Clinical trial NCT02163057: Study of HPV Specific Immunotherapy in Participants With HPV Associated Head and Neck Squamous Cell Carcinoma
Official title: Prospective Study of HPV Specific Immunotherapy in Subjects With HPV Associated Head and Neck Squamous Cell Carcinoma (HNSCCa)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Head and Neck Squamous Cell Cancer
Keywords: Head and neck squamous cell cancer
Papillomavirus
Lead sponsor: Inovio Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: University of Pennsylvania
First posted: 2014-06-13
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Event (SAEs)
timeFrame: Up to 6 months post last dose
Secondary outcomes:
measure: E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA)
timeFrame: Up to 6 months post last dose
measure: E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA
timeFrame: Up to 6 months post last dose
measure: 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)
timeFrame: Baseline up to 6 months post last dose
measure: Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-16 as Assessed by Flow Cytometry
timeFrame: At baseline and Week 2 post last dose
measure: Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-18 as Assessed by Flow Cytometry
timeFrame: At baseline and Week 2 post last dose
measure: Mean Difference in Tumor Infiltrating Lymphocytes (TILs) in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC)
timeFrame: At screening and post-surgery
measure: Mean Difference in CD8/FoxP3 Ratio in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC)
timeFrame: At screening and post-surgery
measure: Phenotype of Cultured TILs
timeFrame: Up to 6 months post last dose
Other outcomes:
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:
citation: Bagarazzi ML, Yan J, Morrow MP, Shen X, Parker RL, Lee JC, Giffear M, Pankhong P, Khan AS, Broderick KE, Knott C, Lin F, Boyer JD, Draghia-Akli R, White CJ, Kim JJ, Weiner DB, Sardesai NY. Immunotherapy against HPV16/18 generates potent TH1 and cytotoxic cellular immune responses. Sci Transl Med. 2012 Oct 10;4(155):155ra138. doi: 10.1126/scitranslmed.3004414.
citation: Diehl MC, Lee JC, Daniels SE, Tebas P, Khan AS, Giffear M, Sardesai NY, Bagarazzi ML. Tolerability of intramuscular and intradermal delivery by CELLECTRA((R)) adaptive constant current electroporation device in healthy volunteers. Hum Vaccin Immunother. 2013 Oct;9(10):2246-52. doi: 10.4161/hv.24702. Epub 2013 Jun 4.