Phase IIB Study to Evaluate the Safety and Efficacy of Topical Difluoromethylornithine and Topical Diclofenac in the Treatment of Sun-Damaged Skin on the Forearm
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 184
- 试验地点
- 3
- 主要终点
- Safety of Combination Therapy With Topical Eflornithine Hydrochloride Ointment and Topical Diclofenac Sodium Gel Over 3-months
研究概览
简要总结
RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of eflornithine and diclofenac may stop cancer from growing in patients with sun-damaged skin.
PURPOSE: This randomized phase II trial is studying the side effects and how well eflornithine works compared with diclofenac, given alone or together, in treating patients with sun-damaged skin.
详细描述
OBJECTIVES:
Primary
- To determine if combination therapy with topical eflornithine hydrochloride ointment and topical diclofenac sodium gel over 3-months increases the efficacy versus either agent used alone in the treatment of moderately sun-damaged skin.
Secondary
- To evaluate the safety of sequential administration of topical eflornithine hydrochloride ointment and topical diclofenac sodium gel.
- To determine the correlation of karyometric changes with histopathologic, immunohistochemical, clinical, and genetic polymorphism data.
- To obtain materials for microarray analysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Visible sun-induced damage to the skin as assessed by the study dermatologists
- •No inflammation of the skin on the lateral forearms
- •No more than 10 actinic keratoses on the left forearm, and no actinic keratoses in the treatment area
- •Resident of Pima or an adjoining Southern Arizona county
- •History of treated basal cell carcinoma and/or squamous cell carcinoma of the skin at any site other than the left forearm allowed if excision or topical treatment was completed more than 30 days ago (60 days for radiotherapy)
- •History of treated basal cell carcinoma and/or squamous cell carcinoma of the skin on the left forearm allowed 6 months after treatment is completed
- •Must agree to avoid sun exposure to the left forearm as much as possible
- •Not pregnant or nursing
- •Not moderately to highly immunosuppressed by virtue of medication or disease, except for mildly suppressive disorders (e.g., diabetes mellitus or on mildly immunosuppressive therapy such as inhaled steroids for asthma)
- •No serious concurrent illness that could interfere with study participation
- •No active peptic ulcer disease, bleeding disorder, renal failure (creatinine > 2.0 mg/dL), or porphyria
- •No known hypersensitivity to diclofenac sodium, eflornithine, acetylsalicylic acid, or NSAIDS
- •No evidence of serious underlying medical conditions as demonstrated by abnormal values on baseline laboratory assessment
- •More than 6 months since prior chemotherapy and in complete remission
- •More than 60 days since prior and no concurrent oral diclofenac sodium (Cataflam®, Voltaren®, Voltaren-XR®) or combination of diclofenac and misoprostol (Arthrotec®)
- •More than 60 days since prior and no concurrent IV eflornithine hydrochloride
- •More than 30 days since prior and no concurrent topical retinoids, steroids, imiquimod (Aldara®), aminolevulinic acid HCl (Levulan®), eflornithine (Vaniqa®), diclofenac sodium gel (Solaraze®), or fluorouracil at any site
- •More than 30 days since prior and no concurrent topical medication, other than emollients or sunscreens, on the left forearm
- •Not undergoing concurrent bone marrow or solid organ transplant
- •No concurrent immunosuppressive therapy (e.g., systemic chemotherapy or rheumatologic agents such as infliximab [Remicade®])
- •No concurrent sunscreen use to the left forearm
- •No concurrent active therapy for any invasive cancer
- •No concurrent NSAIDs for more than 14 days per month for arthritic and other pain conditions
- •Concurrent prednisone or other steroids with doses up to 20 mg/day (or the equivalent dose) allowed
- •At least 30 days since prior and no concurrent enrollment on other investigational drug or device trial
排除标准
- •Individuals receiving concurrent topical therapy with retinoids, steroids, 5-fluorouracil, Levulan, Vaniqa (eflornithine), Solaraze, or Imiquimod (Aldara®) within 30 days prior to study enrollment will be excluded. Subjects may be reconsidered for eligibility 30 days after the last topical treatment.
- •Individuals who have had treatment for basal cell carcinoma or squamous cell carcinoma of the skin of the left forearm within six months prior to evaluation for the study will not be eligible. If interested, these subjects will be encouraged to return for re-evaluation once the six-month period is over.
- •Individuals who are moderately to highly immunosuppressed by virtue of medication or disease will not be allowed to participate. This category includes individuals undergoing bone marrow or solid organ transplant, or receiving immunosuppressive therapy such as systemic chemotherapy or rheumatologic agents such as infliximab (Remicade®). However, individuals with mildly suppressive disorders such as diabetes mellitus or on mildly immunosuppressive therapy such as inhaled steroids for asthma will be eligible for participation. Doses up to 20 mg of prednisone per day or the equivalent dose of other steroids will be allowed.
研究组 & 干预措施
Eflornithine HCL
Patients apply Eflornithine HCL ointment to their left forearm twice daily on days 1-90.
干预措施: Eflornithine HCL ointment (Drug)
Diclofenac Na
Patients apply topical Diclofenac Na gel to their left forearm once daily on days 1-90.
干预措施: Diclofenac Na gel (Drug)
Eflornithine HCL and Diclofenac Na
Eflornithine HCl ointment and Diclofenac Na gel applied twice and once daily, respectively on days 1-90.
干预措施: Diclofenac Na gel (Drug)
Eflornithine HCL and Diclofenac Na
Eflornithine HCl ointment and Diclofenac Na gel applied twice and once daily, respectively on days 1-90.
干预措施: Eflornithine HCL ointment (Drug)
结局指标
主要结局
Safety of Combination Therapy With Topical Eflornithine Hydrochloride Ointment and Topical Diclofenac Sodium Gel Over 3-months
时间窗: 3 months
Adverse events were compared across three treatment groups by severity determined by the clinician. All adverse events were resolved by the end of follow up.
Changes in Putrescine Over 3 Months
时间窗: 3 months
Putrescine is measured in nmole/g skin per biopsy. Baseline and End of Study biopsies were measured and the change was produced by subtracting baseline levels from End of Study levels. There was one baseline biopsy and one End of Study biopsy per participant.
次要结局
- Change in Histologic Score Diagnosis and Treatment Group(3 months)