Novel Peptide Vaccination for Patients With Advanced Bladder Cancer

Bladder Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00635336
• Other study ID #: IMU-H18-59-P1
• Status: Completed
• Phase: Phase 1
• First received: March 5, 2008
• Last updated: October 20, 2010
• Start date: February 2007
• Est. completion date: February 2010

Study information

• Verified date: January 2009
• Source: Iwate Medical University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: February 2010
• Est. primary completion date: February 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 80 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Japan	Iwate Medical University School of Medicine	Morioka	Iwate

Sponsors (2)

Lead Sponsor	Collaborator
Iwate Medical University	Human Genome Center, Institute of Medical Science, University of Tokyo

Country where clinical trial is conducted

Japan, 

References & Publications (6)

Bienz M, Clevers H. Linking colorectal cancer to Wnt signaling. Cell. 2000 Oct 13;103(2):311-20. Review. — View Citation

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. — View 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. Epub 2007 Apr 23. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	feasibility (toxicities as assessed by NCI-CTCAE version 3)		3 years	Yes
Secondary	objective response rate as assessed by RECIST criteria		3 years	Yes
Secondary	CTL response		3 years	No
Secondary	CD8 population		3 years	No
Secondary	Change in level of regulatory T cells		3 years	No
Secondary	survival		3 years	Yes