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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00988559
Recruitment Status : Completed
First Posted : October 2, 2009
Results First Posted : July 9, 2018
Last Update Posted : July 9, 2018
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Description
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Brief Summary:
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 or disease Intervention/treatment Phase
HPV16 Positive 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 Drug: imiquimod Phase 1

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
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 132 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (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)
Study Start Date : September 2009
Actual Primary Completion Date : July 2016
Actual Study Completion Date : July 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vaccines

Arms and Interventions
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Arm Intervention/treatment
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
Experimental: Intralesional delivery + imiquimod - group 7
Subjects will receive pNGVL4a-CRT/E7(detox) intra-mucosally and imiquimod applied to the cervix 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

Drug: imiquimod
imiquimod applied to the cervix by the physician


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants With Related Serious Adverse Events [ Time Frame: 9 months ]
    Presence of intervention-related serious adverse events as defined by CTCAE


Secondary Outcome Measures :
  1. Absence of CIN2/3 Lesion by Week 15 [ Time Frame: 15 weeks ]
    Number of participants with no CIN2/3 lesion at the week 15 visit


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes 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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00988559


Locations
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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Maryland
Johns Hopkins Outpatient Center
Baltimore, Maryland, United States, 21205
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, United States, 21224
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Cornelia L Trimble, MD Johns Hopkins University
More Information
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Additional Information:

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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT00988559    
Other Study ID Numbers: J0866
P50CA098252 ( U.S. NIH Grant/Contract )
1R21CA128232 ( U.S. NIH Grant/Contract )
NA_00020850 ( Other Identifier: JHM IRB )
First Posted: October 2, 2009    Key Record Dates
Results First Posted: July 9, 2018
Last Update Posted: July 9, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
high grade cervical dysplasia
treatment vaccine
therapeutic
HPV
 DNA vaccine
gene therapy
gene gun
pre-cancerous
Additional relevant MeSH terms:
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Neoplasms
Carcinoma in Situ
Uterine Cervical Dysplasia
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Precancerous Conditions
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Female Urogenital Diseases
 Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Genital Diseases
Imiquimod
Vaccines
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic
Antineoplastic Agents
Interferon Inducers