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A Pair of Vaccinations (pNGVL4aCRTE6E7L2) and (TA-CIN) for the Treatment of Patients with HPV16 Positive Cervical Neoplasia
Trial Status: active
This phase I trial tests the safety, side effects, and best dose of pNGVL4a-CRTE6E7L2 DNA (pNGVL4aCRTE6E7L2) vaccine when given alone or together with HPV16 L2/E6/E7 fusion protein vaccine (TA-CIN) in treating patients with human papillomavirus 16 (HPV16) positive precancerous lesions (neoplasia) in the cervix. Scientist have found that a family of viruses called the high risk human papilloma viruses (hrHPV) can cause cancer that derives from the uterine cervix, the mouth of the womb, also called cervical cancer. Most cervical cancers are caused by a type of human papillomavirus (HPV) called HPV16. The pNGVL4aCRTE6E7L2 vaccine is made up of a circular DNA molecule that produces three proteins from the HPV16 virus, HPV16 E6, E7 and L2 proteins, joined together. The pNGVL4aCRTE6E7L2 vaccine may be able to teach the body’s immune system to recognize and get rid of the HPV16 virus. The TA-CIN vaccine is made up of three proteins from the HPV16 virus, HPV16 L2, E7 and E6, fused together. The TA-CIN vaccine may also teach the body’s immune system to recognize and get rid of the HPV16 virus. Giving the pNGVL4aCRTE6E7L2 vaccine together with the TA-CIN vaccine may be safe, tolerable and/or effective in treating patients with HPV16 positive cervical neoplasia.
Inclusion Criteria
Patients with ASC-US/LSIL/ASC-H determined by cervical cytology at study entry (thinprep with imaging) or normal cytology (NILM) with CIN1 upon biopsy
Patients whose cytologic samples are HPV16+ by roche cobas 4800 or other Food and Drug Administration (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 performance status of 0, 1 at the time of multi-modality treatment administration
White blood cell count > 3,000/ mcL
Absolute lymphocyte number > 500/mcL
Absolute neutrophil count > 1,500/mcL
Platelets > 90,000/mcL
Hemoglobulin > 9.0 g/dL
Total bilirubin < 3 X the institutional limit of normal
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [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 long acting contraception (e.g. tubal ligation, intrauterine device or hormonal implant) or two forms of contraception (e.g. barrier method, oral contraceptives) prior to study entry and for 3 months after final vaccination
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
Histologic evidence of CIN2, CIN3, adenocarcinoma in situ or malignancy
Patients with a diagnosis of immunosuppression or prolonged, active use of systemic immunosuppressive medications such as steroids
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 or plan to become pregnant within five months of first study treatment
Patient with active or chronic infection of HIV, hepatitis C virus (HCV), or hepatitis B virus (HBV)
History of prior malignancy 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
Additional locations may be listed on ClinicalTrials.gov for NCT03913117.
I. To determine the safety and feasibility of intramuscular administration of pNGVL4a-CRTE6E7L2 DNA vaccine in patients with HPV16+ ASC-US/ASC-H/LSIL/CIN1.
II. To determine the appropriate intramuscular injection dose of pNGVL4a-CRTE6E7L2 DNA vaccine, as determined by toxicity and immunogenicity for a subsequent phase II clinical trial.
III. To determine the safety and feasibility of intramuscular administration of pNGVL4a-CRTE6E7L2 DNA vaccine prime, TA-CIN protein vaccine boost in patients with HPV16+ ASC-US/ASC-H/LSIL/CIN1.
SECONDARY OBJECTIVES:
I. To evaluate the levels of circulating antibody specific for HPV16 in the peripheral blood pre- and post-vaccination.
II. To evaluate the levels of circulating HPV16 E6/E7-specific CD8+ T cells and T regulatory cells in the peripheral blood pre- and post-vaccination.
III. To evaluate the presence of high-risk HPV, and specifically HPV16 in cytologic specimens pre- and post-vaccination.
IV. To evaluate changes in the cytopathology of ectocervical and endocervical specimens taken pre- and post-vaccination.
V. To evaluate changes in the histology of cervical specimens taken pre- and post-vaccination.
OUTLINE: This is a dose-escalation study of pNGVL4a-CRTE6E7L2 vaccine, followed by a dose-expansion study. Patients are assigned to 1 of 2 cohorts.
COHORT I (DNA VACCINE DOSE ESCALATION AND EXPANSION): Patients receive pNGVL4a-CRTE6E7L2 vaccine intramuscularly (IM) in the right upper thigh muscle on day 1 of weeks 0, 4, and 8 in the absence of disease progression or unacceptable toxicity.
COHORT II (DNA-PRIME, PROTEIN-BOOST): Patients receive pNGVL4a-CRTE6E7L2 vaccine (IM) in the right upper thigh muscle on day 1 of week 0 and 4 and TA-CIN IM in the right upper thigh muscle on day 1 of week 8 in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, colposcopy, cervical biopsy, and endocervical curettage throughout the trial.
Upon completion of study treatment, patients are followed up at 1 week, 1 month, 6 months, and 12 months after last dose of the study drug.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationUniversity of Alabama at Birmingham Cancer Center
