Clinical Trials /

A Study of INO-3112 DNA Vaccine With Electroporation in Participants With Cervical Cancer

NCT02172911

Description:

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.

Related Conditions:
  • Cervical Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: HPV-004
  • NCT ID: NCT02172911

Conditions

  • Cervical Cancer

Interventions

DrugSynonymsArms
INO-3112VGX-3100, INO-9012Cohort I: INO-3112: Curative Intent

Purpose

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).
    

Trial Arms

NameTypeDescriptionInterventions
Cohort I: INO-3112: Curative IntentExperimentalCohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.
  • INO-3112
Cohort II: INO-3112: Salvage TherapyExperimentalCohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.
  • INO-3112

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants With at Least 1 Treatment Emergent Adverse Event (TEAE)
Time Frame:Up to 36 weeks
Safety Issue:
Description:An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can include any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after the first dose of study drug.

Secondary Outcome Measures

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)
Time Frame:Baseline and Weeks 2, 4, 6, 8, 10,12,14,16, 24, 32, 36, 40 and 48
Safety Issue:
Description:Whole blood and serum samples to be tested for antibodies to the human papillomavirus (HPV) E6 and E7 proteins and/or T-lymphocytes producing interferon-gamma (IFN-γ) elicited by INO-3112 were assessed by enzyme-linked immunosorbent spot-forming assay (ELISpot).
Measure:E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA)
Time Frame:Baseline and Weeks 2, 4, 6, 8, 10,12,14,16, 24, 32, 36, 40 and 48
Safety Issue:
Description:Antigen-specific humoral responses against HPV E6 and E7 antigens induced by INO-3112 were measured using ELISA. Commercially available recombinant human HPV-16 and HPV-18 proteins were used to assess the induction of binding antibodies to each of the antigen components.
Measure:E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA
Time Frame:Baseline and Weeks 2, 4, 6, 8, 10, 12, 14, 16, 24, 32, 36, 40 and 48
Safety Issue:
Description:Antigen-specific humoral responses against HPV E6 and E7 antigens induced by INO-3112 were measured using ELISA. Commercially available recombinant human HPV-16 and HPV-18 proteins were used to assess the induction of binding antibodies to each of the antigen components.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Inovio Pharmaceuticals

Trial Keywords

  • Cervical cancer
  • Papillomavirus
  • Chemoradiation
  • Recurrent cervical cancer
  • Persistent cervical cancer

Last Updated

February 21, 2021