Therapeutic Vaccination for Patients With HPV16+ Cervical Intraepithelial Neoplasia (CIN2/3)
Condition: HPV16 Positive; Cervical Intraepithelial Neoplasia (CIN 2/3)
MeSH terms: Neoplasms; Carcinoma in Situ; Uterine Cervical Dysplasia
Intervention: DNA vaccination; Gene gun vaccine; intramuscular vaccination; intra-lesional vaccine administration; therapeutic resection of the lesion; imiquimod
Intervention description: vaccination with pNGVL4a-CRT/E7(detox); 8 micrograms (group 1) or 16 micrograms (group 2); 1mg (group 3) or 3mg (group 4) of pNGVLra-CRT/E7(detox) administered intramuscularly; 1mg (group 5) or 3mg (group 6) of pNGVL4a-CRT/E7(detox)administered intra-lesionally; at week 15, all residual lesions will be resected; imiquimod applied to the cervix by the physician
Intervention MeSH terms: Imiquimod; Vaccines
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 132.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: high grade cervical dysplasia; treatment vaccine; therapeutic; HPV; DNA vaccine; gene therapy; gene gun; pre-cancerous

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.
    

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.