Clinical trial NCT00669292: PhaseⅠ/Ⅱ Study of URLC10-177 and TTK-567 Peptide Vaccine Combined With CpG7909 in Patients With Esophageal Cancer
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Esophageal Cancer
Keywords: esophageal cancer
peptide
URLC10
TTK
CpG7909
Lead sponsor: Wakayama Medical University
Sponsor class: OTHER
Collaborators: name: Human Genome Center, Institute of Medical Science, University of Tokyo
First posted: 2008-04-30
Enrollment: 29
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: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

DISEASE CHARACTERISTICS

1. locally advanced or metastatic esophageal cancer precluding curative surgical resection and recurrent esophageal cancer
2. measurable disease by CT scan

PATIENT CHARACTERISTICS

1. ECOG performance status 0-1
2. Life expectancy \> 3 months
3. 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
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,radiation therapy, or immunotherapy within 4 weeks
6. Clinically significant heart disease
7. Decision of unsuitableness by principal investigator or physician-in-charge

Primary outcomes:
measure: Safety(Phase I:toxicities as assessed by NCI CTCAE version3) and efficacy(Phase II:Feasibility as evaluated by RECIST)
timeFrame: 2 months
Secondary outcomes:
measure: To evaluate immunological responses (Phase I/II)
timeFrame: 2months
measure: To determine the recommended phase II dose of CpG7909(Phase I)
timeFrame: 2months
measure: To determine the clinical effectiveness in the patients with measurable disease(Phase I)
timeFrame: 2months
measure: To analyze the toxicity(Phase II)
timeFrame: 2months
measure: Time to progression(Phase II)
timeFrame: 5 years
measure: survival(Phase II)
timeFrame: 5 years
Other outcomes:
Locations:
city: 811-1 Kimiidera, Wakayama
country: Japan
facility: Wakayama Medical University Hospital
state: Wakayama
Study officials:
References:
citation: 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.