Randomized double-blind, placebo-controlled study of topical diclofenac in prevention of hand-foot syndrome in patients receiving capecitabine
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 264
- 试验地点
- 1
- 主要终点
- To compare the effect of topical diclofenac with placebo in preventing clinically significant hand foot syndrome [HFS] (incidence of National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 5.0 grade 2 or higher HFS)
研究概览
简要总结
| Background |
The pathophysiology of hand-foot syndrome (HFS) includes activation of cyclooxygenase (COX)-2, leading to an upregulation of the inflammatory cascade. No clinical trials have assessed the role of topical non-steroidal anti-inflammatory drugs (NSAIDs) in preventing HFS.
|General Aim
To determine the efficacy and safety of topical diclofenac in reducing the incidence of HFS in patients receiving capecitabine .
|Primary Objective (Endpoint)
To compare the effect of topical diclofenac with placebo in preventing clinically significant HFS (incidence of NCI CTCAEv5.0 grade 2 or higher HFS)
|Secondary Objectives (Endpoint)
To compare the effect of topical diclofenac with placebo on:
1. Incidence of NCI CTCv5.0 all grade HFS
2. Time to develop grade ≥2 HFS (from start of capecitabine)
3. Patient-reported outcomes (PROs) (HFS-14 questionnaire)
4. Adherence with diclofenac/ moisturiser application (self-reported)
5. Capecitabine dose reductions, delays and cessation due to HFS (number of patients with dose modifications due to HFS)
6. Safety profile (NCICTCv5.0 all grade HFS)
|Tertiary Objective (Endpoint)
7. To correlate the occurrence and severity of HFS with COX-2 levels (Serum COX-2 levels) and polymorphism of DPPD enzyme
|Design
Randomized double-blind, placebo-controlled parallel group study
|Target population
Patients with any stage breast or gastrointestinal cancers, who are starting capecitabine monotherapy. Key exclusion criteria include pre-existing dermatological conditions, peripheral neuropathy and known allergy to NSAIDs.
|Study treatments
Experimental arm: Twice daily application of 1 gm 1% topical diclofenac to the palmar and dorsal surface of both hands for 12 weeks or > grade 2 HFS, whichever is earlier
Control arm: Twice daily application of matched placebo to the palmar and dorsal surface of the both hands for 12 weeks or > grade 2 HFS, whichever is earlier
|Assessments
HFS will be assessed by the treating physicians every 3 weeks in the clinic. All participating physicians will be trained in grading HFS. Photographs will be taken at baseline and every 3 weeks and will be reviewed by an independent blinded investigator to confirm grading of HFS. PROs will be recorded and serum COX-2 levels will be measured at two time points: baseline and 12 weeks or > grade 2 HFS, whichever is earlier
|Statistical considerations
With 120 patients in each study arm, there will be at least 80% power to detect a difference in HFS rates at a two-sided 0.05 significance level, using a chi-square test. This assumes that the rate of grade 2 or higher HFS is 30% in the control arm and 15% in the experimental arm. Assuming approximately 10% attrition, we plan to recruit 264 patients (randomised 1:1 to each treatment).
研究设计
- 研究类型
- Interventional
- 分配方式
- Stratified block randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Age ≥ 18 years 2.Starting capecitabine for breast and GI malignancies, either in adjuvant/neoadjuvant or palliative setting 3.Commencing capecitabine at a dose of ≥1000mg/m2 twice daily every 2 out of 3 weeks as single-agent chemotherapy 4.Life expectancy greater than 12 weeks 5.Eastern Cooperative Oncology Group (ECOG) performance status 0-2 6.Study treatment both planned and able to start within 14 days of randomisation 7.Willing and able to comply with all study requirements, including treatment (applying diclofenac gel), timing and/or nature of required assessments 8.Signed, written informed consent.
排除标准
- •1.Pre-existing grade 2 or higher neuropathy confounding assessment of HFS 2.Other dermatologic condition, that, in the opinion of the physician, may affect the hands or feet or may complicate evaluation during study treatment 3.Concurrent or planned use of pyridoxine 4.Allergy or anaphylactic reactions with NSAIDs 5.History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs 6.Patients receiving oral or topical NSAIDs for other conditions 7.Concurrent illness, including severe infection that may jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety.
- •8.Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.
- •9.Pregnant or lactating women.
结局指标
主要结局
To compare the effect of topical diclofenac with placebo in preventing clinically significant hand foot syndrome [HFS] (incidence of National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 5.0 grade 2 or higher HFS)
时间窗: Baseline and 12 weeks
次要结局
- To compare the effect of topical diclofenac with placebo on:(1.Incidence of NCI CTCv5.0 all grade HFS)
- To correlate the occurrence and severity of HFS with COX-2 levels (Serum COX-2 levels) and polymorphism of DPPD enzyme(Baseline and 12 weeks)