Immunotherapy of Recurrent Cervical Cancers Using Dendritic Cells (DCs)

NCT ID: NCT00155766

Last Updated: 2005-12-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-01-31
• Study Completion Date: 2006-03-31

Brief 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.

Detailed 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.

Conditions

Cervical Cancer

Keywords

cervical cancer, immunotherapy, DC

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

HPV16 E7 peptide-pulsed autologous DCs

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Taiwan University Hospital

OTHER

Sponsor Role: lead

Principal Investigators

Chi-An Chen, MD

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Locations

National Taiwan University Hospital

Taipei, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Chi-An Chen, MD

Role: CONTACT

Phone: 886-2-2312-3456

Email: cachen@ha.mc.ntu.edu.tw

Facility Contacts

Chi-An Chen, MD

Role: primary

Other Identifiers

9100205963

Identifier Type: -

Identifier Source: org_study_id