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

NCT ID: NCT00988559

Last Updated: 2018-07-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 132 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2016-07-31

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

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PMED Delivery - groups 1 and 2

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.

Group Type: EXPERIMENTAL

DNA vaccination

Intervention Type: BIOLOGICAL

vaccination with pNGVL4a-CRT/E7(detox)

Gene gun vaccine

Intervention Type: DEVICE

8 micrograms (group 1) or 16 micrograms (group 2)

therapeutic resection of the lesion

Intervention Type: PROCEDURE

at week 15, all residual lesions will be resected

IM injections - groups 5 and 6

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

Group Type: EXPERIMENTAL

DNA vaccination

Intervention Type: BIOLOGICAL

vaccination with pNGVL4a-CRT/E7(detox)

intramuscular vaccination

Intervention Type: BIOLOGICAL

1mg (group 3) or 3mg (group 4) of pNGVLra-CRT/E7(detox) administered intramuscularly

therapeutic resection of the lesion

Intervention Type: PROCEDURE

at week 15, all residual lesions will be resected

Intralesional delivery - group 3 and 4

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

Group Type: EXPERIMENTAL

DNA vaccination

Intervention Type: BIOLOGICAL

vaccination with pNGVL4a-CRT/E7(detox)

intra-lesional vaccine administration

Intervention Type: BIOLOGICAL

1mg (group 5) or 3mg (group 6) of pNGVL4a-CRT/E7(detox)administered intra-lesionally

therapeutic resection of the lesion

Intervention Type: PROCEDURE

at week 15, all residual lesions will be resected

Intralesional delivery + imiquimod - group 7

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.

Group Type: EXPERIMENTAL

DNA vaccination

Intervention Type: BIOLOGICAL

vaccination with pNGVL4a-CRT/E7(detox)

intra-lesional vaccine administration

Intervention Type: BIOLOGICAL

1mg (group 5) or 3mg (group 6) of pNGVL4a-CRT/E7(detox)administered intra-lesionally

therapeutic resection of the lesion

Intervention Type: PROCEDURE

at week 15, all residual lesions will be resected

imiquimod

Intervention Type: DRUG

imiquimod applied to the cervix by the physician

Interventions

DNA vaccination

vaccination with pNGVL4a-CRT/E7(detox)

Intervention Type: BIOLOGICAL

Gene gun vaccine

8 micrograms (group 1) or 16 micrograms (group 2)

Intervention Type: DEVICE

intramuscular vaccination

1mg (group 3) or 3mg (group 4) of pNGVLra-CRT/E7(detox) administered intramuscularly

Intervention Type: BIOLOGICAL

intra-lesional vaccine administration

1mg (group 5) or 3mg (group 6) of pNGVL4a-CRT/E7(detox)administered intra-lesionally

Intervention Type: BIOLOGICAL

therapeutic resection of the lesion

at week 15, all residual lesions will be resected

Intervention Type: PROCEDURE

imiquimod

imiquimod applied to the cervix by the physician

Intervention Type: DRUG

Other Intervention Names

Therapeutic vaccine; PMED administration; ND10 device; DNA vaccine; Intra-lesional DNA vaccination; LEEP or cold knife conization

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cornelia L Trimble, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

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

Countries

United States

Other Identifiers

P50CA098252

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1R21CA128232

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NA_00020850

Identifier Type: OTHER

Identifier Source: secondary_id

J0866

Identifier Type: -

Identifier Source: org_study_id