NCT03603808已完成2 期
A Phase 2 Evaluation of VGX-3100, a Synthetic DNA Immunotherapy Targeting Human Papillomavirus 16 and 18 E6 and E7 Proteins, for Anal High-Grade Squamous Intraepithelial Lesions (HSIL) in HIV-Positive Individuals
AIDS Malignancy Consortium16 个研究点 分布在 2 个国家目标入组 44 人开始时间: 2018年9月21日最近更新:
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 44
- 试验地点
- 16
- 主要终点
- Overall response rate at 48 weeks
研究概览
简要总结
This phase II trial studies the use of human papillomavirus (HPV) deoxyribonucleic acid (DNA) plasmids therapeutic vaccine VGX-3100 (VGX-3100) and electroporation in treating patients with human immunodeficiency virus (HIV)-positive high-grade anal lesions. Vaccines made from DNA may help the body build an effective immune response to kill tumor cells. Electroporation helps pores in your body's cells take in the drug to strengthen your immune system's response. Giving VGX-3100 and electroporation together may work better in treating patients with high-grade anal lesions.
详细描述
PRIMARY OBJECTIVES:
I. To determine the proportion of participants with HPV-16 and/or HPV-18-positive anal high grade squamous intraepithelial neoplasia (HSIL) that achieve either complete or partial response (which is defined as histopathological regression from HSIL to low grade squamous intraepithelial neoplasia [LSIL] or normal) at 48 weeks after the first dose of VGX-3100 (VGX-3100).
SECONDARY OBJECTIVES:
I. To determine the safety and tolerability as assessed by Common Terminology Criteria for Adverse Events version 5 (CTCAE v5.0).
II. To determine the proportion of participants with HPV-16 and/or HPV-18-positive anal HSIL that achieve complete response (which is defined as histopathological regression from HSIL to normal) at 48 weeks after the first dose of VGX-3100.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Biopsy-proven intra-anal or per-HSIL at baseline (anal intraepithelial neoplasia [AIN]2 with a positive p16 stain, PAIN2-3, AIN2-3, or PAIN3/AIN3)
- •At least one focus of HSIL must be large enough to be monitored for response, i.e., not completely removed after the screening biopsy
- •Must be positive for HPV-16 or -18 on genotyping performed on screening anal swab
- •HIV positive; documentation of HIV-1 infection by means of any one of the following:
- •Documentation of HIV diagnosis in the medical record by a licensed health care provider
- •Any licensed HIV screening antibody and/or HIV antibody/antigen combination assay confirmed by a second licensed HIV assay such as a HIV-1 Western blot confirmation or HIV rapid multispot antibody differentiation assay; NOTE: A ?licensed? assay refers to a U.S. Food and Drug Administration (FDA)-approved assay, which is required for all investigational new drug (IND) studies
- •Must be documented to be on an effective combination antiretroviral therapy (ART) regimen, generally a 3-drug regimen based on Department of Health and Human Services (DHHS) treatment guidelines by a licensed health care provider; documentation may be a record of an ART prescription in the participant?s medical record, a written prescription in the name of the participant for ART, or pill bottles for ART with a label showing the participant?s name; each component agent of a multi-class combination ART regimen will be counted toward the 3-drug requirement
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
- •Life expectancy of greater than 5 years
- •Within 90 days before enrollment: Leukocytes: >= 3,000/mm^3
- •Within 90 days before enrollment: Absolute neutrophil count: >= 1,500/mm^3
- •Within 90 days before enrollment: Platelets: >= 100,000/mm^3
- •Within 90 days before enrollment: CD4 count >= 350 cells/mm^3
- •Within 90 days before enrollment: HIV plasma HIV-1 RNA below detected limit obtained by Food and Drug Administration (FDA)-approved assays (limit of detection: 75 copies/mL or less)
- •For females, must have cervical cytology and visual examination of the vulva, vagina, and cervix within 12 months prior to enrollment with confirmation of no evidence of carcinoma; for women who underwent hysterectomy with removal of the cervix, cytology from the vagina within 12 months is required
- •For women of child-bearing potential (WOCBP), they must have a negative serum or urine pregnancy test within 72 hours of receiving the first dose of VGX-3100 and be at least 3 months post-partum; WOCBP and men must agree to use adequate contraception (oral contraceptive pills, intrauterine device, Nexplanon, Depo-Provera, or permanent sterilization, etc., or another acceptable method as determined by the investigator) prior to study entry, for the duration of study participation, and 4 months after completion of VGX-3100 administration; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- •A WOCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
- •Men who could father a child must agree to use at least one form of birth control during or continued abstinence from heterosexual intercourse prior to the study, for the duration of study participation, and 4 months after completion of VGX-3100 administration
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Treatment or removal of HSIL less than 3 months prior to enrollment.
- •Patients who received any other investigational agents within the 4 weeks before enrollment, other than investigational antiretroviral agents for HIV and investigational agents for hepatitis C
- •Participants should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 2 weeks of study drug administration; inhaled steroids and adrenal replacement doses =< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease; participants are permitted to use ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption); physiologic replacement doses of systemic corticosteroids are permitted, even if >= 10 mg/day prednisone equivalents; a brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted; use of anabolic steroids is permitted; topical steroids are permitted as long as they are not directly applied to the area of the skin where electroporation is planned
- •History of anal cancer, penile, vulvar, vaginal, or cervical cancer, or signs of any of these malignancies at baseline; participants with prior carcinoma in situ will not be considered to have prior cancer for eligibility purposes
- •Current systemic chemotherapy or radiation therapy that potentially causes bone marrow suppression that would preclude safe treatment of HSIL
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to VGX-3100
- •Warts so extensive that they preclude the clinician from determining the extent and location of HSIL
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements or could be negatively affected by the electroporation treatment
- •Presence of unstable or life-threatening cardiac disease (e.g. unstable angina, class 3 or higher congestive heart failure)
- •Presence of acute or chronic bleeding or clotting disorder that would be a contraindication to IM injections (which may include the use blood thinners such as anticoagulants or antiplatelets drugs within two weeks of enrollment). Exception: Over-the-counter aspirin or non-steroidal anti-inflammatory drugs is allowed.
- •Participants who have not recovered from adverse events due to prior anti-HSIL therapy (i.e., have residual toxicity > grade 1), per Common Toxicity Criteria for Adverse Events (CTCAE) v4.0
- •Participants who have any metal implants, implanted medical devices, tattoos, keloids or hypertrophic scars, or active lesions/rashes within 2 cm of all intended potential sites of treatment/electroporation
- •History of seizures, except if participants have been seizure-free for 5 years or more with the use of one or fewer anti-epileptic agents
- •Sustained, manually confirmed, sitting systolic blood pressure > 150 mm Hg or < 90 mm Hg or a diastolic blood pressure > 95 mm Hg at screening or day 0
- •Resting heart rate < 50 beats per minute (bpm) (unless attributable to athletic conditioning) or > 100 bpm at screening or day 0
- •Participants who have less than two acceptable sites available for IM injection considering the deltoid and anterolateral quadriceps muscles
- •Participants who have cardioverter-defibrillator or pacemaker (to prevent a life-threatening arrhythmia) that is located ipsilateral to the deltoid injection site (unless deemed acceptable by a cardiologist)
- •Participants who are breastfeeding a child; investigational product should not be administered to nursing mothers
- •Any illness or condition that in the opinion of the investigator may affect the safety of the participant or the evaluation of any study endpoint
研究组 & 干预措施
Treatment (VGX-3100, electroporation)
Experimental
Patients receive HPV DNA plasmids therapeutic vaccine VGX-3100 IM and then undergo electroporation over 10 seconds for 4 doses in week 0, 4, 12, and 24 in the absence of disease progression or unacceptable toxicity.
干预措施: HPV DNA Plasmids Therapeutic Vaccine VGX-3100 (Biological)
Treatment (VGX-3100, electroporation)
Experimental
Patients receive HPV DNA plasmids therapeutic vaccine VGX-3100 IM and then undergo electroporation over 10 seconds for 4 doses in week 0, 4, 12, and 24 in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (VGX-3100, electroporation)
Experimental
Patients receive HPV DNA plasmids therapeutic vaccine VGX-3100 IM and then undergo electroporation over 10 seconds for 4 doses in week 0, 4, 12, and 24 in the absence of disease progression or unacceptable toxicity.
干预措施: Electroporation (Device)
结局指标
主要结局
Overall response rate at 48 weeks
时间窗: At 48 weeks
Defined as histopathological regression of human papillomavirus (HPV)-16 and/or 18-positive anal high grade squamous intraepithelial neoplasia (HSIL) to low grade squamous intraepithelial neoplasia (LSIL) \[anal intraepithelial neoplasia (AIN)1\] or normal.
次要结局
- Safety and tolerability of treatment as assessed by incidence of adverse events(Up to 48 weeks)
- Viral clearance histological specimen(At 48 weeks)
- Overall response rate at 72 weeks(At 72 weeks)
- Viral clearance anal swab(Up to 48 weeks)
- Complete response rate(At 48 weeks)
- Viral Clearance Anal Swab(Up to 48 weeks)
研究者
研究点 (16)
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