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

Head and Neck Squamous Cell Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02163057
• Other study ID #: HPV-005
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 13, 2014
• Est. completion date: January 23, 2017

Study information

• Verified date: January 2021
• Source: Inovio Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: January 23, 2017
• Est. primary completion date: January 23, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Head and Neck Squamous Cell Cancer
• Neoplasms, Squamous Cell
• Squamous Cell Carcinoma of Head and Neck

Intervention

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.

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

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Inovio Pharmaceuticals	University of Pennsylvania

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View 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(®) 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Event (SAEs)	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.	Up to 6 months post last dose
Secondary	E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA)	Titers for HPV-16 and HPV-18 E6- and E7-specific antibodies were assessed by ELISA.	Up to 6 months post last dose
Secondary	E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA	Titers for HPV-16 and HPV-18 E6- and E7-specific antibodies were assessed by ELISA.	Up to 6 months post last dose
Secondary	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)		Baseline up to 6 months post last dose
Secondary	Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-16 as Assessed by Flow Cytometry	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.	At baseline and Week 2 post last dose
Secondary	Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-18 as Assessed by Flow Cytometry	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.	At baseline and Week 2 post last dose
Secondary	Mean Difference in Tumor Infiltrating Lymphocytes (TILs) in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC)	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.	At screening and post-surgery
Secondary	Mean Difference in CD8/FoxP3 Ratio in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC)	The difference in means (post-surgery minus screening) for the CD8/FoxP3 ratio was analyzed using immunohistochemistry staining techniques.	At screening and post-surgery
Secondary	Phenotype of Cultured TILs		Up to 6 months post last dose

External Links

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