Novel Peptide Vaccination for Patients With Advanced Bladder Cancer - Full Text View

Purpose

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

Condition	Intervention	Phase
Bladder Cancer	Biological: MPHOSPH1 and DEPDC1	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I Study of Vaccination With MPHOSHP1 and DEPDC1 Derived Epitope Peptides for HLA-A-24-positive Patients With Advanced Bladder Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: bladder cancer

MedlinePlus related topics: Bladder Cancer Cancer

U.S. FDA Resources

Further study details as provided by Iwate Medical University:

Primary Outcome Measures:

feasibility (toxicities as assessed by NCI-CTCAE version 3) [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

objective response rate as assessed by RECIST criteria [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
CTL response [ Time Frame: 3 years ] [ Designated as safety issue: No ]
CD8 population [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Change in level of regulatory T cells [ Time Frame: 3 years ] [ Designated as safety issue: No ]
survival [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	20
Study Start Date:	February 2007
Study Completion Date:	February 2010
Primary Completion Date:	February 2007 (Final data collection date for primary outcome measure)

Intervention Details:

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.

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

Ages Eligible for Study:	20 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00635336

Locations

Japan
Iwate Medical University School of Medicine
Morioka, Iwate, Japan, 020-8505

Sponsors and Collaborators

Iwate Medical University

Human Genome Center, Institute of Medical Science, University of Tokyo

Investigators

Study Chair:

Tomoaki Fujioka, M.D. & Ph.D.

Department of Urology, Iwate Medical University

More Information

Publications:

Kanehira M, Katagiri T, Shimo A, Takata R, Shuin T, Miki T, Fujioka T, Nakamura Y. Oncogenic role of MPHOSPH1, a cancer-testis antigen specific to human bladder cancer. Cancer Res. 2007 Apr 1;67(7):3276-85.

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. Epub 2007 Apr 23.

Rosenberg SA, Lotze MT, Yang JC, Aebersold PM, Linehan WM, Seipp CA, White DE. Experience with the use of high-dose interleukin-2 in the treatment of 652 cancer patients. Ann Surg. 1989 Oct;210(4):474-84; discussion 484-5.

Okabe H, Satoh S, Kato T, Kitahara O, Yanagawa R, Yamaoka Y, Tsunoda T, Furukawa Y, Nakamura Y. Genome-wide analysis of gene expression in human hepatocellular carcinomas using cDNA microarray: identification of genes involved in viral carcinogenesis and tumor progression. Cancer Res. 2001 Mar 1;61(5):2129-37.

Hasegawa S, Furukawa Y, Li M, Satoh S, Kato T, Watanabe T, Katagiri T, Tsunoda T, Yamaoka Y, Nakamura Y. Genome-wide analysis of gene expression in intestinal-type gastric cancers using a complementary DNA microarray representing 23,040 genes. Cancer Res. 2002 Dec 1;62(23):7012-7.

Bienz M, Clevers H. Linking colorectal cancer to Wnt signaling. Cell. 2000 Oct 13;103(2):311-20. Review. No abstract available.

Responsible Party:	Department of Urology, Iwate Medical University
ClinicalTrials.gov Identifier:	NCT00635336 History of Changes
Other Study ID Numbers:	IMU-H18-59-P1
Study First Received:	March 5, 2008
Last Updated:	October 20, 2010
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Keywords provided by Iwate Medical University:

Epitope peptide
CTL
Advanced bladder cancer
Vaccination
advanced bladder cancer which showed resistance for standard treatments

Additional relevant MeSH terms:

Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site

Neoplasms
Urinary Bladder Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on June 18, 2013