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

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

  • ORG STUDY ID: J0866
  • SECONDARY ID: P50CA098252
  • SECONDARY ID: 1R21CA128232
  • SECONDARY ID: NA_00020850
  • NCT ID: NCT00988559

Conditions

  • HPV16 Positive
  • Cervical Intraepithelial Neoplasia (CIN 2/3)

Interventions

DrugSynonymsArms
DNA vaccinationTherapeutic vaccineIM injections - groups 5 and 6
intramuscular vaccinationDNA vaccineIM injections - groups 5 and 6
intra-lesional vaccine administrationIntra-lesional DNA vaccinationIntralesional delivery + imiquimod - group 7
imiquimodIntralesional delivery + imiquimod - group 7

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

NameTypeDescriptionInterventions
PMED Delivery - groups 1 and 2ExperimentalSubjects will receive pNGVL4a-CRT/E7(detox) via gene gun at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.
  • DNA vaccination
IM injections - groups 5 and 6ExperimentalSubjects will receive pNGVL4a-CRT/E7(detox) intramuscularly at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.
  • DNA vaccination
  • intramuscular vaccination
Intralesional delivery - group 3 and 4ExperimentalSubjects will receive pNGVL4a-CRT/E7(detox) intra-mucosally at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.
  • DNA vaccination
  • intra-lesional vaccine administration
Intralesional delivery + imiquimod - group 7ExperimentalSubjects 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.
  • DNA vaccination
  • intra-lesional vaccine administration
  • 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants With Related Serious Adverse Events
Time Frame:9 months
Safety Issue:
Description:Presence of intervention-related serious adverse events as defined by CTCAE

Secondary Outcome Measures

Measure:Absence of CIN2/3 Lesion by Week 15
Time Frame:15 weeks
Safety Issue:
Description:Number of participants with no CIN2/3 lesion at the week 15 visit

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Trial Keywords

  • high grade cervical dysplasia
  • treatment vaccine
  • therapeutic
  • HPV
  • DNA vaccine
  • gene therapy
  • gene gun
  • pre-cancerous

Last Updated

July 9, 2018