Clinical trial NCT00655785: Antiangiogenic Peptide Vaccine Therapy With Gemcitabine in Treating Patient With Pancreatic Cancer (Phase1/2)
Official title: Phase Ｉ/Ⅱ Sturdy on Antiangiogenic Vaccine Therapy Using Epitope Peptide Derived From VEGFR1 and VEGFR2 With Gemcitabine in Treating Patients With Unresectable, Recurrent, or Metastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pancreatic Cancer
Keywords: Epitope peptide
CTL
Pancreatic cancer
Vaccination VEGFR1
VEGFR2
Lead sponsor: Fukushima Medical University
Sponsor class: OTHER
Collaborators: name: Human Genome Center, Institute of Medical Science, University of Tokyo
First posted: 2008-04-10
Enrollment: 17
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, and tolerability of HLA-A\*2402 restricted epitope peptide VEGFR1 and VEGFR2 emulsified with Montanide ISA 51 in combination with gemcitabine

Detailed description: Vascular endothelial growth factor receptor 1 and 2 (VEGFR1 andVEGFR2) 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 in vivo. According to these findings, in this trial, we evaluate the safety, tolerability and immune response of these peptide emulsified with Montanide ISA 51 in combination with gemcitabine

Eligibility criteria: 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

PATIENTS CHARACTERISTICS

1. ECOG performance status 0-2
2. Life expectancy \> 3 months
3. Laboratory values as follows:

   * 2,000/mm3 \< WBC \< 15000/mm3
   * Platelet count ≥ 750,000/mm³
   * Total Bilirubin ≤ 1.5 x
   * 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 (women of childbearing potential: Refusal or inability to use effective means of contraception)
2. Breast-feeder
3. Active or uncontrolled infection
4. Prior chemotherapy, radiation therapy, or immunotherapy within 4 weeks
5. Serious or uncured wound
6. Active or uncontrolled other malignancy
7. Steroids or immunosuppressing agent dependent status
8. Interstitial pneumonia
9. Ileus
10. Decision of unsuitableness by principal investigator or physician-in-charge

Primary outcomes:
measure: toxicities as assessed by NCI-CACAE ver3)
timeFrame: 3 months
Secondary outcomes:
measure: Differences of peptide specific CTL response in vitro among sequence of gemcitabine and peptide vaccine administration
timeFrame: 3months
measure: CD8 population
timeFrame: 3months
measure: Change in level of regulatory T cells
timeFrame: 3months
measure: Objective response rate
timeFrame: 1year
measure: feasibility
timeFrame: 1year
measure: Survival
timeFrame: 1year
Other outcomes:
Locations:
city: Fukushima
country: Japan
facility: Fukushima Medical University Hospital
Study officials:
affiliation: Fukushima Medical University, Department
name: Mitsukazu Gotoh, M.D. & Ph.D
role: STUDY_CHAIR
References:
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.
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.
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.