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

Study Description

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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 to subjects with HPV associated head and neck squamous cell cancer.

Condition or disease	Intervention/treatment	Phase
Head and Neck Squamous Cell Cancer	Biological: 1.1 mL of INO-3112 (VGX-3100 + INO-9012) delivered IM via EP with CELLECTRA-5P device	Phase 1; Phase 2

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) subjects with HPV positive head and neck cancer. The immunotherapy will be studied in following two groups of subjects:

1. Subjects who will receive immunotherapy before and after definitive surgery (Cohort I)
2. Subjects who will receive immunotherapy at least 2 months after chemoradiation therapy (Cohort II).

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	22 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Prospective Study of HPV Specific Immunotherapy in Patients With HPV Associated Head and Neck Squamous Cell Carcinoma (HNSCCa)
Study Start Date :	June 2014
Actual Primary Completion Date :	January 2017
Actual Study Completion Date :	November 2017

Arms and Interventions

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Arm	Intervention/treatment
Surgery Cohort; 1.1 mL of INO-3112 (VGX-3100 and INO-9012) delivered IM via CELLECTRA-5P device	Biological: 1.1 mL of INO-3112 (VGX-3100 + INO-9012) delivered IM via EP with CELLECTRA-5P device; Eligible subjects who consent to participate in the study will receive a 1.1 mL IM injection of INO-3112 (VGX-3100 and INO-9012) via IM+EP with CELLECTRA®-5P. All subjects will receive a total of 4 doses of immunotherapy; Other Names: VGX-3100; INO-9012
Chemoradiation; 1.1 mL of INO-3112 (VGX-3100 and INO-9012) delivered IM via CELLECTRA-5P device	Biological: 1.1 mL of INO-3112 (VGX-3100 + INO-9012) delivered IM via EP with CELLECTRA-5P device; Eligible subjects who consent to participate in the study will receive a 1.1 mL IM injection of INO-3112 (VGX-3100 and INO-9012) via IM+EP with CELLECTRA®-5P. All subjects will receive a total of 4 doses of immunotherapy; Other Names: VGX-3100; INO-9012

Outcome Measures

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Primary Outcome Measures :

1. Safety and Tolerability of INO-3112 (VGX-3100 and INO-9012) delivered via IM+EP [ Time Frame: 6 months post last dose ]

   Evaluate the safety and tolerability of immunotherapy with INO-3112 (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 will be measured

Secondary Outcome Measures :

1. Immunogenicity of INO-3112 (VGX-3100 and INO-9012) delivered via IM+EP [ Time Frame: 6 months post last dose ]

   Evaluate the cellular and humoral immune responses to immunotherapy with INO-3112 (VGX-3100 and INO-9012) delivered by electroporation with CELLECTRA®-5P in patients with HPV associated Head and Neck cancer

   Measure HPV 16 and HPV 18 E6 E7 Ig levels, IFN-γ-secreting cells and cytotoxic T cells in response to HPV specific immunotherapy.

Other Outcome Measures:

1. Anti-tumor effects [ Time Frame: 6 months post last dose ]
   Anti-tumor effects by investigator's clinical assessment
2. Progression Free Survival [ Time Frame: 6 months post last dose ]
   Progression Free Survival

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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 subjects, p16 positivity must be confimed prior to first dose
   • For subjects post-chemoradiation, HPV 16 and HPV 18 positivity must be confirmed prior to 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), AST, ALT within 2.5x institutional ULN, 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.

Contacts and Locations

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Locations

United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Inovio Pharmaceuticals

University of Pennsylvania

Investigators

Study Director:	Ildiko Csiki, MD	Inovio Pharmaceuticals

More Information

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Additional Information:

Sponsor's Website 

Publications:

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.

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.

Responsible Party:	Inovio Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT02163057 History of Changes
Other Study ID Numbers:	HPV-005
First Posted:	June 13, 2014
Last Update Posted:	March 7, 2018
Last Verified:	March 2018

Keywords provided by Inovio Pharmaceuticals:

Head and neck squamous cell cancer; Papillomavirus

Additional relevant MeSH terms:

Carcinoma, Squamous Cell; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma	Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site