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

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

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.

Study Overview

• Status: Completed
• Conditions: HPV16 Positive; Cervical Intraepithelial Neoplasia (CIN 2/3)
• Intervention / Treatment: Biological: DNA vaccination; Device: Gene gun vaccine; Procedure: therapeutic resection of the lesion; Biological: intramuscular vaccination; Biological: intra-lesional vaccine administration; Drug: imiquimod

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

• Study Type: Interventional
• Enrollment (Actual): 132
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins Outpatient Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH)

Publications and helpful links

Helpful Links

• Johns Hopkins Center for Cervical Dysplasia

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (ACTUAL): July 1, 2016
• Study Completion (ACTUAL): July 1, 2016

Study Registration Dates

• First Submitted: October 1, 2009
• First Submitted That Met QC Criteria: October 1, 2009
• First Posted (ESTIMATE): October 2, 2009

Study Record Updates

• Last Update Posted (ACTUAL): July 9, 2018
• Last Update Submitted That Met QC Criteria: July 6, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: gene therapy; therapeutic; HPV; DNA vaccine; high grade cervical dysplasia; treatment vaccine; gene gun; pre-cancerous
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms; Carcinoma in Situ; Cervical Intraepithelial Neoplasia; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Interferon Inducers; Vaccines; Imiquimod
• Other Study ID Numbers: J0866; P50CA098252 (U.S. NIH Grant/Contract); 1R21CA128232 (NIH); NA_00020850 (OTHER: JHM IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO