Gemcitabine With Antiangiogenic Peptide Vaccine Therapy in Patients With Pancreatic Cancer

NCT00622622 | Completed Phase 1 DMC

• 1 other identifier: WPR2-0710
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Safety(toxicities as assessed by NCI CTCAE version 3)

  3 months

Secondary Outcomes (6)

• VEGFR2 peptide specific CTL induction in vitro

  3 months

• DTH to VEGFR2 peptide

  3 months

• Changes in levels of regulatory T cells

  3 months

• Objective response rate as assessed by RECIST criteria

  1 year

• Time to progression

  1 years

Study Arms (1)

Phase I study

EXPERIMENTAL

Biological: VEGFR2-169 and gemcitabine

Interventions

VEGFR2-169 and gemcitabine BIOLOGICAL

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.

Phase I study

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• /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

You may not qualify if:

• 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

Sponsors & Collaborators

• Wakayama Medical University: lead
• Human Genome Center, Institute of Medical Science, University of Tokyo: collaborator

Study Sites (1)

Wakayama Medical University Hospital

811-1 Kimiidera, Wakayama, Wakayama, Japan

Location

Related Publications (7)

• 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.

  PMID: 15930316 BACKGROUND

• 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.

  PMID: 12070285 BACKGROUND

• 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.

  PMID: 12415261 BACKGROUND

• 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.

  PMID: 8851721 BACKGROUND

• 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.

  PMID: 16002679 BACKGROUND

• 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.

  PMID: 16000951 BACKGROUND

• 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.

  PMID: 19930156 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Hiroki Yamaue, MD

  Wakayama Medical University, Second Department of Surgery

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 13, 2008
• First Posted: February 25, 2008
• Study Start: November 1, 2006
• Primary Completion: December 1, 2006
• Study Completion: February 1, 2009
• Last Updated: February 18, 2009

Record last verified: 2009-02

Locations

JP (1)