Survivin Peptide Vaccination for Patients With Advanced Melanoma, Pancreatic, Colon and Cervical Cancer

Pancreatic Cancer Clinical Trial

Official title:

Vaccination of Patients With Advanced Melanoma, Pancreatic, Colon and Cervical Cancer With HLA-A1, -A2 and -B35 Restricted Survivin Peptides

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00108875
• Other study ID #: SuMo-Sec-01
• Secondary ID: PEI 0899/01IRB 0
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: April 19, 2005
• Last updated: July 27, 2006
• Start date: April 2003

Study information

• Verified date: June 2005
• Source: Julius-Maximilians University
• Contact: Juergen C Becker, MD, PhD
• Phone: +49-931-201-26396
• Email: becker_jc[@]klinik.uni-wuerzburg.de
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial Summary

This study evaluates the safety, the immunological response and the clinical outcome of a vaccination with survivin peptides for patients with advanced melanoma, pancreatic, colon and cervical carcinoma.

Description:

As prognosis of advanced melanoma, pancreatic, colon and cervical cancer remains gloomy, new therapeutic modalities have to be developed to improve the patient´s clinical outcome. Immunotherapy, which targets tumor associated antigens of tumor cells or tumor stroma, is currently an intensively investigated, novel therapeutic option. As survivin is expressed both by neoplastic cells as well as by endothelial cells of the tumor vasculature, this antigen is an intriguing target molecule. Spontaneous cytotoxic T-cell responses against different survivin epitopes in cancer patients underline the relevance of survivin-directed immunological trials. This study is comprised of a peptide vaccine with HLA-A1, -A2 and -B35 restricted survivin epitopes in Montanide ISA-51 for patients with stage IV melanoma, advanced pancreatic, colon and cervical carcinoma. The vaccine is applicated as a deep subcutaneous injection. Vaccination is administered for the first 2 months weekly, afterwards every 4 weeks. Standard staging examinations are performed every three months. Clinical, laboratory and immunological monitoring is done every month.Diagnostic leucapheresis is performed before first vaccination and afterwards every 2 months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years to 90 Years

Eligibility

Inclusion Criteria:

• Advanced melanoma, pancreatic, colon and cervical cancer

• At least 1 prior postoperative conventional therapy (chemotherapy, radiation, immunotherapy)

• HLA-A1, -A2, -B35

• More than 4 weeks since last chemo-, immune- or radiotherapy

• ECOG-PS (Eastern Cooperative Oncology Group- Performance Status) of 0-1

• Sufficient renal, hepatic and bone marrow function: thrombocytes > 75.000/ul; hb > 9 g/dl; leucocytes > 2.500/ul; creatinine < 2 mg/dl; GOT/GPT < twice the normal value

• negative for HIV and Hbs

• Older than 18 years

• Informed consent

Exclusion Criteria:

• Acute/chronic infections

• Positive for HIV, Hbs

• Autoimmune disorders

• Pregnancy, breast feeding

Study Design

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

Related Conditions & MeSH terms

• Cervical Cancer
• Colon Cancer
• Malignant Melanoma
• Melanoma
• Pancreatic Cancer
• Pancreatic Neoplasms
• Uterine Cervical Neoplasms

Intervention

Biological:
• Survivin peptide vaccine

Locations

Country	Name	City	State
Germany	Julius-Maximilians-University of Wuerzburg, Germany, Department of Dermatology	Wuerzburg	Bavaria

Sponsors (1)

Lead Sponsor	Collaborator
Julius-Maximilians University

Country where clinical trial is conducted

Germany, 

References & Publications (7)

Andersen MH, Pedersen LO, Becker JC, Straten PT. Identification of a cytotoxic T lymphocyte response to the apoptosis inhibitor protein survivin in cancer patients. Cancer Res. 2001 Feb 1;61(3):869-72. — View Citation

Andersen MH, Pedersen LO, Capeller B, Bröcker EB, Becker JC, thor Straten P. Spontaneous cytotoxic T-cell responses against survivin-derived MHC class I-restricted T-cell epitopes in situ as well as ex vivo in cancer patients. Cancer Res. 2001 Aug 15;61(16):5964-8. — View Citation

Blanc-Brude OP, Mesri M, Wall NR, Plescia J, Dohi T, Altieri DC. Therapeutic targeting of the survivin pathway in cancer: initiation of mitochondrial apoptosis and suppression of tumor-associated angiogenesis. Clin Cancer Res. 2003 Jul;9(7):2683-92. — View Citation

Kim HS, Shiraki K, Park SH. Expression of survivin in CIN and invasive squamous cell carcinoma of uterine cervix. Anticancer Res. 2002 Mar-Apr;22(2A):805-8. — View Citation

Otto K, Andersen MH, Eggert A, Keikavoussi P, Pedersen LØ, Rath JC, Böck M, Bröcker EB, Straten PT, Kämpgen E, Becker JC. Lack of toxicity of therapy-induced T cell responses against the universal tumour antigen survivin. Vaccine. 2005 Jan 4;23(7):884-9. — View Citation

Reker S, Becker JC, Svane IM, Ralfkiaer E, Straten PT, Andersen MH. HLA-B35-restricted immune responses against survivin in cancer patients. Int J Cancer. 2004 Mar 1;108(6):937-41. — View Citation

Reker S, Meier A, Holten-Andersen L, Svane IM, Becker JC, thor Straten P, Andersen MH. Identification of novel survivin-derived CTL epitopes. Cancer Biol Ther. 2004 Feb;3(2):173-9. Epub 2004 Feb 1. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival
Primary	Overall survival
Primary	Immunological response
Secondary	Best response