A Phase II Placebo Controlled, Multicenter Study to Investigate the Safety and Efficacy of ATH008 Cream in Patients With Palmar-Plantar Erythrodysesthesia Syndrome (PPES) Secondary to Capecitabine Therapy.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 122
- 试验地点
- 26
- 主要终点
- Efficacy of ATH008 cream in reducing the number of subjects presenting PPES grade 2/3 secondary to capecitabine therapy
研究概览
简要总结
The aim of this study is to evaluate the safety and efficacy of ATH008 cream in patients with Palmar-Plantar Erythrodysesthesia Syndrome (PPES) secondary to capecitabine therapy. In part I, the safety and plasmatic levels of the active ingredient and its metabolite will allow to determine the most appropriate and beneficial dose for the second part of the study. In Part II, the efficacy of ATH008 cream in reducing the number of patients presenting PPES grade 2/3 secondary to capecitabine therapy following a four times daily application will be tested.
详细描述
This is a Phase II Placebo Controlled, Multicenter Study that will involve up to 114 patients with Palmar-Plantar Erythrodysesthesia Syndrome (PPES) secondary to capecitabine therapy. Eligible patients will be enrolled into Part I or Part II of the study.
The first part of the study (Part I) is designed
- to demonstrate the safety of ATH008 cream 1%, 3% and 8% and ATH008 cream placebo,
- to determine the plasmatic levels of the active ingredient and its metabolite after repeated doses of ATH008 cream 1%, 3% and 8%, and
- to determine the grade of PPES at Day 1 and Day 21 of ATH008 cream treatment Part I will have four different arms; patients will receive one of the three different doses of drug product (ATH008 cream 1%, ATH008 cream 3% or ATH008 cream 8%) or placebo (ATH008 cream placebo) in repeated doses (twice daily) during a period of 21 days.
Patients will continue to be assessed for safety and pharmacokinetics of active ingredient and its metabolite (Pre-dose, Day 1 and Day 21). Results of Part I will determine the most appropriate and beneficial dose for the second part of the study.
The second part of the study (Part II) is aimed at demonstrating the safety and efficacy of ATH008 cream in reducing the number of patients presenting PPES grade 2/3 secondary to capecitabine therapy following a four times daily application.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •Are under capecitabine monotherapy for treatment of colon or breast cancer at a regimen of 2 weeks on and 1 week off (14+7) and a daily doses between 2000 and 2500 mg/m
- •Diagnosis of PPES grade 1 in any hand or foot according to the NCI CTCAE v4.03 definition.
- •In Part I, subjects still have to undergo at least 1 planned cycle with capecitabine monotherapy.
- •In Part II, subjects still have to undergo at least 2 planned cycles with capecitabine monotherapy.
排除标准
- •Are younger than 18 years.
- •Use of other chemotherapies for the treatment of cancer except trastuzumab (Herceptin®) or bevacizumab (Avastin®).
- •Diagnosis of PPES grade 1 in any hand or foot according to the NCI CTCAE v4.03 definition for more than 2 cycles previously to inclusion in this clinical study.
- •Have neurologic symptoms greater than grade 1, which under the criteria of the clinician could interfere with PPES diagnosis or study treatment (e.g. hands or feet neuropathy).
- •Have any dermatologic condition that in the opinion of the investigator may affect hands or feet or may complicate evaluation during study treatment (e.g. neurodermatitis, psoriasis, etc).
- •Have onycholysis with a non-stable grade 1 or onycholysis greater than grade 1 (nail loss, NCI CTCAE v4.03 criteria) which in the assessment of the clinician could interfere with PPES diagnosis or study treatment.
- •Need to use other emollient creams or other topical treatments in hands and/or feet during the study.
- •Are receiving radiotherapy.
- •Have received topical corticosteroids in hands or feet 7 days prior to planned inclusion in the study.
- •Are participating in any other investigational studies for the treatment of PPES.
- •Have participated in any other investigational studies for the treatment of PPES, or received an experimental therapeutic procedure, considered to potentially interfere with the study in the 4 weeks preceding Day
- •The above is not a complete list of eligibility criteria. Please see your study doctor for more information.
研究组 & 干预措施
ATH008 cream 3%
ATH008 cream 3%
干预措施: ATH008 (Drug)
ATH008 cream 8%
ATH008 cream 8%
干预措施: ATH008 (Drug)
ATH008 cream placebo
ATH008 cream placebo
干预措施: ATH008 (Drug)
结局指标
主要结局
Efficacy of ATH008 cream in reducing the number of subjects presenting PPES grade 2/3 secondary to capecitabine therapy
时间窗: minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days
percentage of subjects that develop PPES grade 2 or 3 according to the NCI CTCAE v4.03 criteria
Safety of ATH008 cream in patients presenting PPES secondary to capecitabine therapy
时间窗: minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days
adverse events and serious adverse events (incidence, causality, and severity) related to treatment with ATH008 cream
Plasmatic levels of ATH008 cream when given topically
时间窗: blood sampling at specific timepoints (Pre-dose, Day 1 and Day 21)
plasmatic levels of the active ingredient and its metabolite when given topically
次要结局
- Efficacy of ATH008 cream in improving the quality of life of patients presenting PPES(minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days)
- Efficacy of ATH008 cream in improving signs and symptoms of PPES(minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days)
- Assessment of patient reported pain(minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days)
- Accumulated dose intensity of capecitabine before and during ATH008 cream treatment(minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days)