Clinical trial NCT02241369: Immunotherapy in Subjects With HPV-6 Associated Aerodigestive Precancerous Lesions and Malignancies
Official title: A Study of HPV Specific Immunotherapy in Subjects With HPV6 Associated Aerodigestive Precancerous Lesions and Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Aerodigestive Precancerous Lesions and Malignancies
Keywords: Aerodigestive Lesions and Malignancies
Human Papillomavirus
Squamous Cell Carcinoma
Lead sponsor: Inovio Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: University of Pennsylvania
First posted: 2014-09-16
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Adverse events measured and graded in accordance with "Common Terminology Criteria for Adverse Events (CTCAE)", NCI version 4.03
timeFrame: Up to 6 months
measure: Injection site reactions including skin erythema, induration pain and tenderness at administration site
timeFrame: Up to 15 weeks
Secondary outcomes:
measure: HPV6 specific Ig levels
timeFrame: Up to 6 months
measure: Number of antigen-specific IFN-γ-secreting cells in response to stimulation with HPV6 by antigen-specific IFN-γ ELISpot assays
timeFrame: Up to 6 months
measure: Cytotoxic T cells in response to HPV6 specific immunotherapy by flow cytometry
timeFrame: Up to 6 months
Other outcomes:
measure: Time to new anti-cancer therapy
timeFrame: First dose to Week 26
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Inovio Pharmaceuticals
name: Jeffrey Skolnik, MD
role: STUDY_DIRECTOR
References: