Clinical trial NCT00622622: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pancreatic Cancer
Lead sponsor: Wakayama Medical University
Sponsor class: OTHER
Collaborators: name: Human Genome Center, Institute of Medical Science, University of Tokyo
First posted: 2008-02-25
Enrollment: 21
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, 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.

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

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

Primary outcomes:
measure: Safety(toxicities as assessed by NCI CTCAE version 3)
timeFrame: 3 months
Secondary outcomes:
measure: VEGFR2 peptide specific CTL induction in vitro
timeFrame: 3 months
measure: DTH to VEGFR2 peptide
timeFrame: 3 months
measure: Changes in levels of regulatory T cells
timeFrame: 3 months
measure: Objective response rate as assessed by RECIST criteria
timeFrame: 1 year
measure: Time to progression
timeFrame: 1 years
measure: survival
timeFrame: 1 years
Other outcomes:
Locations:
city: 811-1 Kimiidera, Wakayama
country: Japan
facility: Wakayama Medical University Hospital
state: Wakayama
Study officials:
affiliation: Wakayama Medical University, Second Department of Surgery
name: Hiroki Yamaue, MD
role: STUDY_CHAIR
References:
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