Clinical trial NCT00674258: Histocompatibility Leukocyte Antigen (HLA)-A*2402 Restricted Peptide Vaccine Therapy in Patients With Non-Small Cell Lung Cancer
Official title: Phase I/II Study of Multiple-Vaccine Therapy Using Epitope Peptide Restricted to HLA-A*0201 in Treating Patients With Refractory Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Non Small Cell Lung Cancer
Keywords: HLA-A*2402
Peptide Vaccine
URLC10
TTK
KOC1
Lead sponsor: Tokyo University
Sponsor class: OTHER
Collaborators: name: Human Genome Center, Institute of Medical Science, University of Tokyo
First posted: 2008-05-07
Enrollment: 14
Sex: ALL
Minimum age (years): 20
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and time to progression of HLA-A\*2402 restricted epitope peptides URLC10, TTK and KOC1 emulsified with Montanide ISA 51.

Detailed description: URLC10,TTK and KOC1 has 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 and identified that these peptides 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. Patients will be vaccinated twice a week for 8 weeks. On each vaccination day, the URLC10-177 peptide(1mg), TTK-567 peptide(1mg) and KOC1-508 peptide(1mg) mixed 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, whichever occurs first. In the phase I study, we evaluate the safety and tolerability of these peptide vaccine. In the following phase II study, we evaluate the immunological and clinical response of this vaccine therapy.

Eligibility criteria: Inclusion Criteria:

Disease characteristics

* Advanced or recurrent non small cell lung cancer
* Second line or later therapeutic status Patient characteristics
* ECOG performance status 0-2
* Life expectancy \> 3 months
* HLA-A\*2402
* Laboratory values as follows

  * 2000/mm3\<WBC\<15000/mm3
  * Platelet count\>100000/mm3
  * Bilirubin \< 3.0mg/dl
  * Asparate transaminase \< 150IU/L
  * Alanine transaminase \< 150IU/L
  * Creatinine \< 3.0mg/dl
* 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
* Uncontrolled brain and/or intraspinal metastasis
* 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: two months
Secondary outcomes:
measure: To evaluate immunological responses
timeFrame: two months
Other outcomes:
Locations:
city: Tokyo
country: Japan
facility: The Institute of Medical Science, The University of Tokyo
Study officials:
affiliation: Tokyo University
name: Naohide Yamashita, MD/PhD
role: STUDY_CHAIR
References:
citation: Suda T, Tsunoda T, Daigo Y, Nakamura Y, Tahara H. Identification of human leukocyte antigen-A24-restricted epitope peptides derived from gene products upregulated in lung and esophageal cancers as novel targets for immunotherapy. Cancer Sci. 2007 Nov;98(11):1803-8. doi: 10.1111/j.1349-7006.2007.00603.x.
citation: Daigo Y, Nakamura Y. From cancer genomics to thoracic oncology: discovery of new biomarkers and therapeutic targets for lung and esophageal carcinoma. Gen Thorac Cardiovasc Surg. 2008 Feb;56(2):43-53. doi: 10.1007/s11748-007-0211-x. Epub 2008 Feb 24.
citation: 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.
citation: Rosenberg SA, Yang JC, Schwartzentruber DJ, Hwu P, Marincola FM, Topalian SL, Restifo NP, Dudley ME, Schwarz SL, Spiess PJ, Wunderlich JR, Parkhurst MR, Kawakami Y, Seipp CA, Einhorn JH, White DE. Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nat Med. 1998 Mar;4(3):321-7. doi: 10.1038/nm0398-321.
citation: 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.