Safety Study of HPV DNA Vaccine to Treat Head and Neck Cancer Patients

Study Overview
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Brief Summary
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This study will test the safety of an HPV DNA vaccine after it is injected into your muscle using an electroporation device (TriGridTM Delivery System made by Ichor Medical Systems), and will test the ability of the vaccine to help your body's immune system to recognize HPV-infected and associated cancer cells. In addition to giving the vaccine using an electroporation device, we are giving the vaccine in combination with an immunomodulatory agent to further enhance immune responses against HPV-infected and associated cancer cells.

Official Title
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A Phase I Clinical Trial Assessing the Safety and Feasibility of Administration of pNGVL4a-CRT/E7(Detox) DNA Vaccine Using the Intramuscular TriGridTM Delivery System in Combination With Cyclophosphamide in HPV-16 Associated Head and Neck Cancer Patients

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Biological: DNA Vaccine
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed diagnosis of squamous cell carcinoma of the head and neck or unknown primary with level II/III (jugulodigastric) nodal involvement (which have been found in previous studies to be the result of subclinical oropharyngeal carcinoma). Head and neck cancer patients documented to have HPV-16 DNA within their tumors as determined by in situ hybridization are eligible for this study. Fresh-frozen or paraffin-embedded material must be available for in situ hybridization testing for HPV-16 DNA. Staging criteria established by the American Joint Committee on Clinical Investigation (AJCC, Fifth Edition, 1997) for Stage III (T1-3N1M0, T3N0M0) or IV (T1-4N2M0, T4N0-1M0 ) disease. Age ≥ 18 years Life expectancy of greater than 4 months. Baseline Eastern Cooperative Oncology Group performance status of 0, 1 at the time of multi-modality treatment administration. 9. Patients must have adequate organ function at the time of enrollment as defined by the following parameters: white blood cell count > 3,000 lymphocyte number > 500 absolute neutrophil count > 1,000 platelets > 90,000 hemoglobulin > 9 total bilirubin <3 X the institutional limit of normal AST(SGOT)/ALT(SGPT) <3 X the institutional limit of normal creatinine < 2.5X the institutional limit of normal Exclusion Criteria: Diagnosis of immunosuppression or prolonged, active use of immunosuppressive medications such as steroids. Prior enrollment in any vaccine study in the past 24 months. Presence of uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements. Presence or history of autoimmune disease such as multiple sclerosis, exclusive of a history of thyroiditis, psoriasis, inflammatory bowel disease, or Sjogren's syndrome. Pregnancy or breast feeding. Pregnancy is defined as any female subject of reproductive potential [defined as girls who have reached menarche or women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or have not undergone surgical sterilization (e.g., hysterectomy, bilateral oophorectomy, or bilateral tubal ligation)] must have a negative serum -hcg test within 3 days prior to study entry. History of prior malignancy permitted if patient has been disease free for ≥ 5 years, however individuals with completely resected basal cell or squamous cell carcinoma of the skin within this interval may be enrolled. Inability to understand or unwillingness to sign an informed consent document. Patients with a history of arterial or venous thrombosis. Patients with non-healed wounds. Patients with chronic infection with or a history of Hepatitis B, Hepatitis C, or HIV infection as determined by serology tests obtained during the eligibility screening. Current use of any electronic stimulation device, such as cardiac demand pacemakers, automatic implantable cardiac defibrillator, nerve stimulators, or deep brain stimulators. History of, or documented in an EKG within 30 days of study eligibility screening, cardiac arrhythmia or palpitations [e.g., supraventricular tachycardia, atrial fibrillation, frequent ectopy, or sinus bradycardia (i.e., <50 beats per minute on exam)] prior to study entry. NOTE: Sinus arrhythmia is not excluded. History of syncope or fainting episode within 1 year of study entry. Seizure disorder or any history of prior seizure. Presence of any surgical or traumatic metal implants at the site of administration (deltoid muscles). Bleeding disorder or other contraindication for intramuscular injection. A skin-fold measurement of the cutaneous and subcutaneous tissue that exceeds 40mm at one or more of the eligible injection sites (the medial deltoid muscles). History of axillary lymph node dissection. Patients who have had chemotherapy or radiotherapy within 28 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 28 days earlier.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 - DNA Vaccine (Dose 0.5 mg/dose)<br>pNGVL-4a-CRT/E7 (detox) DNA Vaccine (Dose 0.5 mg/dose) + Cyclophosphamide (200 mg/m2) | Biological: DNA Vaccine<br>* Patients will receive intramuscular needle injections of pNGVL4a-CRT/E7 (detox) DNA vaccine using the TDS-IM device on Day 1, 22, and 43 for a total of three vaccinations per patient. One day prior to each DNA vaccination, the patient will receive a single low dose of 200 mg/m2 of cyclophosphamide intravenously. The DNA vaccine will be administered in a dose-escalating manner.<br>* Other names: pNGVL-4a-CRT/E7 (detox) DNA Vaccine;Drug: Cyclophosphamide<br>* A single low dose of 200 mg/m2 of cyclophosphamide (CTX) will be administered intravenously up to 24 hours (Day 0) prior to each DNA vaccination.<br>* Other names: Cytoxan;|
| Experimental: Cohort 2 - DNA Vaccine (Dose 1.0 mg/dose)<br>pNGVL-4a-CRT/E7 (detox) DNA Vaccine (Dose 1.0 mg/dose) + Cyclophosphamide (200 mg/m2) | Biological: DNA Vaccine<br>* Patients will receive intramuscular needle injections of pNGVL4a-CRT/E7 (detox) DNA vaccine using the TDS-IM device on Day 1, 22, and 43 for a total of three vaccinations per patient. One day prior to each DNA vaccination, the patient will receive a single low dose of 200 mg/m2 of cyclophosphamide intravenously. The DNA vaccine will be administered in a dose-escalating manner.<br>* Other names: pNGVL-4a-CRT/E7 (detox) DNA Vaccine;Drug: Cyclophosphamide<br>* A single low dose of 200 mg/m2 of cyclophosphamide (CTX) will be administered intravenously up to 24 hours (Day 0) prior to each DNA vaccination.<br>* Other names: Cytoxan;|
| Experimental: Cohort 3 - DNA Vaccine (Dose 2.0 mg/dose)<br>pNGVL-4a-CRT/E7 (detox) DNA Vaccine (Dose 2.0 mg/dose) + Cyclophosphamide (200 mg/m2) | Biological: DNA Vaccine<br>* Patients will receive intramuscular needle injections of pNGVL4a-CRT/E7 (detox) DNA vaccine using the TDS-IM device on Day 1, 22, and 43 for a total of three vaccinations per patient. One day prior to each DNA vaccination, the patient will receive a single low dose of 200 mg/m2 of cyclophosphamide intravenously. The DNA vaccine will be administered in a dose-escalating manner.<br>* Other names: pNGVL-4a-CRT/E7 (detox) DNA Vaccine;Drug: Cyclophosphamide<br>* A single low dose of 200 mg/m2 of cyclophosphamide (CTX) will be administered intravenously up to 24 hours (Day 0) prior to each DNA vaccination.<br>* Other names: Cytoxan;|
| Experimental: Cohort 4 - DNA Vaccine (Dose 4.0 mg/dose)<br>pNGVL-4a-CRT/E7 (detox) DNA Vaccine (Dose 4.0 mg/dose) + Cyclophosphamide (200 mg/m2) | Biological: DNA Vaccine<br>* Patients will receive intramuscular needle injections of pNGVL4a-CRT/E7 (detox) DNA vaccine using the TDS-IM device on Day 1, 22, and 43 for a total of three vaccinations per patient. One day prior to each DNA vaccination, the patient will receive a single low dose of 200 mg/m2 of cyclophosphamide intravenously. The DNA vaccine will be administered in a dose-escalating manner.<br>* Other names: pNGVL-4a-CRT/E7 (detox) DNA Vaccine;Drug: Cyclophosphamide<br>* A single low dose of 200 mg/m2 of cyclophosphamide (CTX) will be administered intravenously up to 24 hours (Day 0) prior to each DNA vaccination.<br>* Other names: Cytoxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events after administration of pNGVL4a-CRT/E7 (detox) DNA vaccine using the intramuscular TriGridTM Delivery System (TDS-IM) in combination with cyclophosphamide |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with measurable HPV-specific immune responses after vaccination |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV, Head and Neck Cancer, Vaccine, Immunotherapy, Cyclophosphamide, Sexually Transmitted Diseases, Viral