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

Primary Purpose

Hand-foot Syndrome

Status
Terminated
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Brimonidine Tartrate
Sponsored by
Heinrich-Heine University, Duesseldorf
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hand-foot Syndrome focused on measuring Hand-foot Syndrome, Brimonidine, Mirvaso, palmar-plantar erythrodysesthesia syndrome, Brimonidine Tartrate

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Universitätsklinikum Düsseldorf, Klinik für Dermatologie

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Brimonidine Tartrate

Arm Description

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.

Outcomes

Primary Outcome Measures

Number and time of occurence of Palms with HFS severity grade 2 or 3
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

Secondary Outcome Measures

NCI-CTCAE v4.0 grading of HFS severity
Severity of HFS after 2 cycles of chemotherapy or 6 weeks by means of the NCI-CTCAE v4.0 grading
Severity of nail toxicity
Severity of nail toxicity after 2 cycles of chemotherapy or 6 weeks by means of the NCI-CTCAE v3.0 grading
modified ppPASI grading of HFS severity
Severity of HFS after 2 cycles of chemotherapy or 6 weeks by means of a modified Palmoplantar Psoriasis Area Severity Index (ppPASI)
computer-assisted quantification of HFS severity
Severity of HFS after 2 cycles of chemotherapy or 6 weeks by means of computer-assisted quantification
HFS associated pain (by VAS scale)
Level of HFS-associated pain after 2 cycles of chemotherapy or 6 weeks by means of visual analogue scale (VAS)
Highest grade of HFS severity (NCI-CTCAE v4.0 grading)
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

Full Information

First Posted
May 30, 2017
Last Updated
January 7, 2019
Sponsor
Heinrich-Heine University, Duesseldorf
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1. Study Identification

Unique Protocol Identification Number
NCT03173365
Brief Title
The Effect of Topical Brimonidine Tartrate on Hand-foot Syndrome (HFS) in Cancer Patients
Acronym
BRIMOCAN
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Terminated
Why Stopped
It is no longer practicable to complete the trial
Study Start Date
July 10, 2017 (Actual)
Primary Completion Date
December 31, 2018 (Actual)
Study Completion Date
December 31, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Heinrich-Heine University, Duesseldorf

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hand-foot Syndrome
Keywords
Hand-foot Syndrome, Brimonidine, Mirvaso, palmar-plantar erythrodysesthesia syndrome, Brimonidine Tartrate

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
The respective palm to be treated will be randomly assessed and will be matched for handedness to include equal numbers of dominant and non-dominant treated palms.
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Brimonidine Tartrate
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Brimonidine Tartrate
Other Intervention Name(s)
Mirvaso
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number and time of occurence of Palms with HFS severity grade 2 or 3
Description
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
Time Frame
weekly up to 6 weeks
Secondary Outcome Measure Information:
Title
NCI-CTCAE v4.0 grading of HFS severity
Description
Severity of HFS after 2 cycles of chemotherapy or 6 weeks by means of the NCI-CTCAE v4.0 grading
Time Frame
weekly up to 6 weeks
Title
Severity of nail toxicity
Description
Severity of nail toxicity after 2 cycles of chemotherapy or 6 weeks by means of the NCI-CTCAE v3.0 grading
Time Frame
weekly up to 6 weeks
Title
modified ppPASI grading of HFS severity
Description
Severity of HFS after 2 cycles of chemotherapy or 6 weeks by means of a modified Palmoplantar Psoriasis Area Severity Index (ppPASI)
Time Frame
weekly up to 6 weeks
Title
computer-assisted quantification of HFS severity
Description
Severity of HFS after 2 cycles of chemotherapy or 6 weeks by means of computer-assisted quantification
Time Frame
weekly up to 6 weeks
Title
HFS associated pain (by VAS scale)
Description
Level of HFS-associated pain after 2 cycles of chemotherapy or 6 weeks by means of visual analogue scale (VAS)
Time Frame
weekly up to 6 weeks
Title
Highest grade of HFS severity (NCI-CTCAE v4.0 grading)
Description
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
Time Frame
weekly up to 6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Arne Gerber, PD Dr. med.
Organizational Affiliation
Heinrich-Heine University, Duesseldorf
Official's Role
Principal Investigator
Facility Information:
Facility Name
Universitätsklinikum Düsseldorf, Klinik für Dermatologie
City
Düsseldorf
ZIP/Postal Code
40225
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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