The Effect of Topical Brimonidine Tartrate on Hand-foot Syndrome (HFS) in Cancer Patients (BRIMOCAN)

January 7, 2019 updated by: Heinrich-Heine University, Duesseldorf

Half-Side Controlled Analysis of the Effect of Topical Brimonidine Tartrate on the Frequency and Severity of Hand-Foot Syndrome (HFS) in Cancer Patients Receiving Antineoplastic Agents (BRIMOCAN)

Comparative analysis of the severity of Hand-Foot-Syndrome (HFS) of palms treated with brimonidine tartrate gel or with standard care Urea 10% containing lotion in cancer patients receiving antineoplastic therapy to show a preventive effect of cutaneous brimonidine treatment on severity of HFS symptoms.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Hand-foot syndrome (HFS) is an adverse event frequently associated with the use of classical chemotherapeutic agents such as capecitabine or pegylated liposomal doxorubicin, as well as targeted cancer drugs such as sorafenib or other tyrosine-kinase inhibitors. If the toxicity progresses edematous swelling, blistering and desquamation can lead to ulcerations of the palms and soles. Additionally, patients may be affected by nail-toxicities, such as discoloration, ridging, pitting up to complete onycholysis and pain. Today, cooling of hands and feet during infusion chemotherapy as well as preventive treatment with topical formulations containing urea 10% (e.g. Excipial U10 Lipolotion®) is considered as standard of care. Yet, these strategies are limited by intricateness, patient inconvenience and low efficacy. Hence, at this point the satisfactory treatment of HFS remains an unmet medical need, as until now, no effective therapy is available to prevent or reduce HFS symptoms during the cycle of chemotherapeutic treatment.

Recently, brimonidine 3 mg/g gel (Mirvaso®) has been approved as a topical treatment of facial erythema of rosacea in adult patients. Brimonidine is an effective agonist of α2-adrenoreceptors thereby, in analogy to skin cooling, leading to peripheral vasoconstriction.

Against this background, the following hypothesis was developed:

The topical application brimonidine 3 mg/g gel (Mirvaso®) may prevent or reduce the severity of HFS in cancer patients that receive respective antineoplastic agents.

Study Type

Interventional

Enrollment (Actual)

2

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 Locations

      • Düsseldorf, Germany, 40225
        • Universitätsklinikum Düsseldorf, Klinik für Dermatologie

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

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Cancer patients with solid tumors under antineoplastic therapy with capecitabine or pegylated liposomal doxorubicin.
  • Patients with a life expectancy of at least 12 weeks.
  • History of HFS (grades 2 to 3) in the course of the therapy
  • Patients who are 18-65 years old.
  • Regression of HFS to grade 1 or lower with a symmetrical grading on both hands (grade 0 or grade 1) prior to the next cycle of chemotherapy.
  • not legally incapacitated
  • Written informed consent from the trial subject has been obtained.
  • Current treatment with capecitabine or pegylated liposomal doxorubicin

Exclusion Criteria:

  • Persons with any kind of dependency on the investigator or employed by the sponsor or investigator.
  • Persons held in an institution by legal or official order.
  • Participation in other interventional trials
  • Drug & substance abuse
  • Use of central nervous depressants (e.g. alcohol, barbiturates, opiates, sedatives or anaesthetics)
  • Patients taking alpha adrenergic agonists as medication.
  • Pregnant women and nursing mothers
  • Failure to use highly-effective contraceptive methods

The following contraceptive methods with a Pearl Index lower than 1% are regarded as highly effective:

  • Oral hormonal contraception ('pill')
  • Vaginal hormonal contraception (NuvaRing®)
  • Contraceptive plaster
  • Long-acting injectable contraceptives
  • Implants that release progesterone (Implanon®)
  • Tubal ligation (female sterilization)
  • Intrauterine devices that release hormones (hormone spiral)
  • Double barrier methods: This means that the following are not regarded as safe: condom plus spermicide, simple barrier methods (vaginal pessaries, condom, female condoms), copper spirals, the rhythm method, basal temperature method, and the withdrawal method (coitus interruptus).

    • History of inflammatory dermatosis of hands or feet (e.g. hand eczema)
    • Smoking
    • Severe or unstable or uncontrolled cardiovascular disease
    • Depression
    • cerebral or coronary insufficiency
    • Raynaud's phenomenon
    • orthostatic hypotension
    • thrombangiitis obliterans
    • Scleroderma
    • Sjögren's syndrome
    • renal or hepatic impairment
    • Known allergic sensitization against any of the substances applied in the study
    • Patients receiving monoamine oxidase (MAO) inhibitor therapy (for example selegiline or moclobemide) and patients on tricyclic (such as imipramine) or tetracyclic (such as maprotiline, mianserin or mirtazapin) antidepressants which affect noradrenergic transmission.
    • Patients receiving topical corticoids on hands or feet within 1 week prior to baseline measurement and during the entire study treatment period of up to six weeks.

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: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Brimonidine Tartrate
The respective palm to be treated with Brimonidine will be randomly assessed and will be matched for handedness to include equal numbers of dominant and non-dominant treated palms.
1 gram of Brimonidine 3 mg/g gel (Mirvaso®) in 24 hours on the randomized palm equal to a finger tip unit (FTU) of 0.5 gram , topical application under occlusion twice per day, every 12 hours.
Other Names:
  • Mirvaso

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number and time of occurence of Palms with HFS severity grade 2 or 3
Time Frame: weekly up to 6 weeks
Palms with HFS severity of grade 2 or 3 during 2 cycles of chemotherapy or over 6 week period by means of the National Cancer Institute Common Terminology criteria for Adverse Events (NCI-CTCAE) v4.0 grading
weekly up to 6 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
NCI-CTCAE v4.0 grading of HFS severity
Time Frame: weekly up to 6 weeks
Severity of HFS after 2 cycles of chemotherapy or 6 weeks by means of the NCI-CTCAE v4.0 grading
weekly up to 6 weeks
Severity of nail toxicity
Time Frame: weekly up to 6 weeks
Severity of nail toxicity after 2 cycles of chemotherapy or 6 weeks by means of the NCI-CTCAE v3.0 grading
weekly up to 6 weeks
modified ppPASI grading of HFS severity
Time Frame: weekly up to 6 weeks
Severity of HFS after 2 cycles of chemotherapy or 6 weeks by means of a modified Palmoplantar Psoriasis Area Severity Index (ppPASI)
weekly up to 6 weeks
computer-assisted quantification of HFS severity
Time Frame: weekly up to 6 weeks
Severity of HFS after 2 cycles of chemotherapy or 6 weeks by means of computer-assisted quantification
weekly up to 6 weeks
HFS associated pain (by VAS scale)
Time Frame: weekly up to 6 weeks
Level of HFS-associated pain after 2 cycles of chemotherapy or 6 weeks by means of visual analogue scale (VAS)
weekly up to 6 weeks
Highest grade of HFS severity (NCI-CTCAE v4.0 grading)
Time Frame: weekly up to 6 weeks
Highest grade of HFS severity reached until 2 cycle of chemotherapy or over 6 week period by means of the NCI-CTCAE v4.0 grading
weekly up to 6 weeks

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Peter Arne Gerber, PD Dr. med., Heinrich-Heine University, Duesseldorf

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)

July 10, 2017

Primary Completion (Actual)

December 31, 2018

Study Completion (Actual)

December 31, 2018

Study Registration Dates

First Submitted

May 30, 2017

First Submitted That Met QC Criteria

May 31, 2017

First Posted (Actual)

June 1, 2017

Study Record Updates

Last Update Posted (Actual)

January 9, 2019

Last Update Submitted That Met QC Criteria

January 7, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

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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