Clinical trial NCT00635336: Novel Peptide Vaccination for Patients With Advanced Bladder Cancer
Official title: Phase I Study of Vaccination With MPHOSHP1 and DEPDC1 Derived Epitope Peptides for HLA-A-24-positive Patients With Advanced Bladder Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bladder Cancer
Keywords: Epitope peptide
CTL
Advanced bladder cancer
Vaccination
advanced bladder cancer which showed resistance for standard treatments
Lead sponsor: Iwate Medical University
Sponsor class: OTHER
Collaborators: name: Human Genome Center, Institute of Medical Science, University of Tokyo
First posted: 2008-03-13
Enrollment: 20
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
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 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.

Eligibility criteria: 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

Primary outcomes:
measure: feasibility (toxicities as assessed by NCI-CTCAE version 3)
timeFrame: 3 years
Secondary outcomes:
measure: objective response rate as assessed by RECIST criteria
timeFrame: 3 years
measure: CTL response
timeFrame: 3 years
measure: CD8 population
timeFrame: 3 years
measure: Change in level of regulatory T cells
timeFrame: 3 years
measure: survival
timeFrame: 3 years
Other outcomes:
Locations:
city: Morioka
country: Japan
facility: Iwate Medical University School of Medicine
state: Iwate
Study officials:
affiliation: Department of Urology, Iwate Medical University
name: Tomoaki Fujioka, M.D. & Ph.D.
role: STUDY_CHAIR
References:
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citation: Kanehira M, Harada Y, Takata R, Shuin T, Miki T, Fujioka T, Nakamura Y, Katagiri T. Involvement of upregulation of DEPDC1 (DEP domain containing 1) in bladder carcinogenesis. Oncogene. 2007 Sep 27;26(44):6448-55. doi: 10.1038/sj.onc.1210466. Epub 2007 Apr 23.