Overview
Phase I clinical trial to assess safety of pNGVL4aCRTE6E7L2 DNA and TA-CIN protein vaccinations, and to seek the appropriate dose of the pNGVL4aCRTE6E7L2 DNA vaccine
Description
Primary Objectives
- To determine the safety and feasibility of intra-muscular administration of pNGVL4aCRTE6E7L2 DNA vaccine in patients with persistent HPV16+ ASC-US/LSIL.
- To determine the appropriate intra-muscular injection dose of pNGVL4aCRTE6E7L2 DNA vaccine as determined by toxicity and immunogenicity for a subsequent phase II clinical trial.
- To determine the safety and feasibility of intra-muscular administration of pNGVL4aCRTE6E7L2 DNA vaccine prime, TA-CIN protein vaccine boost in patients with persistent HPV16+ ASC-US/LSIL.
Eligibility
Inclusion Criteria:
- Patients with persistent (\>6 month period) ASC-US/LSIL determined by cervical cytology at study entry (ThinPrep with imaging)
- Patients whose cytologic samples are persistent (\>6 month period) HPV16+ by Roche Cobas 4800, Roche Linear Array HPV Genotyping test or other FDA-approved HPV genotyping test at study entry. Co-infections with HPV types other than HPV16 are permissible for study entry.
- Age ≥ 19 years
- Baseline Eastern Cooperative Oncology Group
- Patients must have adequate organ function at the time of enrollment as defined by the following parameters:
- White blood cell count \> 3,000
- Absolute lymphocyte number \> 500
- Absolute neutrophil count \> 1,000
- Platelets \> 90,000
- Hemoglobulin \> 9
- Total bilirubin \<3 X the institutional limit of normal
- AST(SGOT)/ALT(SGPT) \<3 X the institutional limit of normal
- Creatinine \< 2.5X the institutional limit of normal
- Women of child-bearing potential must agree to use two forms of contraception (hormonal and barrier) prior to study entry and for 3 months after study completion.
- Ability to understand and the willingness to sign a written informed consent document.
- Subject is able to adhere to the study visit schedule and other protocol requirements.
Exclusion Criteria:
- Patients with ASC-US/LSIL determined by cervical cytology at study entry that are HPV16 negative.
- Histologic evidence of CIN2+
- Patients with a diagnosis of immunosuppression or prolonged, active use of immunosuppressive medications such as steroids.
- Prior vaccination with any HPV antigen (prophylactic or therapeutic).
- Patients who are receiving any other investigational agents within 28 days prior to the first dose.
- Patients with an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients with a history of autoimmune disease such as multiple sclerosis, exclusive of a history of thyroiditis, psoriasis, Sjrogen's, or inflammatory bowel disease.
- Patients with a history of allergic reactions attributed to compounds used in agent preparation.
- Patients who are pregnant or breast feeding.
- Patient with active or chronic infection of HIV, HCV, or HBV.
- Patients who have had a prior LEEP or cervical conization procedure.
- History of prior malignancy permitted if patient has been disease free for ≥ 5 years; however individuals with completely resected basal cell or squamous cell carcinoma of the skin within this interval may be enrolled.
- Inability to understand or unwillingness to sign an informed consent document.
