Aerodigestive Precancerous Lesions and Malignancies
Conditions
Keywords
Aerodigestive Lesions and Malignancies, Human Papillomavirus, Squamous Cell Carcinoma
Brief summary
This is a Phase I, open-label study to evaluate the safety, tolerability, and immunogenicity of INO-3106 alone or in combination with INO-9012 DNA vaccines delivered by Electroporation to subjects with HPV6 associated aerodigestive precancerous lesions and malignancies.
Detailed description
This is a Phase I, open-label, study to evaluate the safety, tolerability, and immunogenicity of 3 mg or 6 mg INO-3106 alone or in combination with 1 mg of INO-9012 (DNA plasmid encoding human interleukin 12) delivered by electroporation (EP) in subjects with HPV6 associated aerodigestive precancerous lesions and malignancies. Subjects will be enrolled in 2 cohorts (3 subjects in each cohort): Cohort I: First 3 subjects will be enrolled sequentially and will receive INO-3106 alone or in combination with INO-9012. Cohort II: The next 3 subjects will be treated with 6 mg of INO-3106 and 1 mg of INO-9012, or at the MTD (Maximum Tolerated Dose) determined in Cohort I.
Interventions
BIOLOGICALINO-3106, INO-9012
Sponsors
University of Pennsylvania
Inovio Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed and dated written Ethics Committee approved informed consent * Age ≥18 years * Histologically documented HPV-6 positive aerodigestive invasive malignancy (mucosal squamous cell head and neck cancer or lung cancer) who have completed therapies such as radiation/chemoradiation/chemotherapy; or * Histologically documented HPV-6 positive papilloma or HPV-6 related premalignant lesion (i.e., carcinoma in situ) in aerodigestive or head and neck regions. * Prior to study entry, subjects will have exhausted all treatments that are/have been used in these indications which may include any combination of surgery, anti-viral therapy, chemotherapy and/or radiation therapy. * Core biopsy must be obtained prior to enrollment to confirm invasive cancer. Archival material is allowed. * Adequate bone marrow, hepatic, and renal function. ANC (Absolute Neutrophil Count) ≥ 1.5x109 cell/ml, platelets ≥75,000 cells/mm3, hemoglobin ≥ 9.0 g/dL, concentrations of total serum bilirubin within 1.5 x upper limit of normal (ULN), AST, ALT within 2.5x ULN, CPK within 2.5 x ULN, serum creatinine ≤ 1.5x ULN * ECOG (Eastern Cooperative Oncology Group) performance status of 0-2
Exclusion criteria
* Participation in a clinical trial within 30 days before entry * Any cardiac pre-excitation syndromes, e.g. Wolff-Parkinson-White syndrome * Presence of metal implants within 5 cm of the planned site(s) of injection * Anticipated concomitant immunosuppressive therapy (excluding non-systemic inhaled, topical skin and/or eye drop-containing corticosteroids) * Administration of any vaccine within 6 weeks of enrollment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse events measured and graded in accordance with Common Terminology Criteria for Adverse Events (CTCAE), NCI version 4.03 | Up to 6 months |
| Injection site reactions including skin erythema, induration pain and tenderness at administration site | Up to 15 weeks |
Secondary
| Measure | Time frame |
|---|---|
| HPV6 specific Ig levels | Up to 6 months |
| Number of antigen-specific IFN-γ-secreting cells in response to stimulation with HPV6 by antigen-specific IFN-γ ELISpot assays | Up to 6 months |
| Cytotoxic T cells in response to HPV6 specific immunotherapy by flow cytometry | Up to 6 months |
Other
| Measure | Time frame |
|---|---|
| Time to new anti-cancer therapy | First dose to Week 26 |
Countries
United States
Outcome results
None listed