Treatment of Palmar Plantar Erythrodysesthesia (PPE) With Topical Sildenafil
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Grade of hand foot syndrome over time as measured by NCI CTC version 4.0 PPE syndrome criteria
研究概览
简要总结
Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysethesia (PPE), occurs in a 25%-50% of patients treated with several commonly used anti-cancer drugs including capecitabine and sunitinib. These drugs are known to improve survival in many cancers, including cancers of the colon, stomach, liver, breast, kidney, and GI stromal tumors (GIST). Worldwide, over 400,000 patients per year are treated with one of these agents. HFS involves skin changes, such as swelling, peeling, and blistering of the palms and soles, which is often painful and debilitating. As a result, HFS-related symptoms can frequently lead to dose reduction and/or discontinuation of otherwise effective anti-cancer treatment. There is no treatment for HFS other than dose reduction or stopping treatment. This proposal could quickly lead to treatments to prevent and/or treat HFS and help patients avoid debilitating side effects while continuing otherwise effective treatments for their cancer.
详细描述
The primary objective is to evaluate whether topical sildenafil reduces the severity of hand foot syndrome or palmar plantar erythrodysesthesia (PPE) associated with sunitinib and capecitabine. The secondary objective is to describe any toxicities associated with topical sildenafil.
This is a randomized, double blind, placebo-controlled pilot study of topical sildenafil for patients with grade 1-3 hand foot syndrome related to chemotherapeutic agents.
Approximately 20 evaluable patients with grade 1-3 PPE will be treated with topical sildenafil:
- 10 patients with PPE related to sunitinib
- 10 patients with PPE related to capecitabine
Once eligibility and screening criteria are met, subjects will be given 2 types of topical cream, one containing 1% sildenafil citrate and one containing placebo control. Subjects will be randomized to apply sildenafil citrate cream to either the right or left hand/foot; placebo cream will be applied to the opposite hand/ foot.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must meet the following criteria to be eligible for the study:
- •Receiving capecitabine or sunitinib as part of routine standard care.
- •CTCAE version 4.0, grade 1-3 PPE.
- •Adults age ≥ 18
- •Karnofsky (KPS) performance status of ≥70%
- •Adequate organ and marrow function as defined below:
- •ANC > 1000/mL
- •Platelets > 75,000/mL
- •Total bilirubin < 1.5 x UNL
- •AST(SGOT)/ALT(SGPT) < 5 x UNL
- •Creatinine Cr Cl est > 40 mL/min (by Cockcroft-Gault)
- •Not pregnant or lactating.
- •Use of adequate birth control with female partners of male subjects agreeing to use a medically acceptable form of birth control: (1) surgical sterilization, (2) approved hormonal contraceptives (such as birth control pills or Depo-Provera), (3) barrier methods (such as a condom or diaphragm) used with a spermicide, (4) an intrauterine device (IUD) or (5) post menopausal. Abstinence is not considered acceptable birth control. Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Subjects meeting any of the following criteria are ineligible for study entry:
- •Currently participating in a clinical trial.
- •History of hypersensitivity or intolerance to sildenafil or other related products tadalafil (Cialis™), vardenafil (Levitra™) or poloxamer vehicle.
- •Currently taking oral sildenafil or other related products tadalafil (Cialis™), vardenafil (Levitra™).
- •Currently taking other treatment for PPE other than standard emollients.
- •Using organic nitrates, either regularly and/or intermittently, in any form.
- •History of myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months.
- •Resting hypotension (BP <90/50 mmHg) or hypertension (BP >170/110 mmHg). Those subjects on alpha-blocker or anti-hypertensive therapy must be hemodynamically stable for at least two weeks before day 1 of study drug.
- •Cardiac failure or coronary artery disease causing unstable angina.
- •Known retinitis pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases).
- •Concomitant use of strong cytochrome P450 3A4 inducers or inhibitors (Ex: ketoconazole, itraconazole, erythromycin, saquinavir).
- •Other acute or chronic inflammatory conditions or infections of the hands or feet that would complicate safety, application of topical creams, or study endpoints.
- •History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.
- •Pregnant or breast-feeding and/or lactating.
- •Inability or unwillingness to comply with protocol.
结局指标
主要结局
Grade of hand foot syndrome over time as measured by NCI CTC version 4.0 PPE syndrome criteria
时间窗: Every 2 weeks (sunitinib arm); Every 3 weeks (capecitabine arm)
Grading of PPE by NCI CTC criteria occurs every 2 weeks for subjects in the sunitinib arm for 1st 8 weeks (and as clinically indicated). Grading of PPE by NCI CTC criteria occurs every 3 weeks for subjects in the capeccitabine arm for the 1st 9 weeks (and as clinically indicated)
Assessment of patient reported pain, at rest and when making a fist, using a 1-10 score.
时间窗: twice daily
Assessment of patient reported pain, at rest and when making a fist, using a 1-10 score, is collected on a diary card that subjects fill out twice daily.
Assessment of severity of erythema and desquamation or blistering as measured on 0-4 score from photographs.
时间窗: Every 2 weeks (sunitinib arm); Every 3 weeks (capecitabine arm)
Assessment of severity of erythema and desquamation or blistering as measured on 0-4 score from photographs of hands and/or feet taken every two weeks (for subjects in sunitinib arm) or every 3 weeks (for subjects in capecitabine arm).
次要结局
未报告次要终点