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

Primary Purpose

Colorectal Cancer, Colon Cancer, Rectal Cancer

Status

Terminated

Phase

Phase 1

Locations

Japan

Study Type

Interventional

Intervention

VEGFR1 and VEGFR2

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring HLA-A*0201, Peptide Vaccine, VEGFR1, VEGFR2

Eligibility Criteria

20 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

The Institute of Medical Science, The University of Tokyo

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm Description

Outcomes

Primary Outcome Measures

safety(Phase I:toxicities as assessed by NCI CTCAE version3) and efficacy(Phase II:Feasibility as evaluated by RECIST)

Secondary Outcome Measures

To evaluate immunological responses

Full Information

NCT ID

NCT00677612

First Posted

May 12, 2008

Last Updated

December 28, 2009

Sponsor

Tokyo University

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT00677612

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2009

Overall Recruitment Status

Terminated

Why Stopped

Lack of financial support

Study Start Date

May 2008 (undefined)

Primary Completion Date

March 2009 (Actual)

Study Completion Date

March 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Tokyo 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 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.

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.

6. Conditions and Keywords

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

Colorectal Cancer, Colon Cancer, Rectal Cancer

Keywords

HLA-A*0201, Peptide Vaccine, VEGFR1, VEGFR2

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

14 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

VEGFR1 and VEGFR2

Other Intervention Name(s)

UFT, UZEL

Intervention Description

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.

Primary Outcome Measure Information:

Title

safety(Phase I:toxicities as assessed by NCI CTCAE version3) and efficacy(Phase II:Feasibility as evaluated by RECIST)

Time Frame

2 months

Secondary Outcome Measure Information:

Title

To evaluate immunological responses

Time Frame

2 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Masaru Shinozaki, MD/PhD

Organizational Affiliation

Head, Department of Surgery

Official's Role

Principal Investigator

Facility Information:

Facility Name

The Institute of Medical Science, The University of Tokyo

City

Minato-ku

State/Province

Tokyo

ZIP/Postal Code

108-8639

Country

Japan

12. IPD Sharing Statement

Citations:

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

17020992

Citation

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. doi: 10.1158/1078-0432.CCR-06-0750.

Results Reference

background

PubMed Identifier

15930316

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. doi: 10.1158/0008-5472.CAN-04-3759.

Results Reference

background

Links:

URL

http://www.transrec.jp/

Description

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

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

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