Bladder Cancer
Conditions
Keywords
Epitope peptide, CTL, Advanced bladder cancer, Vaccination, advanced bladder cancer which showed resistance for standard treatments
Brief summary
The purpose of this study is to evaluate the safety and clinical efficacy of novel vaccination for advanced bladder cancer.
Detailed description
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.
Interventions
BIOLOGICALMPHOSPH1 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.
Sponsors
Human Genome Center, Institute of Medical Science, University of Tokyo
Iwate Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS 1. advanced bladder cancer which already showed resistance to standard treatments 2. Protein expression of MPHOSPH1 and DEPDC1 on the tumor PATIENTS CHARACTERISTICS 1. Patients who showed resistance to standard chemotherapies or radiotherapy 2. Histological diagnosis is transitional cell carcinoma 3. HLA-A\*2402 4. ECOG performance status of 0 to 1 5. Age ≥ 20 years, ≤80 years 6. 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 7. lesion of bladder cancer must express MPHOSPH1 or DEPDC1 8. Able and willing to give valid written informed consent
Exclusion criteria
1. Pregnancy (women of childbearing potential: Refusal or inability to use effective means of contraception) 2. Breastfeeding 3. Patients willing to childbearing ( Refusal or inability to use effective means of contraception) 4. Serious infections requiring antibiotics 5. Concomitant treatment with steroids or immunosuppressing agent 6. Other malignancy difficult to control. 7. Decision of unsuitableness by principal investigator or physician-in-charge
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| feasibility (toxicities as assessed by NCI-CTCAE version 3) | 3 years |
Secondary
| Measure | 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 |
Countries
Japan
Outcome results
None listed