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

This study has been terminated.
(Study Funding Terminated)
Sponsor:
Collaborators:
Ichor Medical Systems Incorporated
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01493154
First received: November 21, 2011
Last updated: September 5, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Biological: DNA Vaccine
Drug: Cyclophosphamide
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of participants with measurable HPV-specific immune responses after vaccination [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Enrollment: 2
Study Start Date: April 2012
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Cytoxan

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01493154

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Ichor Medical Systems Incorporated
Investigators
Principal Investigator: Joseph Califano, MD Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital
  More Information

Additional Information:
Publications:
Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01493154     History of Changes
Other Study ID Numbers: J11129, P50DE019032, NA_00023916
Study First Received: November 21, 2011
Last Updated: September 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
HPV
Head and Neck Cancer
Vaccine
Immunotherapy
Cyclophosphamide
Sexually Transmitted Diseases, Viral

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 22, 2014