Therapeutic Vaccination for Patients With HPV16+ Cervical Intraepithelial Neoplasia (CIN2/3)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00988559
First received: October 1, 2009
Last updated: March 23, 2014
Last verified: March 2014
  Purpose

This study will test the efficacy and safety of different routes of administration of a DNA vaccine in patients with HPV16+ CIN2/3. Subjects will be enrolled in one of six treatment groups. Subjects enrolled in the first two groups will receive vaccination intradermally with a needle-free delivery device. Subjects enrolled in groups 3 and 4 will receive vaccination intramuscularly. Subjects enrolled in groups 5 and 6 will receive vaccine intralesionally.


Condition Intervention
HPV16+
Cervical Intraepithelial Neoplasia (CIN 2/3)
Biological: DNA vaccination
Device: Gene gun vaccine
Biological: intramuscular vaccination
Biological: intra-lesional vaccine administration
Procedure: therapeutic resection of the lesion

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of pnGVL4a-CRT/E7 (Detox) for the Treatment of Patients With HPV16+ Cervical Intraepithelial Neoplasia 2/3 (CIN2/3)

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • To evaluate feasibility and toxicity in women with CIN2/3 caused by HPV16 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To compare immunogenicity of three different routes of administration: intradermal (ID), intramuscular (IM), and intralesional (IL) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 39
Study Start Date: September 2009
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PMED Delivery - groups 1 and 2
Subjects will receive pNGVL4a-CRT/E7(detox) via gene gun at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.
Biological: DNA vaccination
vaccination with pNGVL4a-CRT/E7(detox)
Other Name: Therapeutic vaccine
Device: Gene gun vaccine
8 micrograms (group 1) or 16 micrograms (group 2)
Other Names:
  • PMED administration
  • ND10 device
Procedure: therapeutic resection of the lesion
at week 15, all residual lesions will be resected
Other Name: LEEP or cold knife conization
Experimental: IM injections - groups 5 and 6
Subjects will receive pNGVL4a-CRT/E7(detox) intramuscularly at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.
Biological: DNA vaccination
vaccination with pNGVL4a-CRT/E7(detox)
Other Name: Therapeutic vaccine
Biological: intramuscular vaccination
1mg (group 3) or 3mg (group 4) of pNGVLra-CRT/E7(detox) administered intramuscularly
Other Name: DNA vaccine
Procedure: therapeutic resection of the lesion
at week 15, all residual lesions will be resected
Other Name: LEEP or cold knife conization
Experimental: Intralesional delivery - group 3 and 4
Subjects will receive pNGVL4a-CRT/E7(detox) intra-mucosally at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.
Biological: DNA vaccination
vaccination with pNGVL4a-CRT/E7(detox)
Other Name: Therapeutic vaccine
Biological: intra-lesional vaccine administration
1mg (group 5) or 3mg (group 6) of pNGVL4a-CRT/E7(detox)administered intra-lesionally
Other Name: Intra-lesional DNA vaccination
Procedure: therapeutic resection of the lesion
at week 15, all residual lesions will be resected
Other Name: LEEP or cold knife conization

Detailed Description:

Primary Objectives

  • To evaluate the feasibility and toxicity of vaccination in women with CIN2/3 caused by HPV16
  • To evaluate the effect of vaccination on histology
  • To compare immunogenicity of three different routes of administration: intradermal (ID), intramuscular (IM), intralesional (IL).

Secondary Objectives:

  • To evaluate changes in HPV viral load
  • To evaluate the cellular immune response to vaccination
  • To evaluate the humoral immune response to vaccination
  • To evaluate local tissue immune response
  • To correlate measures of immune response with clinical response
  • To correlate measures of immune response with those observed in the preclinical model
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • patients with high grade cervical intraepithelial lesions (CIN2/3)
  • patients whose lesions are HPV16+
  • patients who are age 18 or older
  • patients who are able to give informed consent
  • patients who are immunocompetent
  • patients who are not pregnant, committed to using adequate contraception if of childbearing age
  • patients who have a minimum hemoglobin level of 9

Exclusion Criteria:

  • Patients with cytologic evidence of glandular dysplasia
  • Patients with cytologic evidence of adenocarcinoma in situ
  • Patients who are pregnant
  • Patients with an active autoimmune disease
  • Patients who are taking immunosuppressive medication
  • Patients with concurrent malignancy except for nonmelanoma skin lesions
  • Patients who have an allergy to gold.
  • Patients with any evidence of damaged skin, or moles, scars, tattoos or marks at the proposed site(s) of administration that might interfere with the interpretation of local skin reactions.
  • History or evidence of a physician-diagnosed chronic or recurrent inflammatory skin disease (e.g. psoriasis, eczema, atopic dermatitis, hypersensitivity) at the proposed site of administration in the past 5 years.
  • Patients who have an active autoimmune disease or history of autoimmune disease requiring medical treatment with systemic immunosuppressants, including: inflammatory bowel disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemic, or immune thrombocytopenia, rheumatoid arthritis, SLE, and Sjogren's syndrome, sarcoidosis. Asthma or COPD that does not require systemic corticosteroids or routine use of inhaled steroids is acceptable
  • Patients who have received prior chrysotherapy (administration of gold salts to treat rheumatoid arthritis).
  • Patients with a history of arterial or venous thrombosis
  • Patients with non-healed wounds.
  • Patients with a history of keloid formation ( ID delivery group only)
  • Patients with a history of hepatitis B with persistent infection.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00988559

Contacts
Contact: Clinical Trials Office Sidney Kimmel Comprehensive Cancer Center 410-955-8804 jhcccro@jhmi.edu

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Warner K Huh, MD    205-996-4662    warner.huh@ccc.uab.edu   
Contact: Ronald Alvarez, MD    205-996-4662    ronald.alvarez@ccc.uab.edu   
Principal Investigator: Warner K Huh, MD         
Sub-Investigator: Ronald Alvarez, MD         
United States, Maryland
Johns Hopkins Outpatient Center Recruiting
Baltimore, Maryland, United States, 21205
Contact: Cornelia Trimble, MD    410-502-0512    ctrimbl@jhmi.edu   
Contact: Mihaela Paradis, BA    410-502-0512    mparadis@jhmi.edu   
Principal Investigator: Cornelia L Trimble, MD         
Johns Hopkins Bayview Medical Center Recruiting
Baltimore, Maryland, United States, 21224
Contact: Cornelia Trimble, MD    410-502-0512    ctrimbl@jhmi.edu   
Contact: Mihaela Paradis, BA    410-502-0512    mparadis@jhmi.edu   
Principal Investigator: Cornelia L Trimble, MD         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Principal Investigator: Cornelia L Trimble, MD Johns Hopkins University
  More Information

Additional Information:
No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00988559     History of Changes
Other Study ID Numbers: J0866, NA_00020850, P50CA098252, 1R21CA128232
Study First Received: October 1, 2009
Last Updated: March 23, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
high grade cervical dysplasia
treatment vaccine
therapeutic
HPV
DNA vaccine
gene therapy
gene gun
pre-cancerous

Additional relevant MeSH terms:
Neoplasms
Cervical Intraepithelial Neoplasia
Carcinoma in Situ
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on August 25, 2014