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

NCT00988559 | Completed Phase 1 Results DMC

• 4 other identifiers: J0866P50CA0982521R21CA128232NA_00020850
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 3

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Related Serious Adverse Events

  Presence of intervention-related serious adverse events as defined by CTCAE

  9 months

Secondary Outcomes (1)

• Absence of CIN2/3 Lesion by Week 15

  15 weeks

Study Arms (4)

PMED Delivery - groups 1 and 2

EXPERIMENTAL

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; Device: Gene gun vaccine; Procedure: therapeutic resection of the lesion

IM injections - groups 5 and 6

EXPERIMENTAL

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; Biological: intramuscular vaccination; Procedure: therapeutic resection of the lesion

Intralesional delivery - group 3 and 4

EXPERIMENTAL

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; Biological: intra-lesional vaccine administration; Procedure: therapeutic resection of the lesion

Intralesional delivery + imiquimod - group 7

EXPERIMENTAL

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; Biological: intra-lesional vaccine administration; Procedure: therapeutic resection of the lesion; Drug: imiquimod

Interventions

DNA vaccination BIOLOGICAL

vaccination with pNGVL4a-CRT/E7(detox)

Also known as: Therapeutic vaccine

IM injections - groups 5 and 6; Intralesional delivery + imiquimod - group 7; Intralesional delivery - group 3 and 4; PMED Delivery - groups 1 and 2

Gene gun vaccine DEVICE

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

Also known as: PMED administration, ND10 device

PMED Delivery - groups 1 and 2

intramuscular vaccination BIOLOGICAL

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

Also known as: DNA vaccine

IM injections - groups 5 and 6

intra-lesional vaccine administration BIOLOGICAL

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

Also known as: Intra-lesional DNA vaccination

Intralesional delivery + imiquimod - group 7; Intralesional delivery - group 3 and 4

therapeutic resection of the lesion PROCEDURE

at week 15, all residual lesions will be resected

Also known as: LEEP or cold knife conization

IM injections - groups 5 and 6; Intralesional delivery + imiquimod - group 7; Intralesional delivery - group 3 and 4; PMED Delivery - groups 1 and 2

imiquimod DRUG

imiquimod applied to the cervix by the physician

Intralesional delivery + imiquimod - group 7

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (3)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Johns Hopkins Outpatient Center

Baltimore, Maryland, 21205, United States

Location

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Uterine Cervical Dysplasia

Interventions

Vaccines; Vaccines, DNA; Conization; Imiquimod

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antigens; Biological Factors; Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Cornelia L. Trimble, MD
• Organization: Johns Hopkins University

ctrimbl@jhmi.edu

410-502-0512

Study Officials

• Cornelia L Trimble, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2009
• First Posted: October 2, 2009
• Study Start: September 1, 2009
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: July 9, 2018
• Results First Posted: July 9, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)