Clinical Trials /

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

NCT02241369

Description:

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.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Lung Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT02241369

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: HPV-006
  • NCT ID: NCT02241369

Conditions

  • Aerodigestive Precancerous Lesions and Malignancies

Interventions

DrugSynonymsArms
INO-3106, INO-9012Cohort I

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Cohort IExperimental3 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);
  • INO-3106, INO-9012
Cohort IIExperimental6 mg of INO-3106 in combination with 1 mg of INO-9012, or at the MTD determined above at D0, Wk3, Wk6, Wk9
  • INO-3106, INO-9012

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
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

Measure:HPV6 specific Ig levels
Time Frame:Up to 6 months
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Cytotoxic T cells in response to HPV6 specific immunotherapy by flow cytometry
Time Frame:Up to 6 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Inovio Pharmaceuticals

Trial Keywords

  • Aerodigestive Lesions and Malignancies
  • Human Papillomavirus
  • Squamous Cell Carcinoma

Last Updated

November 16, 2018