search
Back to results

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

Primary Purpose

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

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
DNA vaccination
Gene gun vaccine
intramuscular vaccination
intra-lesional vaccine administration
therapeutic resection of the lesion
imiquimod
Sponsored by
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HPV16 Positive focused on measuring high grade cervical dysplasia, treatment vaccine, therapeutic, HPV, DNA vaccine, gene therapy, gene gun, pre-cancerous

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept 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.

Sites / Locations

  • University of Alabama at Birmingham
  • Johns Hopkins Outpatient Center
  • Johns Hopkins Bayview Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

PMED Delivery - groups 1 and 2

IM injections - groups 5 and 6

Intralesional delivery - group 3 and 4

Intralesional delivery + imiquimod - group 7

Arm 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.

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

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

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.

Outcomes

Primary Outcome Measures

Number of Participants With Related Serious Adverse Events
Presence of intervention-related serious adverse events as defined by CTCAE

Secondary Outcome Measures

Absence of CIN2/3 Lesion by Week 15
Number of participants with no CIN2/3 lesion at the week 15 visit

Full Information

First Posted
October 1, 2009
Last Updated
July 6, 2018
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Institutes of Health (NIH), National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00988559
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)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
September 2009 (undefined)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
July 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Institutes of Health (NIH), National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HPV16 Positive, Cervical Intraepithelial Neoplasia (CIN 2/3)
Keywords
high grade cervical dysplasia, treatment vaccine, therapeutic, HPV, DNA vaccine, gene therapy, gene gun, pre-cancerous

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
132 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PMED Delivery - groups 1 and 2
Arm Type
Experimental
Arm 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.
Arm Title
IM injections - groups 5 and 6
Arm Type
Experimental
Arm Description
Subjects will receive pNGVL4a-CRT/E7(detox) intramuscularly at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.
Arm Title
Intralesional delivery - group 3 and 4
Arm Type
Experimental
Arm 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.
Arm Title
Intralesional delivery + imiquimod - group 7
Arm Type
Experimental
Arm 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.
Intervention Type
Biological
Intervention Name(s)
DNA vaccination
Other Intervention Name(s)
Therapeutic vaccine
Intervention Description
vaccination with pNGVL4a-CRT/E7(detox)
Intervention Type
Device
Intervention Name(s)
Gene gun vaccine
Other Intervention Name(s)
PMED administration, ND10 device
Intervention Description
8 micrograms (group 1) or 16 micrograms (group 2)
Intervention Type
Biological
Intervention Name(s)
intramuscular vaccination
Other Intervention Name(s)
DNA vaccine
Intervention Description
1mg (group 3) or 3mg (group 4) of pNGVLra-CRT/E7(detox) administered intramuscularly
Intervention Type
Biological
Intervention Name(s)
intra-lesional vaccine administration
Other Intervention Name(s)
Intra-lesional DNA vaccination
Intervention Description
1mg (group 5) or 3mg (group 6) of pNGVL4a-CRT/E7(detox)administered intra-lesionally
Intervention Type
Procedure
Intervention Name(s)
therapeutic resection of the lesion
Other Intervention Name(s)
LEEP or cold knife conization
Intervention Description
at week 15, all residual lesions will be resected
Intervention Type
Drug
Intervention Name(s)
imiquimod
Intervention Description
imiquimod applied to the cervix by the physician
Primary Outcome Measure Information:
Title
Number of Participants With Related Serious Adverse Events
Description
Presence of intervention-related serious adverse events as defined by CTCAE
Time Frame
9 months
Secondary Outcome Measure Information:
Title
Absence of CIN2/3 Lesion by Week 15
Description
Number of participants with no CIN2/3 lesion at the week 15 visit
Time Frame
15 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cornelia L Trimble, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Johns Hopkins Outpatient Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Johns Hopkins Bayview Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.hopkinsmedicine.org/cervicaldysplasia
Description
Johns Hopkins Center for Cervical Dysplasia

Learn more about this trial

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

We'll reach out to this number within 24 hrs