Immunotherapy of Recurrent Cervical Cancers Using Dendritic Cells (DCs)

Cervical Cancer Clinical Trial

Official title:

A Pilot Study for the Immunotherapy of Recurrent Cervical Cancers Using Dendritic Cells (DCs) Pulsed With Human Papillomavirus Type 16 E7 Antigen

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00155766
• Other study ID #: 9100205963
• Status: Recruiting
• Phase: Phase 1
• First received: September 9, 2005
• Last updated: December 19, 2005
• Start date: January 2003
• Est. completion date: March 2006

Study information

• Verified date: June 2002
• Source: National Taiwan University Hospital
• Contact: Chi-An Chen, MD
• Phone: 886-2-2312-3456
• Email: cachen[@]ha.mc.ntu.edu.tw
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Interventional

Clinical Trial Summary

Chemotherapy is the current standard treatment for unresectable recurrent cervical carcinoma after radiotherapy or distant metastasis of cervical carcinoma. The most effective regimens are cisplatin-based chemotherapy. After failure of the cisplatin-based chemotherapy, there is still no treatment that has been proved to be effective.

Human papilloma viruses (HPV) have been consistently implicated in causing cervical cancer especially those high-risk types (HPV 16,18,31,45) have been strongly associated with cervical cancer. HPV 16 was found in more than 50% of cervical cancer tissues. Results from many animal tumor models have indicated that immunization with tumor antigen-pulsed dendritic cells can trigger a long-lasting anti-tumor immune response and significantly inhibit the growth of implanted tumor cells. Recently, many clinical trials have been conducted to evaluate the feasibility and safety of immunizing cancer patients with tumor antigen-pulsed dendritic cells. No severe toxicity has been reported and some patients were shown to respond to the treatment. Based on previous animal and clinical studies by other investigators, we propose to evaluate the potential of immunizing cancer patients with antigen-pulsed autologous dendritic cells as a cancer vaccine to treat for recurrent cervical cancers after failure of cisplatin-based chemotherapy treatment or refusing chemotherapy. In this study, we will generate dendritic cells by culturing patient's autologous PBMC with GM-CSF and IL-4 in vitro. These dendritic cells will be pulsed with synthetic peptides representing the CTL epitopes on HPV Type 16 E7. Antigen-pulsed dendritic cells will be injected into inguinal lymph nodes under the guidance of real-time sonography. Each patient will receive four injections and 12 patients in total will be recruited for this study.

Description:

Chemotherapy is the current standard treatment for unresectable recurrent cervical carcinoma after radiotherapy or distant metastasis of cervical carcinoma. The most effective regimens are cisplatin-based chemotherapy. After failure of the cisplatin-based chemotherapy, there is still no treatment that has been proved to be effective.

Human papilloma viruses (HPV) have been consistently implicated in causing cervical cancer especially those high-risk types (HPV 16,18,31,45) have been strongly associated with cervical cancer. HPV 16 was found in more than 50% of cervical cancer tissues. Results from many animal tumor models have indicated that immunization with tumor antigen-pulsed dendritic cells can trigger a long-lasting anti-tumor immune response and significantly inhibit the growth of implanted tumor cells. Recently, many clinical trials have been conducted to evaluate the feasibility and safety of immunizing cancer patients with tumor antigen-pulsed dendritic cells. No severe toxicity has been reported and some patients were shown to respond to the treatment. Based on previous animal and clinical studies by other investigators, we propose to evaluate the potential of immunizing cancer patients with antigen-pulsed autologous dendritic cells as a cancer vaccine to treat for recurrent cervical cancers after failure of cisplatin-based chemotherapy treatment or refusing chemotherapy. In this study, we will generate dendritic cells by culturing patient's autologous PBMC with GM-CSF and IL-4 in vitro. These dendritic cells will be pulsed with synthetic peptides representing the CTL epitopes on HPV Type 16 E7. Antigen-pulsed dendritic cells will be injected into inguinal lymph nodes under the guidance of real-time sonography. Each patient will receive four injections and 12 patients in total will be recruited for this study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: March 2006
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. recurrent cervical cancer

2. HPV 16 infection

3. Previously received cisplatin ot 5-FU based chemotherapy or refused to receive chemotherapy

4. HLA-A2 haplotype

5. Older than 20 years old

6. ECOG I or II

7. Life expectancy longer than 3 months

8. Adequate bone marrow reserve

9. pregnancy test: negative

10. Informed consent obtained

Exclusion Criteria:

1. CNS metastasis

2. Acute or chronic infection

3. Pregnant or lactating women

4. Asthma

5. Cardiac diseases such as heart failure, unstable angina, arrhythmia, myocardial infarction

6. Autoimmune disease

7. Previously other cancers (except basal cell cancer)

8. Without chemotherapy, biotherapy for more than 6 weeks

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
• Uterine Cervical Neoplasms

Intervention

Biological:
• HPV16 E7 peptide-pulsed autologous DCs

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1. Safety issues in patients receiving HPV16 E7 peptide-pulsed autologous DCs immunotherapy
Secondary	1. Immunologic responses in patients receiving HPV16 E7 peptide-pulsed autologous DCs immunotherapy
Secondary	2. Clinical response in patients receiving HPV16 E7 peptide-pulsed autologous DCs immunotherapy