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

Phase 1

Completed

Conditions: HPV16 Positive
Cervical Intraepithelial Neoplasia (CIN 2/3)

Interventions: Biological: DNA vaccination
Device: Gene gun vaccine
Biological: intramuscular vaccination
Biological: intra-lesional vaccine administration
Procedure: therapeutic resection of the lesion
Drug: imiquimod

Registration Number: NCT00988559

Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

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

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 132

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intralesional delivery - group 3 and 4	therapeutic resection of the lesion	Subjects will receive pNGVL4a-CRT/E7(detox) intra-mucosally at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.
PMED Delivery - groups 1 and 2	DNA vaccination	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.
PMED Delivery - groups 1 and 2	Gene gun vaccine	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	intramuscular vaccination	Subjects will receive pNGVL4a-CRT/E7(detox) intramuscularly at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.
IM injections - groups 5 and 6	DNA vaccination	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	DNA vaccination	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	intra-lesional vaccine administration	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.
PMED Delivery - groups 1 and 2	therapeutic resection of the lesion	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.
Intralesional delivery + imiquimod - group 7	therapeutic resection of the lesion	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.
Intralesional delivery - group 3 and 4	intra-lesional vaccine administration	Subjects will receive pNGVL4a-CRT/E7(detox) intra-mucosally at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.
IM injections - groups 5 and 6	therapeutic resection of the lesion	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 + imiquimod - group 7	DNA vaccination	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.
Intralesional delivery + imiquimod - group 7	imiquimod	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Related Serious Adverse Events	9 months	Presence of intervention-related serious adverse events as defined by CTCAE

Secondary Outcome Measures

Name	Time	Method
Absence of CIN2/3 Lesion by Week 15	15 weeks	Number of participants with no CIN2/3 lesion at the week 15 visit

Trial Locations

Locations (3): University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Johns Hopkins Outpatient Center
🇺🇸
Baltimore, Maryland, United States
Johns Hopkins Bayview Medical Center
🇺🇸
Baltimore, Maryland, United States