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

Study Overview
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Brief Summary
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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
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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

Official Title
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A Pilot Study of pnGVL4a-CRT/E7 (Detox) for the Treatment of Patients With HPV16+ Cervical Intraepithelial Neoplasia 2/3 (CIN2/3)

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

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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PMED Delivery - groups 1 and 2<br>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<br>* vaccination with pNGVL4a-CRT/E7(detox)<br>* Other names: Therapeutic vaccine;Device: Gene gun vaccine<br>* 8 micrograms (group 1) or 16 micrograms (group 2)<br>* Other names: ND10 device;Procedure: therapeutic resection of the lesion<br>* at week 15, all residual lesions will be resected<br>* Other names: LEEP or cold knife conization;|
| Experimental: IM injections - groups 5 and 6<br>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<br>* vaccination with pNGVL4a-CRT/E7(detox)<br>* Other names: Therapeutic vaccine;Biological: intramuscular vaccination<br>* 1mg (group 3) or 3mg (group 4) of pNGVLra-CRT/E7(detox) administered intramuscularly<br>* Other names: DNA vaccine;Procedure: therapeutic resection of the lesion<br>* at week 15, all residual lesions will be resected<br>* Other names: LEEP or cold knife conization;|
| Experimental: Intralesional delivery - group 3 and 4<br>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<br>* vaccination with pNGVL4a-CRT/E7(detox)<br>* Other names: Therapeutic vaccine;Biological: intra-lesional vaccine administration<br>* 1mg (group 5) or 3mg (group 6) of pNGVL4a-CRT/E7(detox)administered intra-lesionally<br>* Other names: Intra-lesional DNA vaccination;Procedure: therapeutic resection of the lesion<br>* at week 15, all residual lesions will be resected<br>* Other names: LEEP or cold knife conization;|
| Experimental: Intralesional delivery + imiquimod - group 7<br>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<br>* vaccination with pNGVL4a-CRT/E7(detox)<br>* Other names: Therapeutic vaccine;Biological: intra-lesional vaccine administration<br>* 1mg (group 5) or 3mg (group 6) of pNGVL4a-CRT/E7(detox)administered intra-lesionally<br>* Other names: Intra-lesional DNA vaccination;Procedure: therapeutic resection of the lesion<br>* at week 15, all residual lesions will be resected<br>* Other names: LEEP or cold knife conization;Drug: imiquimod<br>* imiquimod applied to the cervix by the physician<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absence of CIN2/3 Lesion by Week 15 | Number of participants with no CIN2/3 lesion at the week 15 visit | 15 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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high grade cervical dysplasia, treatment vaccine, therapeutic, HPV, DNA vaccine, gene therapy, gene gun, pre-cancerous