Effect of Topical Diclofenac on Clinical Outcome in Breast Cancer Patients Treated With Capecitabine

January 1, 2024 updated by: German University in Cairo

Effect of Topical Diclofenac on Clinical Outcome in Breast Cancer Patients Treated With Capecitabine: A Randomized Controlled Trial.

The aim of the study is to evaluate the efficacy of using combination of Urea-based cream (CARBAMIDE®) and topical diclofenac (VOLTAREN®) Emulgel 1% for improving the incidence of Hand-foot syndrome in histologically proven breast cancer Egyptian patients receiving single agent chemotherapy Capecitabine (XELODA ®) and Its effect on improving patients' quality of life.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Breast cancer (BC) is the most common cancer in women and the leading cause of death associated with cancer in females worldwide. BC, like most cancers, is a heterogeneous disease with a variety of molecular subtypes. Basal-like, Luminal-A, Luminal-B, HER2-positive/HER2-enriched/HER2-overexpressing BC, and normal-like tumors are the major subclasses identified by genetic profiling. Depending on the size, stage, grade, metastatic behavior, aggressiveness and intrinsic molecular subtyping of the tumor, age, menopausal status, overall health, comorbidities, and preferences of the patient, clinicians now have numerous options for breast cancer treatment. Treatment options include chemotherapy, hormone therapy, immunotherapy, radiotherapy, and surgery. The primary treatment option is usually surgery with the goal of complete resection of the major tumor mass. Surgery may be preceded by systemic neoadjuvant therapies to shrink the tumor in preparation for effective surgery and to maximize breast conservation.

The United States FDA has approved a number of drugs for breast cancer therapy, including Capecitabine (Xeloda). However, these drugs are very pricey and have numerous side effects. Patients frequently report decreased appetite, dehydration, diarrhea, Hand-foot syndrome (HFS), irregular periods, mouth and throat sores, nausea, and vomiting as side effects of Capecitabine. These side effects are difficult for patients who are already weakened by the disease to tolerate. Eventually these also affect the decision for further choice of treatment and impair the quality of life. This necessitates the development of novel drugs for the treatment of breast cancer and This is the role of drug repurposing.

The drug repositioning (aka drug repurposing, drug reprofiling, drug re-tasking, drug redesigning, drug resorting, drug reindication, indication switching, therapeutic switching) can be defined as exploring the new uses for an old clinically approved drug, with reduced risk, time and cost. Methotrexate, Raloxifene and Vinblastine are examples of Drug repurposing in breast cancer.

Hand-foot syndrome (HFS) also Known as palmoplantar erythrodysesthesia, is a common side effect of the fluoropyrimidine chemotherapy drug capecitabine. According to reports, 43 % to 71 %of patients receiving single-agent capecitabine chemotherapy have hand-foot syndrome of any grade.

It is characterized initially by palmoplantar numbness, tingling, or burning pain. These symptoms are usually accompanied by clearly defined erythema with or without edema, cracking, or desquamation. Blistering and ulceration may occur in the advanced stages. HFS may manifest as macular hyperpigmentation rather than erythema in people with darker skin (Fitzpatrick skin types V-VI). Symptoms can range from mildly to severely painful.

The pathogenesis of HFS is unclear, but it is assumed to be different for each drug class HFS causes a variety of toxic skin damage, ranging from non-specific scattered keratinocyte necrosis with basal vacuolar degeneration to full epidermal layer necrosis and (sub)epidermal blistering. In addition to eccrine squamous syringometaplasia, inflammation at the dermo-epidermal junction with papillary dermal edema, blood vessel dilation, and a lymphocytic infiltrate has been reported. The unique physiology of the palms and soles may clarify why the effects of these drugs are concentrated in these areas. The palms and soles are highly vascular, with higher rates of skin cell division than other skin areas, as well as high concentrations of eccrine glands and unique temperature modulation.

Unfortunately, no specific guidelines exist for HFS, and only a few randomized trials demonstrating the benefit of topical treatments are available. The most effective way to manage HFS once it has developed is to modify dose intensity in the form of a dose delay or dose reduction, which will affect patients' treatment outcomes and quality of life such as daily activities like walking or using of hands.

The treatment of choice for symptomatic HFS is determined by the severity of symptoms and their impact on Quality of Life (QoL). Vitamin E, steroids (oral dexamethasone), and analgesics are among the systemic treatment options. Current topical treatments are corticosteroids and emollients such as urea-based creams.

Capecitabine and its metabolites are thought to cause COX-2-mediated inflammation; COX-2 inhibition has been shown to be effective in the prevention of HFS. Topical non-steroidal anti-inflammatory inhibitors (NSAIDs), such as diclofenac, can inhibit COX-2 locally and may have a role in reducing HFS, without systemic side effects. However, no study has been conducted to date evaluating the role of topical COX inhibitors in reducing capecitabine-induced HFS. Hence, this study aimed to evaluate the efficacy and safety of topical diclofenac in reducing capecitabine-induced HFS.

Study Type

Interventional

Enrollment (Actual)

86

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Egypt
      • Cairo, Egypt
        • KASR ALAINY Center of Oncology and Nuclear medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Adults aged 18 years and above.
  2. Females.
  3. Histologically proven breast cancer patients receiving Capecitabine (XELODA ®) chemotherapy.
  4. life expectancy greater than 18 weeks.

Exclusion Criteria:

  1. Hypersensitivity to diclofenac, aspirin or other non-steroidal anti-inflammatory drugs (NSAIDS).
  2. History of Urticaria.
  3. History of acute rhinitis
  4. Asthmatic Patients.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Control Arm
  • Standard of care Urea-based cream (CARBAMIDE®) will be applied to hands and feet 2-3 times daily for 14 days starting from the first dose and cycle of Capecitabine (XELODA ®).
  • Each Capecitabine (XELODA ®) cycle lasts for 21 days.
  • Capecitabine (XELODA ®) dose :2g/m2 daily divided into 2 doses after breakfast and dinner for 14 days followed by 7 days Capecitabine free.
  • Capecitabine (XELODA ®) dose will be modified according to treatment related side effects (26).
  • This regimen will be repeated at each cycle of Capecitabine (XELODA ®) and lasts for 6 cycles (18 weeks) and preventive measures of Hand-foot syndrome will be applied (Avoid mechanical stress
Drug: (CARBAMIDE®)
Urea is used to treat dry/rough skin conditions (such as eczema, psoriasis, corns, callus) and some nail problems (such as ingrown nails). It may also be used to help remove dead tissue in some wounds to help wound healing. Urea is known as a keratolytic. It increases moisture in the skin by softening/dissolving the horny substance (keratin) holding the top layer of skin cells together. This effect helps the dead skin cells fall off and helps the skin keep more water in.
Other Names:
  • Urea-based cream
Active Comparator: Intervention Arm
  • Standard of care Urea-based cream (CARBAMIDE®) will be applied to hands and feet twice daily for 14 days starting from the first dose and cycle of Capecitabine (XELODA ®).
  • Each Capecitabine (XELODA ®) cycle lasts for 21 days.
  • Capecitabine (XELODA ®) dose: 2g/m2 daily divided into 2 doses after breakfast and dinner for 14 days followed by 7 days Capecitabine free.
  • Capecitabine (XELODA ®) dose will be modified according to treatment related side effects (26).
  • This regimen will be repeated at each cycle of Capecitabine (XELODA ®) and lasts for 6 cycles (18 weeks) and preventive measures of Hand-foot syndrome will be applied (Avoid mechanical stress Plus
  • Topical diclofenac (VOLTAREN®) Emulgel 1% 2-4g (2g = 4 fingertip Units (FTU)) twice daily 2 hours away from Urea-based cream (CARBAMIDE®) for 14 days starting from the first cycle and dose of Capecitabine.
  • This regimen will be repeated at each cycle of Capecitabine (XELODA ®) and lasts for 6 cycles (18 weeks).
Drug: (VOLTAREN®) Emulgel 1%
(VOLTAREN®) Emulgel 1% contain the active ingredient diclofenac which belongs to the NSAIDS.it has analgesic and anti-inflammatory properties and due to its alcohol base it has a cooling effect.
Other Names:
  • Diclofenac Sodium
Drug: (CARBAMIDE®)
Urea is used to treat dry/rough skin conditions (such as eczema, psoriasis, corns, callus) and some nail problems (such as ingrown nails). It may also be used to help remove dead tissue in some wounds to help wound healing. Urea is known as a keratolytic. It increases moisture in the skin by softening/dissolving the horny substance (keratin) holding the top layer of skin cells together. This effect helps the dead skin cells fall off and helps the skin keep more water in.
Other Names:
  • Urea-based cream

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
• Incidence of HFS between control arm (Urea-based cream (CARBAMIDE®)) and intervention arm (Combination of Urea-based cream (CARBAMIDE®) and (VOLTAREN®) Emulgel 1%) measured by (CTCAE v 5.0).
Time Frame: One year
• Incidence of HFS between control arm (Urea-based cream (CARBAMIDE®)) and intervention arm (Combination of Urea-based cream (CARBAMIDE®) and (VOLTAREN®) Emulgel 1%) measured by (Common Terminology Criteria for Adverse Effects CTCAE v 5.0).
One year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

German University in Cairo

Collaborators

Cairo University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 8, 2022

Primary Completion (Actual)

November 15, 2023

Study Completion (Actual)

December 8, 2023

Study Registration Dates

First Submitted

November 9, 2022

First Submitted That Met QC Criteria

November 29, 2022

First Posted (Actual)

December 7, 2022

Study Record Updates

Last Update Posted (Estimated)

January 3, 2024

Last Update Submitted That Met QC Criteria

January 1, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CPH-2022-10-MHS-2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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