Safety and Efficacy Study of Epitope Peptide To Treat HLA-A*24 or A*02-positive Advanced Solid Tumors

The purpose of this study is to evaluate the safety, tolerability, immune response and clinical efficacies of HLA-A*2402 or HLA-A*0201 restricted epitope peptides (VEGF-R1 and VEGF-R2) emulsified with Montanide ISA 51 for advanced solid tumors.

In this phase I/II trial, the investigators examine using a combination of the two peptides the safety, immunogenicity, and antitumor effect of vaccine treatment for HLA-A*2402 or HLA-A*0201-positive advanced solid tumor patients who are refractory to standard therapy.

• HLA-A*2402 or A*0201 restricted peptides (Biological): Open Label, Non-Randomized, Safety/Efficacy study: 1. HLA-A*2402-positive patients will be vaccinated subcutaneously once a week with HLA-A*2402 restricted peptides for VEGF-R1 and VEGF-R2 with adjuvant. 2. HLA-A*0201-positive patients will be vaccinated subcutaneously once a week with HLA-A*0201 restricted peptides for VEGF-R1 and VEGF-R2 with adjuvant.

Primary outcomes

• Evaluation of safety: the number of adverse events of vaccination therapy. [2 months]
• Evaluation of clinical efficacy: Overall survival. [2 months]

Secondary outcomes

• Various immunological responses including peptides specific CTL, antigen cascade, regulatory T cells, cancer antigens and HLA levels. [2 months]
• Evaluation of clinical efficacy: Progression free survival. [2 months]
• Evaluation of clinical efficacy: Tumor markers. [2 months]
• Evaluation of clinical efficacy: Objective response rate. [2 months]

Sex: All, ages: 20 Years to 85 Years

Inclusion Criteria:

1. Advanced solid tumors that are refractory to standard therapies or that cannot be treated with those due to medical reason.
2. ECOG performance status 0-1
3. Age between 20 to 85
4. Clinical efficacy can be evaluated by some methods
5. No prior chemotherapy, radiation therapy, hyperthermia or immunotherapy within two weeks
6. Life expectancy > 3 months
7. Laboratory values as follows 1500/mm3 < WBC < 10000/mm3 Platelet count > 75000/mm3 15% < Lymphcyte fraction Asparate transaminase < 3 X cutoff value Alanine transaminase < 3 X cutoff value Total bilirubin < 3 X cutoff value Serum creatinine < 2X cutoff value
8. HLA-A*2402 or HLA-A*0201
9. Able and willing to give valid written informed consent

Exclusion Criteria:

1. Active and uncontrolled cardiac disease (i.e. coronary syndromes, arrhythmia)
2. Myocardial infarction within six months before entry
3. Breastfeeding and Pregnancy (woman of child bearing potential)
4. Active and uncontrolled infectious disease
5. Concurrent treatment with steroids or immunosuppressing agent
6. Other malignancy requiring treatment
7. Non-cured traumatic wound
8. Decision of unsuitableness by principal investigator or physician-in-charge

• Yataro Daigo, MD, PhD, Principal investigator, Shiga University