A study of topical diclofenac gel to prevent hand foot syndrome due to capecitabine in breast and gastrointestinal cancers

Phase 3

Active, not recruiting

Conditions: Malignant neoplasm of breast, (2) ICD-10 Condition: C15-C26||Malignant neoplasms of digestive organs,

Registration Number: CTRI/2021/01/030592

Lead Sponsor: Indian Association of Supportive Care in Cancer

Brief Summary: | | |

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|**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 â‰¥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).

Detailed Description: Not available

Recruitment & Eligibility

Status: Closed to Recruitment of Participants

Sex: All

Target Recruitment: 264

Inclusion Criteria

1.Age â‰¥ 18 years 2.Starting capecitabine for breast and GI malignancies, either in adjuvant/neoadjuvant or palliative setting 3.Commencing capecitabine at a dose of â‰¥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.

Exclusion Criteria

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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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)	Baseline and 12 weeks

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1): All India Institute of Medical Sciences
🇮🇳
South, DELHI, India
All India Institute of Medical Sciences
🇮🇳South, DELHI, India
Dr Atul Batra
Principal investigator
01129575232
batraatul85@gmail.com