Therapeutic Vaccination for Patients With HPV16+ Cervical Intraepithelial Neoplasia (CIN2/3) - Full Text View

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:

MedlinePlus related topics: Cancer

Drug Information available for: Deoxyribonucleic acid

U.S. FDA Resources

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 2013
Estimated Primary Completion Date:	September 2013 (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

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

Contacts

Contact: Cornelia L Trimble, MD

410-502-0512

ctrimbl@jhmi.edu

Locations

United States, Alabama
University of Alabama at Birmingham	Not yet 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

National Institutes of Health (NIH)

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Cornelia L Trimble, MD

Johns Hopkins University

More Information

Additional Information:

Johns Hopkins Center for Cervical Dysplasia This link exits the ClinicalTrials.gov site

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:	October 11, 2012
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 May 23, 2013