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

November 20, 2018 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

2

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. 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).
  2. 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.
  3. Fresh-frozen or paraffin-embedded material must be available for in situ hybridization testing for HPV-16 DNA.
  4. 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.
  5. Age ≥ 18 years
  6. Life expectancy of greater than 4 months.
  7. 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:

  1. Diagnosis of immunosuppression or prolonged, active use of immunosuppressive medications such as steroids.
  2. Prior enrollment in any vaccine study in the past 24 months.
  3. 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.
  4. Presence or history of autoimmune disease such as multiple sclerosis, exclusive of a history of thyroiditis, psoriasis, inflammatory bowel disease, or Sjogren's syndrome.
  5. 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.
  6. 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.
  7. Inability to understand or unwillingness to sign an informed consent document.
  8. Patients with a history of arterial or venous thrombosis.
  9. Patients with non-healed wounds.
  10. 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.
  11. Current use of any electronic stimulation device, such as cardiac demand pacemakers, automatic implantable cardiac defibrillator, nerve stimulators, or deep brain stimulators.

  12. 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.

  13. History of syncope or fainting episode within 1 year of study entry.
  14. Seizure disorder or any history of prior seizure.
  15. Presence of any surgical or traumatic metal implants at the site of administration (deltoid muscles).
  16. Bleeding disorder or other contraindication for intramuscular injection.
  17. 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).
  18. History of axillary lymph node dissection.
  19. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional 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)
pNGVL-4a-CRT/E7 (detox) DNA Vaccine (Dose 0.5 mg/dose) + Cyclophosphamide (200 mg/m2)
Biological: DNA Vaccine
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.
Other Names:
  • pNGVL-4a-CRT/E7 (detox) DNA Vaccine
Drug: Cyclophosphamide
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.
Other Names:
  • Cytoxan
Experimental: Cohort 2 - DNA Vaccine (Dose 1.0 mg/dose)
pNGVL-4a-CRT/E7 (detox) DNA Vaccine (Dose 1.0 mg/dose) + Cyclophosphamide (200 mg/m2)
Biological: DNA Vaccine
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.
Other Names:
  • pNGVL-4a-CRT/E7 (detox) DNA Vaccine
Drug: Cyclophosphamide
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.
Other Names:
  • Cytoxan
Experimental: Cohort 3 - DNA Vaccine (Dose 2.0 mg/dose)
pNGVL-4a-CRT/E7 (detox) DNA Vaccine (Dose 2.0 mg/dose) + Cyclophosphamide (200 mg/m2)
Biological: DNA Vaccine
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.
Other Names:
  • pNGVL-4a-CRT/E7 (detox) DNA Vaccine
Drug: Cyclophosphamide
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.
Other Names:
  • Cytoxan
Experimental: Cohort 4 - DNA Vaccine (Dose 4.0 mg/dose)
pNGVL-4a-CRT/E7 (detox) DNA Vaccine (Dose 4.0 mg/dose) + Cyclophosphamide (200 mg/m2)
Biological: DNA Vaccine
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.
Other Names:
  • pNGVL-4a-CRT/E7 (detox) DNA Vaccine
Drug: Cyclophosphamide
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.
Other Names:
  • Cytoxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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
Time Frame: 5 years
5 years

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

National Institute of Dental and Craniofacial Research (NIDCR)
Ichor Medical Systems Incorporated

Investigators

  • Principal Investigator: Joseph Califano, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2012

Primary Completion (Actual)

October 1, 2015

Study Completion (Actual)

October 1, 2015

Study Registration Dates

First Submitted

November 21, 2011

First Submitted That Met QC Criteria

December 13, 2011

First Posted (Estimate)

December 15, 2011

Study Record Updates

Last Update Posted (Actual)

November 23, 2018

Last Update Submitted That Met QC Criteria

November 20, 2018

Last Verified

November 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • J11129
  • P50DE019032 (U.S. NIH Grant/Contract)
  • NA_00023916 (Other Identifier: JHMIRB)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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