16108831

Citation

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. doi: 10.1111/j.1349-7006.2005.00073.x.

Results Reference

background

PubMed Identifier

9500606

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. doi: 10.1038/nm0398-321.

Results Reference

background

PubMed Identifier

15591460

Citation

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. doi: 10.1093/jjco/hyh107. Erratum In: Jpn J Clin Oncol. 2005 Feb;35(2):108.

Results Reference

background

PubMed Identifier

12419749

Citation

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. doi: 10.1093/annonc/mdf301.

Results Reference

background

PubMed Identifier

9935203

Citation

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. doi: 10.1002/(sici)1097-0215(19990118)80:23.0.co;2-s.

Results Reference

background

PubMed Identifier

24708624

Citation

Iinuma H, Fukushima R, Inaba T, Tamura J, Inoue T, Ogawa E, Horikawa M, Ikeda Y, Matsutani N, Takeda K, Yoshida K, Tsunoda T, Ikeda T, Nakamura Y, Okinaga K. Phase I clinical study of multiple epitope peptide vaccine combined with chemoradiation therapy in esophageal cancer patients. J Transl Med. 2014 Apr 3;12:84. doi: 10.1186/1479-5876-12-84.

Results Reference

derived

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Combination of Chemoradiation Therapy and Epitope Peptide Vaccine Therapy in Treating Patients With Esophageal Cancer

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