Histocompatibility Leukocyte Antigen (HLA)-A*0201 Restricted Peptide Vaccine Therapy in Patients With Colorectal Cancer - Full Text View

Sponsors and Collaborators:	Tokyo University Human Genome Center, Institute of Medical Science, University of Tokyo
Information provided by:	Tokyo University
ClinicalTrials.gov Identifier:	NCT00677612

Purpose

The purpose of this study is to evaluate the safety and time to progression of HLA-A*0201 restricted epitope peptides VEGFR1 and VEGFR2 emulsified with Montanide ISA 51 in combination with Tegafur/Uracil/Folinate chemotherapy.

Condition	Intervention	Phase
Colorectal Cancer Colon Cancer Rectal Cancer	Biological: VEGFR1 and VEGFR2	Phase I Phase II

MedlinePlus related topics: Cancer Colorectal Cancer

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Phase I/II Study of Multiple-Vaccine Therapy Using Epitope Peptide Restricted to HLA-A*0201 in Combination With Tegafur/Uracil/Folinate in Treating Patients With Refractory Colorectal Cancer

Further study details as provided by Tokyo University:

Primary Outcome Measures:

safety(Phase I:toxicities as assessed by NCI CTCAE version3) and efficacy(Phase II:Feasibility as evaluated by RECIST) [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To evaluate immunological responses [ Time Frame: 2 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	14
Study Start Date:	May 2008
Estimated Study Completion Date:	April 2009
Estimated Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental	Biological: VEGFR1 and VEGFR2 Patients will be vaccinated twice a week for 8 weeks. On each vaccination day, VEGFR1 peptide (1mg) and VEGFR2 peptide (1mg) mixed with Montanide ISA 51 will be administered by subcutaneous injection in combination with Tegafur/Uracil/Folinate chemotherapy.

Detailed Description:

VEGF receptor 1 and 2 are essential targets to tumor angiogenesis, and we identified that peptides derived from these receptors significantly induce the effective tumor specific CTL response in vitro and vivo. According to these findings, in this trial, we evaluate the safety, clinical and immunological response of those peptides. Patients will be vaccinated twice a week for 8 weeks. On each vaccination day, VEGFR1 peptide (1mg) and VEGFR2 peptide (1mg) mixed with Montanide ISA 51 will be administered by subcutaneous injection. The patients will also receive oral chemotherapy (Tegafur/Uracil/Folinate) simultaneously. Repeated cycles of the vaccine and the chemotherapy will be administered until patients develop progressive disease or unacceptable toxicity, whichever occurs first. In the phase I study, we evaluate the safety and tolerability of these peptide vaccine. In the following phase II study, we evaluate the immunological and clinical response of this vaccine therapy.

Eligibility

Ages Eligible for Study:	20 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Advanced or recurrent colorectal cancer
Resistant against chemotherapy including CPT-11, l-OHP、+/- 5-FU +/- bevacizumab or difficult to continue the chemotherapy due to intolerable side effect(s)
ECOG performance status 0-2
Life expectancy > 3 months
HLA-A*0201
Laboratory values as follows
- 2000/mm3<WBC<15000/mm3
- Platelet count>100000/mm3
- Bilirubin < 3.0mg/dl
- Asparate transaminase < 150IU/L
- Alanine transaminase < 150IU/L
- Creatinine < 3.0mg/dl
Able to receive oral Tegafur/Uracil/Folinate therapy
Able and willing to give valid written informed consent

Exclusion Criteria:

Pregnancy(woman of childbearing potential:Refusal or inability to use effective means of contraception)
Breastfeeding
Active or uncontrolled infection
Unhealed external wound
Concurrent treatment with steroids or immunosuppressing agent
Prior chemotherapy,radiation therapy, or immunotherapy within 4 weeks
Uncontrolled brain and/or intraspinal lesion(s)
History of allergy to Tegafur, Uracil, and/or Folinate
Decision of unsuitableness by principal investigator or physician-in-charge

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00677612

Locations

Japan, Tokyo
The Institute of Medical Science, The University of Tokyo
Minato-ku, Tokyo, Japan, 108-8639

Sponsors and Collaborators

Tokyo University

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

Investigators

Principal Investigator:

Masaru Shinozaki, MD/PhD

Head, Department of Surgery

More Information

Additional Information:

Research Hospital, the Institute of Medical Science, the University of Tokyo This link exits the ClinicalTrials.gov site

Publications:

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.

Ishizaki H, Tsunoda T, Wada S, Yamauchi M, Shibuya M, Tahara H. Inhibition of tumor growth with antiangiogenic cancer vaccine using epitope peptides derived from human vascular endothelial growth factor receptor 1. Clin Cancer Res. 2006 Oct 1;12(19):5841-9.

Wada S, Tsunoda T, Baba T, Primus FJ, Kuwano H, Shibuya M, Tahara H. Rationale for antiangiogenic cancer therapy with vaccination using epitope peptides derived from human vascular endothelial growth factor receptor 2. Cancer Res. 2005 Jun 1;65(11):4939-46.

Responsible Party:	The Institute of Medical Science, The University of Tokyo ( Department of Surgery )
Study ID Numbers:	CRC-A02-I, II
Study First Received:	May 12, 2008
Last Updated:	January 5, 2009
ClinicalTrials.gov Identifier:	NCT00677612 History of Changes
Health Authority:	Japan: Institutional Review Board

Keywords provided by Tokyo University:

HLA-A*0201
Peptide Vaccine
VEGFR1
VEGFR2

Study placed in the following topic categories:

Digestive System Neoplasms
Tegafur
Rectal Neoplasms
Gastrointestinal Diseases
Colonic Diseases
Rectal Neoplasm
Intestinal Diseases

Rectal Diseases
Intestinal Neoplasms
Digestive System Diseases
Rectal Cancer
Gastrointestinal Neoplasms
Colonic Neoplasms
Colorectal Neoplasms

Additional relevant MeSH terms:

Digestive System Neoplasms
Rectal Neoplasms
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Intestinal Neoplasms

Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Neoplasms
Colonic Neoplasms
Colorectal Neoplasms

ClinicalTrials.gov processed this record on May 07, 2009