Clinical Trials /

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

NCT00988559

Description:

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.

Related Conditions:
  • High Grade Cervical Intraepithelial Neoplasia
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

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

Title

  • Brief Title: Therapeutic Vaccination for Patients With HPV16+ Cervical Intraepithelial Neoplasia (CIN2/3)
  • Official Title: A Pilot Study of pnGVL4a-CRT/E7 (Detox) for the Treatment of Patients With HPV16+ Cervical Intraepithelial Neoplasia 2/3 (CIN2/3)
  • Clinical Trial IDs

    NCT ID: NCT00988559

    ORG ID: J0866, NA_00020850

    NCI ID: P50CA098252

    Trial Conditions

    HPV16+

    Cervical Intraepithelial Neoplasia (CIN 2/3)

    Trial Interventions

    Drug Synonyms Arms
    imiquimod Intralesional delivery + imiquimod - group 7

    Trial 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.

    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

    Trial Arms

    Name Type Description Interventions
    PMED Delivery - groups 1 and 2 Experimental 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.
    IM injections - groups 5 and 6 Experimental Subjects will receive pNGVL4a-CRT/E7(detox) intramuscularly at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.
    Intralesional delivery - group 3 and 4 Experimental Subjects will receive pNGVL4a-CRT/E7(detox) intra-mucosally at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.
    Intralesional delivery + imiquimod - group 7 Experimental 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. imiquimod

    Eligibility 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.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    To evaluate feasibility and toxicity in women with CIN2/3 caused by HPV16

    Secondary Outcome Measures

    To compare immunogenicity of three different routes of administration: intradermal (ID), intramuscular (IM), and intralesional (IL)

    Trial Keywords

    high grade cervical dysplasia

    treatment vaccine

    therapeutic

    HPV

    DNA vaccine

    gene therapy

    gene gun

    pre-cancerous