Gemcitabine With Antiangiogenic Peptide Vaccine Therapy in Patients With Pancreatic Cancer

Pancreatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00622622
• Other study ID #: WPR2-0710
• Status: Completed
• Phase: Phase 1
• First received: February 13, 2008
• Last updated: February 17, 2009
• Start date: November 2006
• Est. completion date: February 2009

Study information

• Verified date: February 2009
• Source: Wakayama Medical University
• Contact: n/a
• 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, 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: February 2009
• Est. primary completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 80 Years

Eligibility

Inclusion Criteria:

DISEASE CHARACTERISTICS

1. locally advanced or metastatic pancreatic cancer precluding curative surgical resection and recurrent pancreatic cancer

2. measurable disease by CT scan

PATIENT CHARACTERISTICS

1. ECOG performance status 0-2

2. Life expectancy > 3 months

3. 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

4. HLA-A*2402

5. Able and willing to give valid written informed consent

Exclusion Criteria:

1. Pregnancy(woman of childbearing potential:Refusal or inability to use effective means of contraception)

2. Breastfeeding

3. Active or uncontrolled infection

4. Concurrent treatment with steroids or immunosuppressing agent

5. Prior chemotherapy of gemcitabine

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

7. Serious or nonhealing wound, ulcer, or bone fracture

8. Active or uncontrolled other malignancy

9. Ileus

10. Interstitial pneumonia

11. 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

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Biological:
• VEGFR2-169 and gemcitabine
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.

Locations

Country	Name	City	State
Japan	Wakayama Medical University Hospital	811-1 Kimiidera, Wakayama	Wakayama

Sponsors (2)

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

Country where clinical trial is conducted

Japan, 

References & Publications (6)

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

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. — 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

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(toxicities as assessed by NCI CTCAE version 3)		3 months	Yes
Secondary	VEGFR2 peptide specific CTL induction in vitro		3 months	No
Secondary	DTH to VEGFR2 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 years	No
Secondary	survival		1 years	No