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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 5
- 主要终点
- Rates of Acute Gastrointestinal, Genitourinary, or Other Chemoradiation Side Effects Above the Expected, Graded Per Acute Radiation Morbidity Scoring Criteria
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Written informed consent.
- •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.
- •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
- •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
- •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
- •Electrocardiogram (ECG) with no clinically significant findings.
- •Chemistry, liver function tests, renal function, total CPK and hematology lab results must be ≤ Grade 1 at the time of screening.
- •Eastern Cooperative Oncology Group (ECOG) Performance status of ≤
- •Adequate venous access for repeated blood sampling according to the study schedule.
- •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]).
- •Able and willing to comply with all study procedures.
排除标准
- •Pregnancy or breastfeeding.
- •History of previous therapeutic HPV vaccination.
- •Prior exposure to an investigational agent or device within 30 days of signing the ICF. Of note, the participant may participate in observational studies.
- •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).
- •Prior major surgery from which the participant has not yet recovered to baseline.
- •High medical risks because of non-malignant systemic disease or with active uncontrolled infection.
- •Current malignancies at other sites, with the exception of adequately treated basal or squamous cell carcinoma of the skin.
- •Congestive heart failure or prior history of New York Heart Association (NYHA) class III/ IV cardiac disease.
- •Use of topical corticosteroids at or near the intended administration site.
- •Any cardiac pre-excitation syndromes (such as Wolff-Parkinson-White).
- •History of seizures (unless seizure free for 5 years).
- •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.
- •Active drug or alcohol use or dependence.
- •Imprisonment or compulsory detainment for treatment of either a psychiatric or physical (i.e. infectious disease) illness.
- •History of immunosuppressive or autoimmune disease.
- •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.
结局指标
主要结局
Rates of Acute Gastrointestinal, Genitourinary, or Other Chemoradiation Side Effects Above the Expected, Graded Per Acute Radiation Morbidity Scoring Criteria
时间窗: Up to 36 weeks
Change From Baseline in Hemoglobin at the Indicated Time Points
时间窗: Baseline and Weeks 4, 8,12,16,24, 32 and 48
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.
Change From Baseline in Platelet Count at the Indicated Time Points
时间窗: Baseline and Weeks 4,8,12,16,24,32 and 48
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.
Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points
时间窗: Baseline and Weeks 4,8,12 and 16
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).
Change From Baseline in Albumin and Total Protein at the Indicated Time Points
时间窗: Baseline and Weeks 4,8,12 and 16
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.
Percentage of Participants With Grade 3 or Higher TEAEs Graded Per Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE, v 4.03)
时间窗: Up to 36 weeks
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.
Change From Baseline in Hematocrit at the Indicated Time Points
时间窗: Baseline and Week 4, 8,12,16,24, 32 and 48
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.
Percentage of Participants With at Least 1 Treatment Emergent Adverse Event (TEAE)
时间窗: Up to 36 weeks
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.
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
时间窗: Baseline and Weeks 4,8,12 and 16
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.
Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points
时间窗: Baseline and Weeks 4 and 8
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.
Percentage of Participants With Injection Site Reactions
时间窗: Up to 36 weeks
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.
Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points
时间窗: Baseline and Weeks 4, 8,12,16,24, 32 and 48
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).
Change From Baseline in Creatine Phosphokinase (CPK) at the Indicated Time Points
时间窗: Baseline and Week 16
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.
Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points
时间窗: Baseline and Weeks 4, 8,12 and 16
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.
次要结局
- E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA)(Baseline and Weeks 2, 4, 6, 8, 10,12,14,16, 24, 32, 36, 40 and 48)
- 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)(Baseline and Weeks 2, 4, 6, 8, 10,12,14,16, 24, 32, 36, 40 and 48)
- E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA(Baseline and Weeks 2, 4, 6, 8, 10, 12, 14, 16, 24, 32, 36, 40 and 48)