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.
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
Drug | Synonyms | Arms |
---|
DNA vaccination | Therapeutic vaccine | IM injections - groups 5 and 6 |
intramuscular vaccination | DNA vaccine | IM injections - groups 5 and 6 |
intra-lesional vaccine administration | Intra-lesional DNA vaccination | Intralesional delivery + imiquimod - group 7 |
imiquimod | | Intralesional 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
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. | - DNA vaccination
- intramuscular vaccination
|
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. | - DNA vaccination
- intra-lesional vaccine administration
|
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. | - 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