Novel Peptide Vaccination for Patients With Advanced Bladder Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and clinical efficacy of novel vaccination for advanced bladder cancer.

Detailed Description
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DEP domain containing 1(DEPDC1) and M phase phosphoprotein 1(MPHOSPH1) have been identified using genome-wide expression profile analysis by the use of cDNA microarray in our previous studies. We have determined the HLA-A*2402 restricted epitope peptides derived from DEPDC1, DEPDC1-9-294, and MPHOSPH1, MPHOSPH1-9-278. These epitopes showed strong IFN-g production when stimulated with the appropriate targets expressed the appropriate protein and HLA-A*2402. Furthermore, when vaccinated these peptides, specific CTLs were determined after the vaccination. Therefore we focused on the safety and efficacy of novel vaccination for the advanced bladder cancer patients who already showed resistance to standard chemotherapies or radiotherapy.

Official Title
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Phase I Study of Vaccination With MPHOSHP1 and DEPDC1 Derived Epitope Peptides for HLA-A-24-positive Patients With Advanced Bladder Cancer

Conditions
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Bladder Cancer

Intervention / Treatment
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* Biological: MPHOSPH1 and DEPDC1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DISEASE CHARACTERISTICS advanced bladder cancer which already showed resistance to standard treatments Protein expression of MPHOSPH1 and DEPDC1 on the tumor PATIENTS CHARACTERISTICS Patients who showed resistance to standard chemotherapies or radiotherapy Histological diagnosis is transitional cell carcinoma HLA-A*2402 ECOG performance status of 0 to 1 Age ≥ 20 years, ≤80 years WBC≥ 2,000/mm³, ≤15000/mm³ Platelet count ≥ 75000/mm³ AST, ALT ≤150 IU/l Total bilirubin ≤ 3.0 mg/dl Creatinine ≤ 3.0 mg/dl lesion of bladder cancer must express MPHOSPH1 or DEPDC1 Able and willing to give valid written informed consent Exclusion Criteria: Pregnancy (women of childbearing potential: Refusal or inability to use effective means of contraception) Breastfeeding Patients willing to childbearing ( Refusal or inability to use effective means of contraception) Serious infections requiring antibiotics Concomitant treatment with steroids or immunosuppressing agent Other malignancy difficult to control. Decision of unsuitableness by principal investigator or physician-in-charge

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: MPHOSPH1 and DEPDC1|DEPDC1-9-294, and/or MPHOSPH1-9-278 will be administered by subcutaneously injection once every week for 3 months thereafter once two weeks. These peptides are determined to administer in accordance with the protein expression using immunohistochemical staining. These peptides are conjugated with Montanide ISA 51 as an adjuvant.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| feasibility (toxicities as assessed by NCI-CTCAE version 3) |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate as assessed by RECIST criteria |  | 3 years | 
| CTL response |  | 3 years | 
| CD8 population |  | 3 years | 
| Change in level of regulatory T cells |  | 3 years | 
| survival |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epitope peptide, CTL, Advanced bladder cancer, Vaccination, advanced bladder cancer which showed resistance for standard treatments