Safety Study of Peptide Cancer Vaccine To Treat HLA-A*02-positive Advanced Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, immune response and clinical efficacies of HLA-A*0201 or HLA-A*0206 restricted epitope peptides URLC10 emulsified with Montanide ISA 51 for advanced non-small cell lung cancers.

Detailed Description
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The investigators previously identified three novel HLA-A*0201 or HLA-A*0206-restricted epitope peptides, which were derived from a cancer-testis antigen, URLC10, as targets for cancer vaccination against lung cancer. In this phase I trial, the investigators examine using a combination of these three peptides the safety, immunogenicity, and antitumor effect of vaccine treatment for HHLA-A*0201 or HLA-A*0206-positive advanced non-small cell lung cancer patients who failed to standard therapy.

Official Title
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Phase I Study of Cancer Vaccine Therapy Using Epitope Peptide Restricted to HLA-A*02 (URLC10) in Patients With Non-small Cell Lung Cancer Refractory to Standard Therapy

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Biological: HLA-A*0201 or HLA-A*0206-restricted URLC10 peptides


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: NSCLC that can not undergo curative surgery and treatment, and is refractory to standard chemotherapy and radiotherapy ECOG performance status 0-2 Age between 20 to 85 Clinical efficacy can be evaluated by some methods No prior chemotherapy, radiation therapy, hyperthermia or immunotherapy within 4 weeks Life expectancy > 3 months Laboratory values as follows 1500/mm3 < WBC < 15000/mm3 Platelet count > 75000/mm3 Asparate transaminase < 3 X cutoff value Alanine transaminase < 3 X cutoff value Total bilirubin < 3 X cutoff value Serum creatinine < 2X cutoff value HLA-A*0201 or HLA-A*0206 Able and willing to give valid written informed consent Exclusion Criteria: Active and uncontrolled cardiac disease (i.e. coronary syndromes, arrhythmia) Myocardial infarction within six months before entry Breastfeeding and Pregnancy (woman of child bearing potential) Active and uncontrolled infectious disease Concurrent treatment with steroids or immunosuppressing agent Other malignancy requiring treatment Non-cured traumatic wound Decision of unsuitableness by principal investigator or physician-in-charge

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: URLC10-1mg<br>Patients will be vaccinated once a week for four weeks of a treatment cycle. On each vaccination day, the HLA-A*0201 or HLA-A*0206-restricted URLC10 peptide (1mg) mixed with Montanide ISA 51 will be administered by subcutaneous injection. | Biological: HLA-A*0201 or HLA-A*0206-restricted URLC10 peptides<br>* Escalating doses of every peptide will be administered by subcutaneous injection on days 1, 8, 15 and 22 of each treatment cycle. Planned doses of peptides are 1.0mg, 2.0mg and 3.0mg.<br>* Other names: URLC10;|
| Experimental: URLC10-2mg<br>Patients will be vaccinated once a week for four weeks of a treatment cycle. On each vaccination day, the HLA-A*0201 or HLA-A*0206-restricted URLC10 peptide (2mg) mixed with Montanide ISA 51 will be administered by subcutaneous injection. | Biological: HLA-A*0201 or HLA-A*0206-restricted URLC10 peptides<br>* Escalating doses of every peptide will be administered by subcutaneous injection on days 1, 8, 15 and 22 of each treatment cycle. Planned doses of peptides are 1.0mg, 2.0mg and 3.0mg.<br>* Other names: URLC10;|
| Experimental: URLC10-3mg<br>Patients will be vaccinated once a week for four weeks of a treatment cycle. On each vaccination day, the HLA-A*0201 or HLA-A*0206-restricted URLC10 peptide (3mg) mixed with Montanide ISA 51 will be administered by subcutaneous injection. | Biological: HLA-A*0201 or HLA-A*0206-restricted URLC10 peptides<br>* Escalating doses of every peptide will be administered by subcutaneous injection on days 1, 8, 15 and 22 of each treatment cycle. Planned doses of peptides are 1.0mg, 2.0mg and 3.0mg.<br>* Other names: URLC10;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of safety (NCI CTCAE version3): the number of adverse events of vaccination therapy. |  | 2 months | 
| Evaluation of tolerability (maximum tolerated dose, MTD and dose limiting toxicity, DLT) for the determination of the recommended dose for next phase trial. |  | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunological responses: Peptides specific CTL, Antigen cascade, Regulatory T cells, Cancer antigens and HLA levels. |  | 2 months (every time point(s) at which each course is completed) | 
| Evaluation of clinical efficacy: Objective response rate (RECIST1.1), Tumor markers, Overall survival, Progression free survival. |  | 2 months (every time point(s) at which each course is completed) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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URLC10, lung cancer, vaccine, HLA-A*0201, HLA-A*0206