Clinical trial NCT02172911: A Study of INO-3112 DNA Vaccine With Electroporation in Participants With Cervical Cancer
Official title: Phase I/IIA, Open-Label, Safety, Tolerability, and Immunogenicity Study of INO-3112 Delivered by Electroporation (EP) in Women With Cervical Cancer After Chemoradiation for Newly Diagnosed Disease or Therapy for Recurrent and/or Persistent Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cervical Cancer
Keywords: Cervical cancer
Papillomavirus
Chemoradiation
Recurrent cervical cancer
Persistent cervical cancer
Lead sponsor: Inovio Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2014-06-24
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open-label study to evaluate the safety, tolerability, and immunogenicity of INO-3112 DNA vaccines delivered by electroporation (EP) to female participants with HPV-16 and/or 18-positive cervical carcinoma.

Detailed description: This is a Phase I/IIa, open-label study to evaluate the safety, tolerability, and immunogenicity of INO-3112 \[VGX-3100 and INO-9012\] delivered intramuscularly by electroporation in approximately 30 female participants with biopsy-proven, Stage IB-IVB inoperable invasive cervical carcinoma associated with HPV 16 and/or 18 who have completed treatment with standard chemoradiation therapy with curative intent (Cohort I) or in participants with persistent and/or recurrent cervical cancer associated with HPV 16 and/or 18 following salvage therapy (Cohort II).

Eligibility criteria: Inclusion Criteria:

1. Written informed consent.
2. Histological diagnosis of squamous cell carcinoma, adenocarcinoma or adenosquamous cell carcinoma of the cervix. Not accepted are small cell, clear cell and other rare variants of the classical adenocarcinoma.
3. Histologically confirmed, Stage IB-IVB, invasive cervical carcinoma associated with HPV 16 and/or 18 and meet the following eligibility criteria for either Cohort 1 or Cohort 2.

   1. Cohort 1

      * Newly diagnosed inoperable cervical cancer treated with chemoradiation therapy with curative intent and life expectancy of at least 12 months as assessed by the investigator
      * No CNS/spinal metastases
      * Able to initiate study treatment within 2 weeks of completion of last chemoradiation treatment
   2. Cohort 2

      * Persistent and/or recurrent cervical cancer
      * No CNS/spinal metastases
      * Able to initiate study treatment at least 2 weeks but no more than 4 weeks after completion of salvage therapy
      * Life expectancy of at least 12 months as assessed by the investigator
4. Electrocardiogram (ECG) with no clinically significant findings.
5. Chemistry, liver function tests, renal function, total CPK and hematology lab results must be ≤ Grade 1 at the time of screening.
6. Eastern Cooperative Oncology Group (ECOG) Performance status of ≤ 1.
7. Adequate venous access for repeated blood sampling according to the study schedule.
8. Women of child-bearing potential must have a negative serum pregnancy test and agree to remain sexually abstinent, have a partner who is sterile (i.e., vasectomy), or use two medically effective methods of contraception (e.g., oral contraception, barrier methods, spermicide, intrauterine device \[IUD\]).
9. Able and willing to comply with all study procedures.

Exclusion Criteria:

1. Pregnancy or breastfeeding.
2. History of previous therapeutic HPV vaccination.
3. Prior exposure to an investigational agent or device within 30 days of signing the ICF. Of note, the participant may participate in observational studies.
4. Positive serological test for HIV, Hep B or Hep C or history of HIV infection, Hepatitis B or Hepatitis C (women with cured HCV will be allowed; participant must have had a serologic test performed within 12 months of informed consent).
5. Prior major surgery from which the participant has not yet recovered to baseline.
6. High medical risks because of non-malignant systemic disease or with active uncontrolled infection.
7. Current malignancies at other sites, with the exception of adequately treated basal or squamous cell carcinoma of the skin.
8. Congestive heart failure or prior history of New York Heart Association (NYHA) class III/ IV cardiac disease.
9. Use of topical corticosteroids at or near the intended administration site.
10. Any cardiac pre-excitation syndromes (such as Wolff-Parkinson-White).
11. History of seizures (unless seizure free for 5 years).
12. Tattoos or scars within 2 cm of the intended site of injection or if there is implanted metal within the same limb. Any device implanted in the chest (e.g., cardiac pacemaker or defibrillator) excludes the use of the deltoid muscle on the same side of the body.
13. Active drug or alcohol use or dependence.
14. Imprisonment or compulsory detainment for treatment of either a psychiatric or physical (i.e. infectious disease) illness.
15. History of immunosuppressive or autoimmune disease.
16. Any other illnesses or conditions that in the opinion of the investigator may affect the safety of the participant or limit the evaluation of a participant or any study endpoint.

Primary outcomes:
measure: Percentage of Participants With at Least 1 Treatment Emergent Adverse Event (TEAE)
timeFrame: Up to 36 weeks
measure: Percentage of Participants With Grade 3 or Higher TEAEs Graded Per Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE, v 4.03)
timeFrame: Up to 36 weeks
measure: Percentage of Participants With Injection Site Reactions
timeFrame: Up to 36 weeks
measure: Rates of Acute Gastrointestinal, Genitourinary, or Other Chemoradiation Side Effects Above the Expected, Graded Per Acute Radiation Morbidity Scoring Criteria
timeFrame: Up to 36 weeks
measure: Change From Baseline in Hematocrit at the Indicated Time Points
timeFrame: Baseline and Week 4, 8,12,16,24, 32 and 48
measure: Change From Baseline in Hemoglobin at the Indicated Time Points
timeFrame: Baseline and Weeks 4, 8,12,16,24, 32 and 48
measure: Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points
timeFrame: Baseline and Weeks 4, 8,12,16,24, 32 and 48
measure: Change From Baseline in Platelet Count at the Indicated Time Points
timeFrame: Baseline and Weeks 4,8,12,16,24,32 and 48
measure: Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points
timeFrame: Baseline and Weeks 4 and 8
measure: Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points
timeFrame: Baseline and Weeks 4,8,12 and 16
measure: Change From Baseline in Bicarbonate, Glucose, Blood Urea Nitrogen (BUN), Calcium (Ca), Chloride (Cl), Potassium (K), Magnesium (Mg) and Sodium (Na) at the Indicated Time Points
timeFrame: Baseline and Weeks 4,8,12 and 16
measure: Change From Baseline in Albumin and Total Protein at the Indicated Time Points
timeFrame: Baseline and Weeks 4,8,12 and 16
measure: Change From Baseline in Creatine Phosphokinase (CPK) at the Indicated Time Points
timeFrame: Baseline and Week 16
measure: Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points
timeFrame: Baseline and Weeks 4, 8,12 and 16
Secondary outcomes:
measure: Change From Baseline in the Combined HPV-16 and HPV-18 E6 and E7 Antigen Specific Spot-Forming Units Per Million Peripheral Blood Mononuclear Cell (SFU/10^6 PBMC)
timeFrame: Baseline and Weeks 2, 4, 6, 8, 10,12,14,16, 24, 32, 36, 40 and 48
measure: E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA)
timeFrame: Baseline and Weeks 2, 4, 6, 8, 10,12,14,16, 24, 32, 36, 40 and 48
measure: E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA
timeFrame: Baseline and Weeks 2, 4, 6, 8, 10, 12, 14, 16, 24, 32, 36, 40 and 48
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
Study officials:
affiliation: Inovio Pharmaceuticals
name: Jeffrey Skolnik, MD
role: STUDY_DIRECTOR
References:
citation: 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.
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((R)) 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.