Multiple-Vaccine Therapy in Treating Patients With Non-small Cell Lung Cancer

Phase I Study of Multiple-vaccine Therapy Including Antiangiogenic Vaccine Using Epitope Peptide Restricted to HLA-A*2402 in Treating Patients With Unresectable or Recurrent Non-small Cell Lung Cancer

The purpose of this study is to evaluate the safety, tolerability, immune response and clinical response of different doses of HLA-A*2402 restricted epitope peptides URLC10, TTK, VEGFR1 and VEGFR2 emulsified with Montanide ISA 51.

Study Overview

• Status: Completed
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Biological: HLA-A*2402restricted URLC10, TTK, VEGFR1 and VEGFR2

Detailed Description

URLC10 and TTK have been identified as cancer specific molecules especially in non small cell lung cancer using genome-wide expression profile analysis by cDNA microarray technique. We have determined the HLA-A*2402 restricted epitope peptides derived from these molecules. We also tend to use the peptides targeting to tumor angiogenesis. 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, immunological and clinical response of those peptides.

• Study Type: Interventional
• Enrollment (Anticipated): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fuskushima
    • Fukushima, Fuskushima, Japan, 960-1295
      • Fukushima Medical University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Disease characteristics

1. Advanced or recurrent non small cell lung cancer
2. Second line or later therapeutic status

Patient characteristics

1. ECOG performance status 0-2
2. Life expectancy > 3 months
3. HLA-A*2402
4. Laboratory values as follows 1500/mm3<WBC<15000/mm3 Platelet count>75000/mm3 Bilirubin < 3.0mg/dl Asparate transaminase < 99IU/L Alanine transaminase < 126IU/L Creatinine < 2.2mg/dl
5. Able and willing to give valid written informed consent

Exclusion Criteria:

1. Active and uncontrolled cardiac disease (includes patients with myocardial infarction within 6 months before entry)
2. Pregnancy (woman of child bearing potential)
3. Active and uncontrolled infectious disease
4. Adrenal cortical steroid hormone dependent status
5. Decision of unsuitableness by principal investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Biological: HLA-A*2402restricted URLC10, TTK, VEGFR1 and VEGFR2; Escalating doses of every peptide will be administered by subcutaneous injection on days 1,8,15 and 22 of each 28-day treatment cycles. Planned doses of peptides are 0.5mg, 1.0mg and 3.0mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Adverse effects, dose limiting toxicity, and maximum tolerated dose as measured by CTCAE ver3.0 pre treatment, during study treatment, and 3 months after treatment	3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in levels of regulatory T cells	3 months
Peptides specific CTL responses in vitro	3 months
Objective response rate as assessed using RECIST criteria	6 months

Collaborators and Investigators

• Sponsor: Fukushima Medical University
• Collaborators: Human Genome Center, Institute of Medical Science, University of Tokyo
• Investigators: Study Chair: Mitsukazu Gotoh, MD,PhD, Fukushima Medical University, First department of Surgery

Publications and helpful links

General Publications

• Ishizaki H, Tsunoda T, Wada S, Yamauchi M, Shibuya M, Tahara H. Inhibition of tumor growth with antiangiogenic cancer vaccine using epitope peptides derived from human vascular endothelial growth factor receptor 1. Clin Cancer Res. 2006 Oct 1;12(19):5841-9. doi: 10.1158/1078-0432.CCR-06-0750.
• Wada S, Tsunoda T, Baba T, Primus FJ, Kuwano H, Shibuya M, Tahara H. Rationale for antiangiogenic cancer therapy with vaccination using epitope peptides derived from human vascular endothelial growth factor receptor 2. Cancer Res. 2005 Jun 1;65(11):4939-46. doi: 10.1158/0008-5472.CAN-04-3759.
• Uchida N, Tsunoda T, Wada S, Furukawa Y, Nakamura Y, Tahara H. Ring finger protein 43 as a new target for cancer immunotherapy. Clin Cancer Res. 2004 Dec 15;10(24):8577-86. doi: 10.1158/1078-0432.CCR-04-0104.
• Suda T, Tsunoda T, Uchida N, Watanabe T, Hasegawa S, Satoh S, Ohgi S, Furukawa Y, Nakamura Y, Tahara H. Identification of secernin 1 as a novel immunotherapy target for gastric cancer using the expression profiles of cDNA microarray. Cancer Sci. 2006 May;97(5):411-9. doi: 10.1111/j.1349-7006.2006.00194.x.
• Watanabe T, Suda T, Tsunoda T, Uchida N, Ura K, Kato T, Hasegawa S, Satoh S, Ohgi S, Tahara H, Furukawa Y, Nakamura Y. Identification of immunoglobulin superfamily 11 (IGSF11) as a novel target for cancer immunotherapy of gastrointestinal and hepatocellular carcinomas. Cancer Sci. 2005 Aug;96(8):498-506. doi: 10.1111/j.1349-7006.2005.00073.x.
• Suzuki H, Fukuhara M, Yamaura T, Mutoh S, Okabe N, Yaginuma H, Hasegawa T, Yonechi A, Osugi J, Hoshino M, Kimura T, Higuchi M, Shio Y, Ise K, Takeda K, Gotoh M. Multiple therapeutic peptide vaccines consisting of combined novel cancer testis antigens and anti-angiogenic peptides for patients with non-small cell lung cancer. J Transl Med. 2013 Apr 11;11:97. doi: 10.1186/1479-5876-11-97.

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: February 20, 2008
• First Submitted That Met QC Criteria: March 3, 2008
• First Posted (Estimate): March 12, 2008

Study Record Updates

• Last Update Posted (Estimate): August 15, 2013
• Last Update Submitted That Met QC Criteria: August 13, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: FVT-L0701