Skip to main content
OpenTrials
Completed

NCT Number: NCT02163057

Study of HPV Specific Immunotherapy in Participants With HPV Associated Head and Neck Squamous Cell Carcinoma

This is a Phase I/IIa, open-label study to evaluate the safety, tolerability, and immunogenicity of INO-3112 DNA vaccine delivered by electroporation (EP) to participants with human papilloma virus (HPV) associated head and neck squamous cell cancer (HNSCC).

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Head and Neck Squamous Cell Cancer

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

About this study

This is a Phase I/IIa, open-label, study to evaluate the safety, tolerability, and immunogenicity of INO-3112 [6 mg of VGX-3100 (2 separate DNA plasmids respectively encoding E6 and E7 proteins of HPV 16 and HPV 18) and 1 mg of INO-9012 (DNA plasmid encoding human interleukin 12)] delivered by electroporation (EP) in up to 25 (twenty-five) participants with HPV positive head and neck cancer. The immunotherapy was studied in the following two groups of participants:

  • Participants who received immunotherapy before and after definitive surgery (Cohort I)
  • Participants who received immunotherapy at least 2 months after chemoradiation therapy (Cohort II).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Signed and dated written Ethics Committee approved informed consent.
  • Age ≥18 years.
  • Histologically confirmed HPV-positive (as assessed by p16 IHC or oncogenic HPV ISH or PCR) mucosal squamous cell head and neck cancer:
  • For pre-surgical participants, p16 positivity must be confirmed prior to the first dose.
  • For participants post-chemoradiation, HPV 16 and HPV 18 positivity must be confirmed prior to the first dose.
  • 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), (Aspartate Aminotransferase) AST, (Alanine Aminotransferase) ALT within 2.5x institutional ULN, (Creatine Phosphokinase) CPK within 2.5 x ULN.
  • ECOG (Eastern Cooperative Oncology Group) performance status of 0-1.

Exclusion criteria

  • Anticipated concomitant immunosuppressive therapy (excluding non-systemic inhaled, topical skin and/or eye drop-containing corticosteroids).
  • Any concurrent condition requiring the continued use of systemic steroids (>10 mg prednisone or equivalent per day) or the use of immunosuppressive agents. All other corticosteroids must be discontinued at least 4 weeks prior to Day 0 of treatment.
  • Administration of any vaccine within 6 weeks of enrollment.

Treatment and study plan

INO-3112

Biological

1.1 mL of INO-3112 (VGX-3100 + INO-9012) delivered intramuscularly (IM) followed immediately by electroporation (EP) with CELLECTRA™-5P device for a total of 4 doses of immunotherapy.

Other names: VGX-3100, INO-9012

CELLECTRA™-5P

Device

CELLECTRA™-5P device was used for EP following IM delivery of INO-3112 for a total of 4 doses of immunotherapy.

Primary outcomes

  1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Event (SAEs)

    Time frame: Up to 6 months post last dose

    An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body, or worsening of a pre-existing condition, temporally associated with the use of a product whether or not considered related to the use of the product. TEAE is defined as any AE with onset after the administration of study medication through the end-of-study follow-up, or any event that was present at baseline but worsened in intensity or was subsequently considered treatment-related by the Investigator through the end of the study. Serious adverse event (SAE) is defined as an event that meets 1 of the following criteria: is fatal or life-threatening, results in persistent or significant disability or incapacity, constitutes a congenital anomaly or birth defect, is clinically meaningful or requires inpatient hospitalization or prolongation of existing hospitalization.

Secondary outcomes

  1. E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA)

    Time frame: Up to 6 months post last dose

    Titers for HPV-16 and HPV-18 E6- and E7-specific antibodies were assessed by ELISA.

  2. E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA

    Time frame: Up to 6 months post last dose

    Titers for HPV-16 and HPV-18 E6- and E7-specific antibodies were assessed by ELISA.

  3. Change From Baseline (CFB) in Combined HPV-16 and HPV-18 E6 and E7 Antigen-Specific Spot-Forming Units Per Million Peripheral Blood Mononuclear Cell (SFU/10^6 PBMC) as Assessed by Enzyme-Linked Immunosorbent Spot-Forming Assay (ELISpot)

    Time frame: Baseline up to 6 months post last dose

  4. Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-16 as Assessed by Flow Cytometry

    Time frame: At baseline and Week 2 post last dose

    A flow cytometry assay called "lytic granule loading" was used to analyze CD8+ T cells specific for HPV-16 and CD8+ T cells specific for HPV-18 by evaluating the following markers: CD8, granzyme A (GrzA), granzyme B (GrzB), and perforin (Prf) co-expression with CD137, CD69, or CD38.

  5. Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-18 as Assessed by Flow Cytometry

    Time frame: At baseline and Week 2 post last dose

    A flow cytometry assay called "lytic granule loading" was used to analyze CD8+ T cells specific for HPV-16 and CD8+ T cells specific for HPV-18 by evaluating the following markers: CD8, granzyme A (GrzA), granzyme B (GrzB), and perforin (Prf) co-expression with CD137, CD69, or CD38.

  6. Mean Difference in Tumor Infiltrating Lymphocytes (TILs) in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC)

    Time frame: At screening and post-surgery

    The difference in means (post-surgery minus screening) for tumor-infiltrating lymphocytes (TILs) such as CD8, FoxP3, and perforin was analyzed using immunohistochemistry staining techniques.

  7. Mean Difference in CD8/FoxP3 Ratio in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC)

    Time frame: At screening and post-surgery

    The difference in means (post-surgery minus screening) for the CD8/FoxP3 ratio was analyzed using immunohistochemistry staining techniques.

  8. Phenotype of Cultured TILs

    Time frame: Up to 6 months post last dose

Sponsors and collaborators

Lead sponsor

Inovio Pharmaceuticals

Industry

Collaborators

  • University of Pennsylvania

Registry information

Official study title

Prospective Study of HPV Specific Immunotherapy in Subjects With HPV Associated Head and Neck Squamous Cell Carcinoma (HNSCCa)

Important dates

Study start
2014
Primary completion
2017
Study completion
2017
First posted
Jun 13, 2014
Registry last updated
Jan 22, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.