Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Uterine Cervical Neoplasms

Recurrence

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

All Drugs and Chemicals

Vaccines

Cohort 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.

Cohort 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.

1.1 mL intramuscular (IM) injection of INO-3112 (VGX-3100 + INO-9012) was administered followed immediately by electroporation (EP) with CELLECTRA™-5P on Day 0, Week 4, Week 8, and Week 12.

INO-3112

CELLECTRA™-5P was used for EP following IM delivery of INO-3112 on Day 0, Week 4, Week 8, and Week 12.

CELLECTRA™-5P

Jeffrey Skolnik, MD

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.

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).

Only female participants with biopsy-proven, Stage IB-IVB inoperable invasive cervical carcinoma associated with HPV-16 and/or HPV-18 were included.

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

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

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.

An 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. The severity of TEAEs was assessed by the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE,v 4.03). TEAEs were graded on a 5-point scale where 1 = Mild, 2 = Moderate, 3 = Severe, 4 = Potentially life-threatening and 5 = Death.

Injection site reactions and administration site pain were evaluated starting 30 minutes following injection/EP. Injection site reactions were assessed in accordance with the 'Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials' (Food and Drug Administration \[FDA\] Guidance for Industry, September 2007). Local reaction to the injectable product such as pain, tenderness, erythema/redness and induration/swelling were graded on a 4-point scale where: 1 = Mild, 2 = Moderate, 3 = Severe and 4 = Potentially life-threatening.

Clinical laboratory parameters (hematology, serum chemistry, and creatine phosphokinase \[CPK\]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.

Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase \[CPK\]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.

Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase \[CPK\]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit. Hematology parameters analyzed for this outcome measure included: white blood cell (WBC) count, count of lymphocytes (L), monocytes (M) and neutrophils (N).

Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase \[CPK\]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit. Clinical chemistry parameter assessed in this outcome measure included alkaline phosphatase (ALP), alanine amino transferase (ALT) and aspartate amino transferase (AST).

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).

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.

Inovio Pharmaceuticals

Cohort I: INO-3112: Curative Intent

Cohort II: INO-3112: Salvage Therapy

Total

Age, Continuous

Female

Sex/Gender, Customized

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Study Director

Safety population included all participants who received at least one dose of study treatment plus EP.

Percentage of Participants With at Least 1 Treatment Emergent Adverse Event (TEAE)

Anaemia

Disseminated Intravascular Coagulation

Abdominal Pain

Intestinal Perforation

Pneumonia

Pathological Fracture

Percentage of Participants With Grade 3 or Higher TEAEs Graded Per Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE, v 4.03)

Injection Site Bruising

Injection Site Discolouration

Injection Site Erythema

Injection Site Haemorrhage

Injection Site Pain

Injection Site Swelling

Percentage of Participants With Injection Site Reactions

The above-mentioned outcome could not be assessed as no data were captured that reflect the expected rates of acute gastrointestinal, genitourinary or other chemoradiation side effects, in order to compare those collected on this study with those from prior studies. While adverse event data related to study therapy were captured, these were not graded per acute radiation morbidity score because of the above-noted limitation. No comparison was thus possible that would reflect rates expected.

Rates of Acute Gastrointestinal, Genitourinary, or Other Chemoradiation Side Effects Above the Expected, Graded Per Acute Radiation Morbidity Scoring Criteria

Baseline

Change from Baseline at Week 4

Change from Baseline at Week 8

Change from Baseline at Week 12

Change from Baseline at Week 16

Change from Baseline at Week 24

Change from Baseline at Week 32

Change from Baseline at Week 48

Safety population included all participants who received at least one dose of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point.

Change From Baseline in Hematocrit at the Indicated Time Points

The safety population included all participants who received at least one dose of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point.

Change From Baseline in Hemoglobin at the Indicated Time Points

L, Baseline

L,Change from Baseline at Week 4

L,Change from Baseline at Week 8

L, Change from Baseline at Week 12

L, Change from Baseline at Week 16

L, Change From Baseline at Week 24

L, Change from Baseline at Week 32

L, Change from Baseline at Week 48

M, Baseline

M,Change from Baseline at Week 4

M,Change from Baseline at Week 8

M,Change from Baseline at Week 12

M,Change from Baseline at Week 16

M,Change from Baseline at Week 24

M,Change from Baseline at Week 32

M,Change from Baseline at Week 48

N, Baseline

N,Change from Baseline at Week 4

N,Change from Baseline at Week 8

N,Change from Baseline at Week 12

N,Change from Baseline at Week 16

N,Change from Baseline at Week 24

N,Change from Baseline at Week 32

N,Change from Baseline at Week 48

WBC, Baseline

WBC, Change from Baseline at Week 4

WBC, Change from Baseline at Week 8

WBC, Change from Baseline at Week 12

WBC, Change from Baseline at Week 16

WBC, Change from Baseline at Week 24

WBC, Change from Baseline at Week 32

WBC, Change from Baseline at Week 48

Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points

Platelet Count, Baseline

Platelet Count, Change from Baseline at Week 4

Platelet Count, Change from Baseline at Week 8

Platelet Count, Change from Baseline at Week 12

Platelet Count, Change from Baseline at Week 16

Platelet Count, Change From Baseline at Week 24

Platelet Count, Change from Baseline at Week 32

Platelet Count, Change from Baseline at Week 48

Change From Baseline in Platelet Count at the Indicated Time Points

RBC Count, Baseline

RBC Count, Change from Baseline at Week 4

RBC Count, Change from Baseline at Week 8

Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points

ALP, Baseline

ALP, Change from Baseline at Week 4

ALP, Change from Baseline at Week 8

ALP, Change from Baseline at Week 12

ALP, Change from Baseline at Week 16

ALT, Baseline

ALT, Change from Baseline at Week 4

ALT, Change from Baseline at Week 8

ALT, Change from Baseline at Week 12

ALT, Change from Baseline at Week 16

AST, Baseline

AST, Change from Baseline at Week 4

AST, Change from Baseline at Week 8

AST, Change from Baseline at Week 12

AST, Change from Baseline at Week 16

Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points

Bicarbonate, Baseline

Bicarbonate, Change from Baseline at Week 4

Bicarbonate, Change from Baseline at Week 8

Bicarbonate, Change from Baseline at Week 12

Bicarbonate, Change from Baseline at Week 16

Glucose, Baseline

Glucose, Change from Baseline at Week 4

Glucose, Change from Baseline at Week 8

Glucose, Change from Baseline at Week 12

Glucose, Change from Baseline at Week 16

BUN, Baseline

BUN, Change from Baseline at Week 4

BUN, Change from Baseline at Week 8

BUN, Change from Baseline at Week 12

BUN, Change from Baseline at Week 16

Ca, Baseline

Ca, Change from Baseline at Week 4

Ca, Change from Baseline at Week 8

Ca, Change from Baseline at Week 12

Ca, Change from Baseline at Week 16

Cl, Baseline

Cl, Change from Baseline at Week 4

Cl, Change from Baseline at Week 8

Cl, Change from Baseline at Week 12

Cl, Change from Baseline at Week 16

K, Baseline

K, Change from Baseline at Week 4

K, Change from Baseline at Week 8

K, Change from Baseline at Week 12

K, Change from Baseline at Week 16

Mg, Baseline

Na, Baseline

Na, Change from Baseline at Week 4

Na, Change from Baseline at Week 8

Na, Change from Baseline at Week 12

Na, Change from Baseline at Week 16

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

Albumin, Baseline

Albumin, Change from Baseline at Week 4

Albumin, Change from Baseline at Week 8

Albumin, Change from Baseline at Week 12

Albumin, Change from Baseline at Week 16

Total protein, Baseline

Total protein, Change from Baseline at Week 4

Total protein, Change from Baseline at Week 8

Total protein, Change from Baseline at Week 12

Total protein, Change from Baseline at Week 16

Change From Baseline in Albumin and Total Protein at the Indicated Time Points

CPK, Baseline

CPK, Change from Baseline at Week 16

Change From Baseline in Creatine Phosphokinase (CPK) at the Indicated Time Points

Creatinine, Baseline

Creatinine, Change from Baseline at Week 4

Creatinine, Change from Baseline at Week 8

Creatinine, Change from Baseline at Week 12

Creatinine, Change from Baseline at Week 16

Total Bilirubin, Baseline

Total Bilirubin, Change from Baseline at Week 4

Total Bilirubin, Change from Baseline at Week 8

Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points

Spots Global Cancer Trial Database for A Study of INO-3112 DNA Vaccine With Electroporation in Participants With Cervical Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial