Phase II randomised clinical trial of personalized peptide vaccination in combination with Dai-kenchu-to for colorectal cancer patients resistant to standard therapies

INTERVENTION: arm1: The right peptides (up to 4 peptides) for vaccination to individual patients will be selected in consideration of the pre‐existing host immunity assessed by the titers of anti‐peptide IgG before vaccination, and subcutaneously injected with incomplete Freund's adjuvant every week (3.0 mg/each peptide; 6 times/cycle). Dai‐kenchu‐to(5 g/time, 3 times/day) will be orally administered from the date of the first vaccination to the date of the sixth vaccination. If the patients want to continue the vaccination after completion of the first cycle of 6 vaccinations, the peptide vaccination will be allowed to continue (every 2‐4 weeks). arm2: The right peptides (up to 4 peptides) for vaccination to individual patients will be selected in consideration of the pre‐existing host immunity assessed by the titers of anti‐peptide IgG before vaccination, and subcutaneously injected with incomplete Freund's adjuvant every week (3.0 mg/each peptide; 6 times/cycle). If the patients want to continue the vaccination after completion of the first cycle of 6 vaccinations, the peptide vaccination will be allowed to continue (every 2‐4 weeks). CONDITION: colorectal cancer PRIMARY OUTCOME: Comparison of immune‐enhancing effects (changes in anti‐peptide IgG titers in plasma)between two groups. SECONDARY OUTCOME: 1.Comparison of peptide‐specific CTL responses in PBMCs between two groups.; 2. Comparison of safety between two groups.; 3. Comparison of overall survival between two groups . INCLUSION CRITERIA: The subjects must satisfy the following conditions. 1) Patients must be diagnosed as colorectal cancer resistant to standard therapies. Measurable lesions are not required. 2) Patients must be at a score level 0‐1 of ECOG performance status. 3) Patients must have IgGs reactive to at least two of the candidate peptides restricted to the patient's HLA types. 4)Patients must be expected to survive more than 3 months. 5) Patient's laboratory data must satisfy the followings: WBC is more than 2,500/mm3 Lymphocyte is more than 1,000/mm3 Hb is more than 8.0g/dl Platelet is more than 50,000/mm3 Serum Creatinine is less than 2.0mg/dl AST(GOT),ALT(GPT),ALP,gGTP, and total bilirubin are less than 2 times the ULN. 6) Patients must be more 20 year‐old. 7) Written informed consent must be obtained from patients. 8) Patients must be positive for HLA‐A2, A24, A26, A3, A11, A31 or A33.