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Gemcitabine With Antiangiogenic Peptide Vaccine Therapy in Patients With Pancreatic Cancer

Primary Purpose

Pancreatic Cancer

Status

Completed

Phase

Phase 1

Locations

Japan

Study Type

Interventional

Intervention

VEGFR2-169 and gemcitabine

About this trial

This is an interventional treatment trial for Pancreatic Cancer

Eligibility Criteria

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

Inclusion Criteria:

DISEASE CHARACTERISTICS

locally advanced or metastatic pancreatic cancer precluding curative surgical resection and recurrent pancreatic cancer
measurable disease by CT scan

PATIENT CHARACTERISTICS

ECOG performance status 0-2
Life expectancy > 3 months
Laboratory values as follows
- 2000/mm3 < WBC < 15000/mm3
- Platelet count > 75000/mm3
- Bilirubin < 3.0 mg/dl
- Aspartate transaminase < 150 IU/L
- Alanine transaminase < 150 IU/L
- Creatinine < 3.0 mg/dl
HLA-A*2402
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
Concurrent treatment with steroids or immunosuppressing agent
Prior chemotherapy of gemcitabine
Prior chemotherapy,radiation therapy, or immunotherapy within 4 weeks
Serious or nonhealing wound, ulcer, or bone fracture
Active or uncontrolled other malignancy
Ileus
Interstitial pneumonia
Decision of unsuitableness by principal investigator or physician-in-charge

Sites / Locations

Wakayama Medical University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Phase I study

Arm Description

Outcomes

Primary Outcome Measures

Safety(toxicities as assessed by NCI CTCAE version 3)

Secondary Outcome Measures

VEGFR2 peptide specific CTL induction in vitro

DTH to VEGFR2 peptide

Changes in levels of regulatory T cells

Objective response rate as assessed by RECIST criteria

Time to progression

survival

Full Information

NCT ID

NCT00622622

First Posted

February 13, 2008

Last Updated

February 17, 2009

Sponsor

Wakayama Medical University

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT00622622

Brief Title

Gemcitabine With Antiangiogenic Peptide Vaccine Therapy in Patients With Pancreatic Cancer

Official Title

Phase I Study of Gemcitabine With Antiangiogenic Vaccine Therapy Using Epitope Peptide Restricted to HLA-A*2402 Derived From VEGFR2 in Patients With Unresectable, Locally Advanced, Recurrent or Metastatic Pancreatic Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

February 2009

Overall Recruitment Status

Completed

Study Start Date

November 2006 (undefined)

Primary Completion Date

December 2006 (Actual)

Study Completion Date

February 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Wakayama Medical 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, tolerability and immune response of different doses of VEGFR2-169 emulsified with Montanide ISA 51 in combination with gemcitabine and to determine the recommended phase II dose.

Detailed Description

Vascular endothelial growth factor receptor 2(VEGFR2) is essential target for tumor angiogenesis, and VEGFR2-169 induces specific Cytotoxic T lymphocytes (CTL) against VEGFR2 expressed targets. VEGFR2-169 shows strong anti-tumor effects restricted to HLA-A*2402 in vitro, and this peptide induces CTL from cancer patients. 60% in Japanese population have HLA-A*2402. VEGFR2-169 is suitable for clinical trial, and gemcitabine has been approved against pancreatic cancer. Gemcitabine is reported to improve immune-response, therefore synergistic effect between vaccine therapy and chemotherapy will be expected. In this clinical trial, we evaluate the safety, tolerability and immune response of different doses of VEGFR2-169 emulsified with Montanide ISA 51 in combination with gemcitabine and to determine the recommended phase II dose of peptide.

6. Conditions and Keywords

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

Pancreatic 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

21 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Phase I study

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

VEGFR2-169 and gemcitabine

Intervention Description

Escalating doses of VEGFR2-169 will be administered by subcutaneous injection on days 1,8,15 and 22 of each 28-day treatment cycles(doses of 0.5,1.0,2.0mg/body are planned). Gemcitabine will be administered intravenously at a fixed dose of 1000mg/m2 on days 1,8 and 15. Repeated cycles of VEGFR2-169 and gemcitabine will be administered until patients develop progressive disease or unacceptable toxicity,or for maximum 2 cycles, whichever occurs first.

Primary Outcome Measure Information:

Title

Safety(toxicities as assessed by NCI CTCAE version 3)

Time Frame

3 months

Secondary Outcome Measure Information:

Title

VEGFR2 peptide specific CTL induction in vitro

Time Frame

3 months

Title

DTH to VEGFR2 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 years

Title

survival

Time Frame

1 years

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: DISEASE CHARACTERISTICS locally advanced or metastatic pancreatic cancer precluding curative surgical resection and recurrent pancreatic cancer measurable disease by CT scan PATIENT CHARACTERISTICS ECOG performance status 0-2 Life expectancy > 3 months Laboratory values as follows 2000/mm3 < WBC < 15000/mm3 Platelet count > 75000/mm3 Bilirubin < 3.0 mg/dl Aspartate transaminase < 150 IU/L Alanine transaminase < 150 IU/L Creatinine < 3.0 mg/dl HLA-A*2402 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 Concurrent treatment with steroids or immunosuppressing agent Prior chemotherapy of gemcitabine Prior chemotherapy,radiation therapy, or immunotherapy within 4 weeks Serious or nonhealing wound, ulcer, or bone fracture Active or uncontrolled other malignancy Ileus Interstitial pneumonia Decision of unsuitableness by principal investigator or physician-in-charge

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hiroki Yamaue, MD

Organizational Affiliation

Wakayama Medical University, Second Department of Surgery

Official's Role

Study Chair

Facility Information:

Facility Name

Wakayama Medical University Hospital

City

811-1 Kimiidera, Wakayama

State/Province

Wakayama

Country

Japan

12. IPD Sharing Statement

Citations:

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

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

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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

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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

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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

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PubMed Identifier

16000951

Citation

Dauer M, Herten J, Bauer C, Renner F, Schad K, Schnurr M, Endres S, Eigler A. Chemosensitization of pancreatic carcinoma cells to enhance T cell-mediated cytotoxicity induced by tumor lysate-pulsed dendritic cells. J Immunother. 2005 Jul-Aug;28(4):332-42. doi: 10.1097/01.cji.0000164038.41104.f5.

Results Reference

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PubMed Identifier

19930156

Citation

Miyazawa M, Ohsawa R, Tsunoda T, Hirono S, Kawai M, Tani M, Nakamura Y, Yamaue H. Phase I clinical trial using peptide vaccine for human vascular endothelial growth factor receptor 2 in combination with gemcitabine for patients with advanced pancreatic cancer. Cancer Sci. 2010 Feb;101(2):433-9. doi: 10.1111/j.1349-7006.2009.01416.x. Epub 2009 Oct 27.

Results Reference

derived

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Gemcitabine With Antiangiogenic Peptide Vaccine Therapy in Patients With Pancreatic Cancer

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