Clinical trial NCT01136005: Bepanthen Versus Cetomacrogol in Epidermal Growth Factor Receptor Inhibitors (EGFRI)
Official title: Phase III Randomized Double-Blind Trial of Bepanthen® Cream Versus Cetomacrogol Cream in the Prevention of Papulopustular Eruption in Patients Receiving Epidermal Growth Factor Receptor Inhibitors (EGFRI): BeCet
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cancer
Skin Rash
Keywords: receptor, epidermal growth factor
skin reactions
quality of life
adherence
Lead sponsor: Impaqtt Foundation
Sponsor class: OTHER
Collaborators: name: CB Boers ORG
name: Memorial Sloan Kettering Cancer Center
name: Leiden University Medical Center
name: Bayer
First posted: 2010-06-03
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Objective:

To assess the preemptive effect of Bepanthen® on decreasing the incidence of specific ≥ grade 2 dermatological side effects of interest in respect of compliance to EGFRI agents, HRQoL and the adherence during the 6-week skin treatment period. The adherence to the study creams will also be studied.

Detailed description: Rationale:

Dermatological side effects, such as papulopustular eruption, xerosis, pruritus, periungual inflammation, mucosal-, and hair abnormalities, and edema occur in up to 90% of patients during treatment with epidermal growth factor receptor inhibitors (EGFRI). Patients are hindered in their daily activities and cannot maintain privacy about their illness because of the prominent side effects. The aesthetic discomfort, which is frequently associated with itching or painful skin or nails can lead to a decreased health related quality of life (HRQoL) and to dose reduction or discontinuation of anticancer treatment.

Patients with dermatological side effects have also an increased risk for cutaneous infections (at least 38%) which can complicate dermatological side effects.

At present, evidence of the effectiveness of the management options for dermatological side effects is lacking, and the effect of the dermatological side effects on HRQoL and adherence remains poorly understood.

Dexpanthenol cream (Bepanthen®, Bayer) has been used extensively to ameliorate acute radiation induced skin toxicity, diaper dermatitis, irritant hand dermatitis, graft-donor site wound healing and burn patients. The hypothesis is that its skin healing possibilities decreases this kind of side effects.

Study design:

Multicenter, two-arm randomized, double blind, prospective parallel group design, phase III study

Study population:

Each patient starting for the first time with EGFRI anticancer therapy which can cause papulopustular eruption (cetuximab, panitumumab, erlotinib, gefitinib, lapatinib, or other), will be included.

Intervention:

80 patients will receive for the first 6 weeks of treatment Bepanthen cream, 80 patients Cetomacrogol cream to apply twice daily. Using FACT-EGFRI, a dermatology-specific questionnaire, this study examines the effect of these side effects on three domains of HRQoL - symptoms, emotions, and functioning. Severity of dermatological side effects will be assessed using the NCI-CTCAE v4.0. Correlation of dermatology HRQoL scores with NCI-CTCAE grade, sex, age, type of EGFRI, and cancer type will be conducted.

Eligibility criteria: Inclusion Criteria:

* Male and female subjects
* ≥18 years of age.
* Patients must have signed an approved informed consent form prior to registration on study.
* Histological proof of cancer.
* A planned course of EGFRI treatment for any type of cancer. Patients must be entered on study ≤ 7 days before EGFRI treatment begins.
* Have an Eastern Co-operative Oncology Group (ECOG) performance status ≤ 2.
* Ability to complete questionnaire(s) by themselves or with assistance.
* Patients need to be free of infection and not using any topical treatments on the skin.

Exclusion Criteria:

* Use of other concurrent topical creams or lotions at baseline.
* Concomitant use of medications that may affect trial results (e.a. concurrent use of topical antibiotics, topical steroids, and other topical treatments on face and chest within 14 days of Day 0 (baseline); treatment with any systemic antibiotics within 7 days prior to Day 0.
* Active dermatological conditions other than papulopustular eruption that may affect trial results. A skin examination reveals the presence of another skin disease in face or chest that may obscure rash to EGFRI and/or condition (excessive facial hair, excessive scarring, sunburn, or other disfigurement) located on the skin that, in the study physician's opinion, would confound the evaluation of the papulopustular eruption.
* Known allergy or hypersensitivity to ingredients in Bepanthen® or Cetomacrogol.
* Known sensitivity, papulopustular eruption or other abnormal skin reaction to topical or systemic medications or cleansing products at baseline.
* Prior treatment with targeted therapy of any kind.
* Current use of agents that are known to be strong inducers or inhibitors of CYP3A4 that can not be stopped

Primary outcomes:
measure: grade 2 or more papulopustular eruption
timeFrame: 6 weeks
measure: impact of papulopustular eruptions on HRQoL
timeFrame: 6 weeks
Secondary outcomes:
measure: patient tolerability and satisfaction of study cream
timeFrame: 6 weeks
measure: effectiveness of study cream on the adherence
timeFrame: 6 weeks
measure: other dermatological side effects
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Alkmaar
country: Netherlands
facility: Medisch Centrum Alkmaar
city: Deventer
country: Netherlands
facility: Deventer ziekenhuis
city: Goes
country: Netherlands
facility: Admiraal de Ruyter Hospital
city: Leiden
country: Netherlands
facility: Leiden University Medical Centre
city: Purmerend
country: Netherlands
facility: Waterland Hospital
city: Zaandam
country: Netherlands
facility: Zaans Medisch Centrum
Study officials:
affiliation: Waterland Hospital, Purmerend, the Netherlands
name: Christine Boers-Doets, MSc
role: STUDY_CHAIR
affiliation: Memorial Sloan-Kettering Cancer Center, USA
name: Mario Lacouture, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Leiden University Medical Centre, the Netherlands
name: Johan Nortier, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Clabbers JMK, Boers-Doets CB, Gelderblom H, Stijnen T, Lacouture ME, van der Hoeven KJM, Kaptein AA. Xerosis and pruritus as major EGFRI-associated adverse events. Support Care Cancer. 2016 Feb;24(2):513-521. doi: 10.1007/s00520-015-2781-y. Epub 2015 Jun 27.
citation: Boers-Doets CB, Gelderblom H, Lacouture ME, Epstein JB, Nortier JW, Kaptein AA. Experiences with the FACT-EGFRI-18 instrument in EGFRI-associated mucocutaneous adverse events. Support Care Cancer. 2013 Jul;21(7):1919-26. doi: 10.1007/s00520-013-1752-4. Epub 2013 Feb 17.