Bepanthen Versus Cetomacrogol in Epidermal Growth Factor Receptor Inhibitors (EGFRI) (BeCet)

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

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.

Study Overview

• Status: Completed
• Conditions: Cancer; Skin Rash
• Intervention / Treatment: Other: dexpanthenol 5% cream; Other: Cetomacrogol cream

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.

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Alkmaar, Netherlands, 1815 JD
    • Medisch Centrum Alkmaar
  • Deventer, Netherlands, 7400 GC
    • Deventer Ziekenhuis
  • Goes, Netherlands, 4460 BB
    • Admiraal de Ruyter Hospital
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Centre
  • Purmerend, Netherlands, 1440AG
    • Waterland Hospital
  • Zaandam, Netherlands, 1500 EE
    • Zaans Medisch Centrum

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dexpanthenol 5% cream	Other: dexpanthenol 5% cream; Apply at least two times a day on face, chest and upper arms during the 6 week treatment period; Other Names: Bepanthen; Provitamin
Active Comparator: cetomacrogol cream; a vehicle	Other: Cetomacrogol cream; Apply at least two times a day on face, chest and upper arms during the 6 week treatment period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
grade 2 or more papulopustular eruption	The incidence of grade ≥ 2 papulopustular eruption during the 6 week skin treatment within Bepanthen and Cetomacrogol, as measured by the CTCAE v4.0 and DERETT-H, an dermatologic specific healthcare provider questionnaire for Dermatological Reactions Targeted Therapy.	6 weeks
impact of papulopustular eruptions on HRQoL	Assess the impact of papulopustular eruptions on HRQoL as measured by the Functional Assessment of Cancer Therapy Questionnaire - EGFRI (FACT-EGFRI) and newly developed symptom experience diary Dermatological Reactions Targeted Therapy - Patients (DERETT-P).	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
patient tolerability and satisfaction of study cream	Determine the patient tolerability and satisfaction of Bepanthen®/ Cetomacrogol cream as measured by DERETT-P.	6 weeks
effectiveness of study cream on the adherence	Determine the effectiveness of Bepanthen® cream versus Cetomacrogol cream on the adherence to anticancer agents as measured by FACT-EGFRI and DERETT-P.	6 weeks
other dermatological side effects	Assessments during the 6-week skin treatment period of the incidence and time to onset of other dermatological side effects which can appear together with papulopustular eruptions as measured by DERETT-H.	6 weeks

Collaborators and Investigators

• Sponsor: Impaqtt Foundation
• Collaborators: Memorial Sloan Kettering Cancer Center; Bayer; Leiden University Medical Center; CB Boers ORG
• Investigators: Study Chair: Christine Boers-Doets, MSc, Waterland Hospital, Purmerend, the Netherlands; Principal Investigator: Mario Lacouture, MD, Memorial Sloan-Kettering Cancer Center, USA; Principal Investigator: Johan Nortier, PhD, Leiden University Medical Centre, The Netherlands

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: June 2, 2010
• First Submitted That Met QC Criteria: June 2, 2010
• First Posted (Estimate): June 3, 2010

Study Record Updates

• Last Update Posted (Actual): November 13, 2017
• Last Update Submitted That Met QC Criteria: November 8, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: quality of life; adherence; receptor, epidermal growth factor; skin reactions
• Additional Relevant MeSH Terms: Skin Diseases; Exanthema; Physiological Effects of Drugs; Micronutrients; Vitamins; Provitamins
• Other Study ID Numbers: Impaqtt-001; M010-025 (Other Identifier: Medical research ethics committee: METC Noord Holland)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No