PhaseⅠ/Ⅱ Study of URLC10-177 and TTK-567 Peptide Vaccine Combined With CpG7909 in Patients With Esophageal Cancer

PhaseⅠ/Ⅱ Study of URLC10-177 and TTK-567 Peptide Vaccine Combined With CpG7909 in Patients With Esophageal Cancer

Phase I/II Study of URLC10-177 and TTK-567, Novel Tumor Specific Epitope Peptides Restricted to HLA-A*2402 Derived From Tumor Associated Antigens, Combined With CpG7909, a TLR9 Agonist, in Patients With Advanced or Recurrent Esophageal Cancer.

This is a single institution phase I / II trial to evaluate the safety and efficacy of URLC10-177 and TTK-567 emulsified with Montanide ISA 51 in combination with different doses of CpG7909 in patients with advanced or recurrent esophageal cancer.

phase I: Patients will be vaccinated on day 1,8,15 and 22 of each 28-day treatment cycles. On each vaccination day, the URLC10-117 peptide(1mg) and TTK-567 peptide(1mg) mixed with CpG 7909 (escalating doses: 0, 0.02, 0.1mg/kg) emulsified with Montanide ISA 51 will be administered by subcutaneous injection. Repeated cycles of vaccine will be administered until patients develop progressive disease or unacceptable toxicity, or for maximum 2 cycles, whichever occurs first. In this phase I study, we evaluate the safety and tolerability of URLC10-177, TTK-567 and different doses of CpG7909 to determine the recommended phase II dose of CpG7909. phase II: Patients will be vaccinated on day 1,8,15 and 22 of each 28-day treatment cycles. On each vaccination day, the URLC10-117 peptide(1mg) and TTK-567 peptide(1mg) mixed with CpG 7909 (recommended dose determined in phase I study) emulsified with Montanide ISA 51 will be administered by subcutaneous injection. Repeated cycles of vaccine will be administered for 2 cycles. In this phase II study, we evaluate the efficacy of this vaccine therapy.

Safety(Phase I:toxicities as assessed by NCI CTCAE version3) and efficacy(Phase II:Feasibility as evaluated by RECIST)

Inclusion Criteria: DISEASE CHARACTERISTICS locally advanced or metastatic esophageal cancer precluding curative surgical resection and recurrent esophageal cancer measurable disease by CT scan PATIENT CHARACTERISTICS ECOG performance status 0-1 Life expectancy > 3 months Laboratory values as follows 2000/mm3 < WBC < 15000/mm3 Platelet count > 75000/mm3 Aspartate transaminase < 150 IU/L Alanine transaminase < 150 IU/L Creatinine < 2.0 mg/dl HLA-A*2402 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 Concurrent treatment with steroids or immunosuppressing agent Prior chemotherapy,radiation therapy, or immunotherapy within 4 weeks Clinically significant heart disease Decision of unsuitableness by principal investigator or physician-in-charge

Iwahashi M, Katsuda M, Nakamori M, Nakamura M, Naka T, Ojima T, Iida T, Yamaue H. Vaccination with peptides derived from cancer-testis antigens in combination with CpG-7909 elicits strong specific CD8+ T cell response in patients with metastatic esophageal squamous cell carcinoma. Cancer Sci. 2010 Dec;101(12):2510-7. doi: 10.1111/j.1349-7006.2010.01732.x. Epub 2010 Sep 28.