Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02163057
Recruitment Status : Completed
First Posted : June 13, 2014
Results First Posted : December 23, 2020
Last Update Posted : January 22, 2021
Sponsor:
Collaborator:
University of Pennsylvania
Information provided by (Responsible Party):
Inovio Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE June 10, 2014
First Posted Date  ICMJE June 13, 2014
Results First Submitted Date  ICMJE December 1, 2020
Results First Posted Date  ICMJE December 23, 2020
Last Update Posted Date January 22, 2021
Actual Study Start Date  ICMJE August 13, 2014
Actual Primary Completion Date January 23, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 1, 2020)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 12, 2014)
Safety and Tolerability of VGX-3100 and INO-9012 delivered via IM EP [ Time Frame: 2 years ]
Evaluate the safety and tolerability of immunotherapy with VGX-3100 and INO-9012 when delivered intramuscularly followed by electroporation with CELLECTRA®-5P in patients with HPV associated Head and Neck Cancer. Adverse events and Injection site reactions will be measured
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 1, 2020)
  • 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.
  • 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.
  • 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 ]
  • 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.
  • 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.
  • 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.
  • 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.
  • Phenotype of Cultured TILs [ Time Frame: Up to 6 months post last dose ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 12, 2014)
Immunogenicity of VGX-3100 and INO-9012 delivered via IM EP [ Time Frame: 2 years ]
Evaluate the cellular and humoral immune responses to immunotherapy with VGX-3100 and INO-9012 delivered by electroporation with CELLECTRA®-5P in patients with HPV associated Head and Neck cancer Measure Ig levels, IFN-γ-secreting cells and cytotoxic T cells in response to HPV specific immunotherapy.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of HPV Specific Immunotherapy in Participants With HPV Associated Head and Neck Squamous Cell Carcinoma
Official Title  ICMJE Prospective Study of HPV Specific Immunotherapy in Subjects With HPV Associated Head and Neck Squamous Cell Carcinoma (HNSCCa)
Brief Summary 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).
Detailed Description

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:

  1. Participants who received immunotherapy before and after definitive surgery (Cohort I)
  2. Participants who received immunotherapy at least 2 months after chemoradiation therapy (Cohort II).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Head and Neck Squamous Cell Cancer
Intervention  ICMJE
  • Biological: INO-3112
    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
  • Device: CELLECTRA™-5P
    CELLECTRA™-5P device was used for EP following IM delivery of INO-3112 for a total of 4 doses of immunotherapy.
Study Arms  ICMJE
  • Cohort 1: Surgery Cohort
    Participants received up to two doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart before surgery and up to three doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart after surgery for a total of no more than four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device.
    Interventions:
    • Biological: INO-3112
    • Device: CELLECTRA™-5P
  • Cohort 2: Chemoradiation
    Participants received four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device 3 weeks (± 3 days) apart beginning approximately 2 to 6 months after chemoradiation therapy.
    Interventions:
    • Biological: INO-3112
    • Device: CELLECTRA™-5P
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 3, 2016)
22
Original Estimated Enrollment  ICMJE
 (submitted: June 12, 2014)
20
Actual Study Completion Date  ICMJE January 23, 2017
Actual Primary Completion Date January 23, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Signed and dated written Ethics Committee approved informed consent.
  2. Age ≥18 years.
  3. 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.
  4. 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.
  5. ECOG (Eastern Cooperative Oncology Group) performance status of 0-1.

Exclusion Criteria:

  1. Anticipated concomitant immunosuppressive therapy (excluding non-systemic inhaled, topical skin and/or eye drop-containing corticosteroids).
  2. 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.
  3. Administration of any vaccine within 6 weeks of enrollment.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02163057
Other Study ID Numbers  ICMJE HPV-005
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Inovio Pharmaceuticals
Study Sponsor  ICMJE Inovio Pharmaceuticals
Collaborators  ICMJE University of Pennsylvania
Investigators  ICMJE
Study Director: Jeffrey Skolnik, MD Inovio Pharmaceuticals
PRS Account Inovio Pharmaceuticals
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP