Clinical trial NCT03173365: The Effect of Topical Brimonidine Tartrate on Hand-foot Syndrome (HFS) in Cancer Patients
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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hand-foot Syndrome
Keywords: Hand-foot Syndrome
Brimonidine
Mirvaso
palmar-plantar erythrodysesthesia syndrome
Brimonidine Tartrate
Lead sponsor: Heinrich-Heine University, Duesseldorf
Sponsor class: OTHER
First posted: 2017-06-01
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number and time of occurence of Palms with HFS severity grade 2 or 3
timeFrame: weekly up to 6 weeks
Secondary outcomes:
measure: NCI-CTCAE v4.0 grading of HFS severity
timeFrame: weekly up to 6 weeks
measure: Severity of nail toxicity
timeFrame: weekly up to 6 weeks
measure: modified ppPASI grading of HFS severity
timeFrame: weekly up to 6 weeks
measure: computer-assisted quantification of HFS severity
timeFrame: weekly up to 6 weeks
measure: HFS associated pain (by VAS scale)
timeFrame: weekly up to 6 weeks
measure: Highest grade of HFS severity (NCI-CTCAE v4.0 grading)
timeFrame: weekly up to 6 weeks
Other outcomes:
Locations:
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf, Klinik für Dermatologie
Study officials:
affiliation: Heinrich-Heine University, Duesseldorf
name: Peter Arne Gerber, PD Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: