Histocompatibility Leukocyte Antigen (HLA)-A*0201 Restricted Peptide Vaccine Therapy in Patients With Colorectal Cancer

Phase I/II Study of Multiple-Vaccine Therapy Using Epitope Peptide Restricted to HLA-A*0201 in Combination With Tegafur/Uracil/Folinate in Treating Patients With Refractory Colorectal Cancer

The purpose of this study is to evaluate the safety and time to progression of HLA-A*0201 restricted epitope peptides VEGFR1 and VEGFR2 emulsified with Montanide ISA 51 in combination with Tegafur/Uracil/Folinate chemotherapy.

VEGF receptor 1 and 2 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 vivo. According to these findings, in this trial, we evaluate the safety, clinical and immunological response of those peptides. Patients will be vaccinated twice a week for 8 weeks. On each vaccination day, VEGFR1 peptide (1mg) and VEGFR2 peptide (1mg) mixed with Montanide ISA 51 will be administered by subcutaneous injection. The patients will also receive oral chemotherapy (Tegafur/Uracil/Folinate) simultaneously. Repeated cycles of the vaccine and the chemotherapy will be administered until patients develop progressive disease or unacceptable toxicity, whichever occurs first. In the phase I study, we evaluate the safety and tolerability of these peptide vaccine. In the following phase II study, we evaluate the immunological and clinical response of this vaccine therapy.

Inclusion Criteria:

• Advanced or recurrent colorectal cancer

• Resistant against chemotherapy including CPT-11, l-OHP、+/- 5-FU +/- bevacizumab or difficult to continue the chemotherapy due to intolerable side effect(s)

• ECOG performance status 0-2

• Life expectancy > 3 months

• HLA-A*0201

• Laboratory values as follows

  • 2000/mm3<WBC<15000/mm3
  • Platelet count>100000/mm3
  • Bilirubin < 3.0mg/dl
  • Asparate transaminase < 150IU/L
  • Alanine transaminase < 150IU/L
  • Creatinine < 3.0mg/dl

• Able to receive oral Tegafur/Uracil/Folinate therapy

• 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
• Unhealed external wound
• Concurrent treatment with steroids or immunosuppressing agent
• Prior chemotherapy,radiation therapy, or immunotherapy within 4 weeks
• Uncontrolled brain and/or intraspinal lesion(s)
• History of allergy to Tegafur, Uracil, and/or Folinate
• Decision of unsuitableness by principal investigator or physician-in-charge