Immunotherapy in Subjects With HPV-6 Associated Aerodigestive Precancerous Lesions and Malignancies

• ClinicalTrials.gov Identifier: NCT02241369
• Recruitment Status: Completed
• First Posted: September 16, 2014
• Last Update Posted: November 16, 2018
• Sponsor: Inovio Pharmaceuticals
• Collaborator: University of Pennsylvania
• Information provided by (Responsible Party): Inovio Pharmaceuticals

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Aerodigestive Precancerous Lesions and Malignancies	Biological: INO-3106, INO-9012	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Study of HPV Specific Immunotherapy in Subjects With HPV6 Associated Aerodigestive Precancerous Lesions and Malignancies
• Study Start Date: May 2014
• Actual Primary Completion Date: September 2018
• Actual Study Completion Date: September 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort I; 3 mg of INO-3106 (D0); 6 mg of INO-3106 (Wk3); 6 mg of INO-3106 + 1 mg of INO-9012 (Wk6); 6 mg of INO-3106 + 1 mg of INO-9012 (Wk9);	Biological: INO-3106, INO-9012
Experimental: Cohort II; 6 mg of INO-3106 in combination with 1 mg of INO-9012, or at the MTD determined above at D0, Wk3, Wk6, Wk9	Biological: INO-3106, INO-9012

Outcome Measures

Primary Outcome Measures :

1. Adverse events measured and graded in accordance with "Common Terminology Criteria for Adverse Events (CTCAE)", NCI version 4.03 [ Time Frame: Up to 6 months ]
2. Injection site reactions including skin erythema, induration pain and tenderness at administration site [ Time Frame: Up to 15 weeks ]

Secondary Outcome Measures :

1. HPV6 specific Ig levels [ Time Frame: Up to 6 months ]
2. Number of antigen-specific IFN-γ-secreting cells in response to stimulation with HPV6 by antigen-specific IFN-γ ELISpot assays [ Time Frame: Up to 6 months ]
3. Cytotoxic T cells in response to HPV6 specific immunotherapy by flow cytometry [ Time Frame: Up to 6 months ]

Other Outcome Measures:

1. Time to new anti-cancer therapy [ Time Frame: First dose to Week 26 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Inovio Pharmaceuticals

University of Pennsylvania

Investigators

• Study Director: Jeffrey Skolnik, MD; Inovio Pharmaceuticals

More Information

Additional Information:

Sponsor's Website 

• Responsible Party: Inovio Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02241369
• Other Study ID Numbers: HPV-006
• First Posted: September 16, 2014
• Last Update Posted: November 16, 2018
• Last Verified: November 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Inovio Pharmaceuticals:

Aerodigestive Lesions and Malignancies; Human Papillomavirus; Squamous Cell Carcinoma

Additional relevant MeSH terms:

Neoplasms