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

Esophageal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00632333
• Other study ID #: TPR07-079
• Status: Recruiting
• Phase: Phase 1
• First received: February 29, 2008
• Last updated: July 20, 2011
• Start date: February 2008
• Est. completion date: March 2012

Study information

• Verified date: September 2009
• Source: Teikyo University
• Contact: Hisae Iinuma, PhD
• Phone: +81-33-964-1211
• Email: iinuma[@]med.teikyo-u.ac.jp
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 9
• Est. completion date: March 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Patients must have unresectable, locally advanced, recurrent or metastatic disease of esophageal cancer.

2. measurable disease by CT scan

3. ECOG performance status of 0 to 2

4. Expected survival of at lease 3months

5. Patients must be HLA-A2402

6. 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

7. 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. Active or uncontrolled infection

4. Prior chemotherapy,radiation therapy or immunotherapy within 4 weeks

5. Concurrent treatment with steroid or immunosuppressing agent

6. Patient with peptic ulcer disease

7. Active or uncontrolled other malignancy

8. Other malignancy within 5 years prior to entry into the study, expect for treated non-melanoma skin cancer and cervical carcinoma in situ

9. Disease to the central nervous system

10. Decision of unsuitableness by principal investigator or physician-in-charge

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Japan	Teikyo University	2-11-1 Kaga Itabashi-ku	Tokyo

Sponsors (2)

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

Country where clinical trial is conducted

Japan, 

References & Publications (12)

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

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. — View 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. Erratum in: J Exp Med 2002 Aug 19;196(4):557. — 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

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. — View 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. Epub 2002 Nov 4. — 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, 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. — View 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. — View 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. — View 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. Epub 2005 Mar 23. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety(toxicities as assessed by NCI CTCAE version3)		3 months	Yes
Secondary	Peptide specific CTL induction		3 months	No
Secondary	DTH to peptide		3 months	No
Secondary	Changes in levels of regulatory T cells		3 months	No
Secondary	Objective response rate as assessed by RECIST criteria		1 year	No
Secondary	Time to progression		1 year	No
Secondary	survival		1 year	No