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

Johns Hopkins Medicine

Status and phase: Completed; Phase 1

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

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

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00988559

P50CA098252 (U.S. NIH Grant/Contract)

NA_00020850 (Other Identifier)

1R21CA128232 (U.S. NIH Grant/Contract)

J0866

Details and patient eligibility

About

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.

Full 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

Enrollment: 132 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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132 participants in 4 patient groups

PMED Delivery - groups 1 and 2

Experimental group

Description:

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.

Treatment:

Procedure: therapeutic resection of the lesion

Biological: DNA vaccination

Device: Gene gun vaccine

IM injections - groups 5 and 6

Experimental group

Description:

Subjects will receive pNGVL4a-CRT/E7(detox) intramuscularly at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

Treatment:

Procedure: therapeutic resection of the lesion

Biological: DNA vaccination

Biological: intramuscular vaccination

Intralesional delivery - group 3 and 4

Experimental group

Description:

Subjects will receive pNGVL4a-CRT/E7(detox) intra-mucosally at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

Treatment:

Biological: intra-lesional vaccine administration

Procedure: therapeutic resection of the lesion

Biological: DNA vaccination

Intralesional delivery + imiquimod - group 7

Experimental group

Description:

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.

Treatment:

Biological: intra-lesional vaccine administration

Procedure: therapeutic resection of the lesion

Drug: imiquimod

Biological: DNA vaccination