Histocompatibility Leukocyte Antigen (HLA)-A*2402 Restricted Peptide Vaccine Therapy in Patients With Colorectal Cancer

Colorectal Cancer Clinical Trial

Official title:

Phase I/II Study of Multiple-Vaccine Therapy Using Epitope Peptide Restricted to HLA-A*2402 in Combination With Tegafur/Uracil/Folinate in Treating Patients With Refractory Colorectal Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00677287
• Other study ID #: CRC-A24-I, II
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: May 12, 2008
• Last updated: December 28, 2009
• Start date: May 2008
• Est. completion date: March 2009

Study information

• Verified date: May 2008
• Source: Tokyo University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and time to progression of HLA-A*2402 restricted epitope peptides RNF43, TOMM34, VEGFR1 and VEGFR2 emulsified with Montanide ISA 51 in combination with Tegafur/Uracil/Folinate chemotherapy.

Description:

RNF43 and TOMM34 have been identified as cancer specific molecules especially in colorectal cancer using genome-wide expression profile analysis by cDNA microarray technique. 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, immunological and clinical response of those peptides. Patients will be vaccinated twice a week for 8 weeks. On each vaccination day, RNF43 peptide (1mg), TOMM34 peptide (1mg), 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: March 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 85 Years

Eligibility

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*2402

• 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

Study Design

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

Related Conditions & MeSH terms

• Colon Cancer
• Colorectal Cancer
• Colorectal Neoplasms
• Rectal Cancer

Intervention

Biological:
• RNF43, TOMM34, VEGFR1 and VEGFR2
Patients will be vaccinated twice a week for 8 weeks. On each vaccination day, RNF43 peptide (1mg), TOMM34 peptide (1mg), 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.

Locations

Country	Name	City	State
Japan	The Institute of Medical Science, the University of Tokyo	Minato-ku	Tokyo

Sponsors (2)

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

Country where clinical trial is conducted

Japan, 

References & Publications (6)

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. — 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

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

Shimokawa T, Matsushima S, Tsunoda T, Tahara H, Nakamura Y, Furukawa Y. Identification of TOMM34, which shows elevated expression in the majority of human colon cancers, as a novel drug target. Int J Oncol. 2006 Aug;29(2):381-6. — View Citation

Uchida N, Tsunoda T, Wada S, Furukawa Y, Nakamura Y, Tahara H. Ring finger protein 43 as a new target for cancer immunotherapy. Clin Cancer Res. 2004 Dec 15;10(24):8577-86. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	safety(Phase I:toxicities as assessed by NCI CTCAE version3) and efficacy(Phase II:Feasibility as evaluated by RECIST)		2 months	Yes
Secondary	To evaluate immunological responses		2 months	No

External Links

•   Research Hospital, the Institute of Medical Science, the University of Tokyo