Binimetinib Plus Encorafenib Real Life Investigation of Next Generation Melanoma Treatment (BERING)

Encorafenib Plus Binimetinib in Patients With Locally Advanced, Unresectable or Metastatic BRAFV600-mutated Melanoma: a Multi-centric, Multinational, Prospective, Longitudinal, Non-interventional Study in Germany, Austria and Switzerland - BERING MELANOMA

BERING-MELANOMA - designed as a prospective, longitudinal, non-interventional study - investigates real-world effectiveness, quality of life, safety and tolerability of encorafenib plus binimetinib in unresectable advanced or metastatic BRAF(Rapidly Accelerated Fibrosarcoma isoform B)-V600-mutant malignant melanoma after commercial availability of these two products in Germany, Austria and Switzerland. The study focusses on the documentation of the first and second line setting (i.e. after one line of prior checkpoint inhibition) by documenting patients treated according to the SmPC (Summary of Product Characteristics).

Study Overview

• Status: Recruiting
• Conditions: Melanoma Stage IV; Melanoma Stage III
• Intervention / Treatment: Drug: Encorafenib; Drug: Binimetinib

• Study Type: Observational
• Enrollment (Anticipated): 750

Contacts and Locations

• Study Contact: Name: Christian A Rosé, MD; Phone Number: +49 761 45261; Email: bering_de@pierre-fabre.com
• Study Contact Backup: Name: Andrea Schmidt, MSc; Phone Number: +49 641 94436; Email: ansc@alcedis.de

Study Locations

• Austria
  • Graz, Austria
    • Recruiting
    • 11
  • Innsbruck, Austria
    • Recruiting
    • 13
  • Klagenfurt, Austria
    • Recruiting
    • 14
  • Linz, Austria
    • Recruiting
    • 10
  • Linz, Austria
    • Recruiting
    • 3
  • Salzburg, Austria
    • Recruiting
    • 12
  • Wien, Austria
    • Recruiting
    • 22
  • Wien, Austria
    • Recruiting
    • 53
  • Wiener Neustadt, Austria
    • Recruiting
    • 23
• Germany
  • Ahaus, Germany
    • Recruiting
    • 45
  • Aschaffenburg, Germany
    • Recruiting
    • 8
  • Augsburg, Germany
    • Recruiting
    • 56
  • Berlin, Germany
    • Recruiting
    • 51
  • Bremerhaven, Germany
    • Recruiting
    • 27
  • Buxtehude, Germany
    • Recruiting
    • 1
  • Chemnitz, Germany
    • Recruiting
    • 43
  • Donauwörth, Germany
    • Recruiting
    • 34
  • Dresden, Germany
    • Recruiting
    • 49
  • Duisburg, Germany
    • Recruiting
    • 47
  • Erfurt, Germany
    • Recruiting
    • 40
  • Essen, Germany
    • Recruiting
    • 20
  • Gera, Germany
    • Recruiting
    • 9
  • Gießen, Germany
    • Recruiting
    • 28
  • Goslar, Germany
    • Recruiting
    • 42
  • Göttingen, Germany
    • Recruiting
    • 59
  • Hamburg, Germany
    • Recruiting
    • 19
  • Hannover, Germany
    • Recruiting
    • 21
  • Heidelberg, Germany
    • Recruiting
    • 2
  • Karlsruhe, Germany
    • Recruiting
    • 33
  • Kiel, Germany
    • Recruiting
    • 39
  • Landshut, Germany
    • Recruiting
    • 29
  • Leipzig, Germany
    • Recruiting
    • 44
  • Ludwigshafen, Germany
    • Recruiting
    • 30
  • Lübeck, Germany
    • Recruiting
    • 4
  • Magdeburg, Germany
    • Recruiting
    • 46
  • Mainz, Germany
    • Recruiting
    • 15
  • Mannheim, Germany
    • Recruiting
    • 5
  • Marburg, Germany
    • Recruiting
    • 57
  • Minden, Germany
    • Recruiting
    • 6
  • München, Germany
    • Recruiting
    • 31
  • München, Germany
    • Recruiting
    • 7
  • Münster, Germany
    • Recruiting
    • 16
  • Münster, Germany
    • Recruiting
    • 35
  • Nürnberg, Germany
    • Recruiting
    • 18
  • Regensburg, Germany
    • Recruiting
    • 50
  • Schorndorf, Germany
    • Recruiting
    • 41
  • Schwerin, Germany
    • Recruiting
    • 17
  • Stolberg, Germany
    • Recruiting
    • 48
  • Trier, Germany
    • Recruiting
    • 55
  • Tübingen, Germany
    • Recruiting
    • 54
  • Zwickau, Germany
    • Recruiting
    • 32
• Switzerland
  • Aarau, Switzerland
    • Recruiting
    • 38
  • Bern, Switzerland, 3010
    • Recruiting
    • 37
  • Chur, Switzerland
    • Recruiting
    • 24
  • Lausanne, Switzerland
    • Recruiting
    • 36
  • Luzern, Switzerland, 6000
    • Recruiting
    • 58
  • Winterthur, Switzerland
    • Recruiting
    • 26
  • Zürich, Switzerland
    • Recruiting
    • 25
  • Tessin
    • Bellinzona, Tessin, Switzerland, 6500
      • Recruiting
      • 52

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with unresectable advanced or metastatic BRAFV600-mutant malignant melanoma, with a decision to receive targeted treatment with Encorafenib/Binimetinib according to the current SmPC.

Description

Inclusion Criteria:

• Written informed consent of the patient with regard to the pseudonymized documentation as well as the transfer and processing of his/her data within the study and the ADOREG [Cancer Registry of German Working Group of Dermato-Oncology] registry (data transfer to ADOREG registry only for patients from German sites);
• Legally capable male or female patient ≥ 18 years of age (no upper limit);
• Decision was taken to treat the patient with encorafenib plus binimetinib in accordance with the current SmPC [Summary of Product Characteristics] and by prescription; this decision was taken prior to and independent from the inclusion into the study;
• Treatment with encorafenib plus binimetinib has been started ≤ 6 months prior to providing written informed consent for this study or is planned to be started in the near future;
• Unresectable advanced or metastatic malignant melanoma with BRAF [Rapidly Accelerated Fibrosarcoma isoform B] V600 mutation;
• Treatment-naive or after one prior line of checkpoint inhibitor treatment (anti-CTLA4 [Cytotoxic T-Lymphocyte Antigen-4] and/or anti-PD(L)1 [Programmed cell Death protein 1]) in the unresectable advanced or metastatic setting.

Exclusion Criteria:

• Previous treatment with a BRAF- and/or MEK [Mitogen-Activated Protein/Extracellular-signal Regulated Kinase]- inhibitor except for:

  -- prior adjuvant treatment with BRAF+MEK-inhibitor combination therapy that ended > 6 months prior start of Encorafenib/Binimetinib treatment;

• More than one prior line of checkpoint inhibitor treatment in the unresectable advanced or metastatic setting;
• Any previous chemotherapeutic treatment of the melanoma disease;
• Presence of any contraindication with regard to the encorafenib-binimetinib-treatment as specified in the corresponding SmPCs;
• Current or upcoming participation in an interventional clinical trial;
• Current or upcoming systemic treatment of any other tumor than melanoma;
• Prisoners or persons who are compulsorily detained (involuntarily incarcerated).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Progression-free survival rate	At 12 months after start of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient and disease profiles at start of treatment with encorafenib plus binimetinib	Demographic and disease characteristics	Baseline
Type of treatments before and after encorafenib plus binimetinib	Treatment sequence prior to and after encorafenib plus binimetinib; by documenting pre-treatments with adjuvant therapy and systemic therapy in palliative setting; and by documenting subsequent systemic treatment lines after administration of encorafenib plus binimetinib	Complete observation time-frame (the total observation period of this study will amount to 90 months).
Sequence of treatments before and after encorafenib plus binimetinib	Treatment sequence prior to and after encorafenib plus binimetinib; by documenting pre-treatments with adjuvant therapy and systemic therapy in palliative setting; and by documenting subsequent systemic treatment lines after administration of encorafenib plus binimetinib	Complete observation time-frame (the total observation period of this study will amount to 90 months).
Characteristics of treatment with encorafenib plus binimetinib	Evaluation of reason for treatment selection (efficacy, safety profile, quality of life, patients preference, physician's preference, comorbidities, other)	From start to end of treatment (anticipated median treatment duration ca. 12 months)
Effectiveness of treatment with encorafenib plus binimetinib	Further progression-free survival parameters	From start to end of treatment (anticipated median treatment duration ca. 12 months)
Effectiveness of treatment with encorafenib plus binimetinib	Time-to-progression	From start to end of treatment (anticipated median treatment duration ca. 12 months)
Effectiveness of treatment with encorafenib plus binimetinib	Best observed tumor response	From start to end of treatment (anticipated median treatment duration ca. 12 months)
Effectiveness of treatment with encorafenib plus binimetinib	Overall response rate	From start to end of treatment (anticipated median treatment duration ca. 12 months)
Effectiveness of treatment with encorafenib plus binimetinib	Duration of response	From start to end of treatment (anticipated median treatment duration ca. 12 months)
Effectiveness of treatment with encorafenib plus binimetinib	Disease control rate	From start to end of treatment (anticipated median treatment duration ca. 12 months)
Effectiveness of treatment with encorafenib plus binimetinib	Duration of disease control	From start to end of treatment (anticipated median treatment duration ca. 12 months)
Effectiveness of treatment with encorafenib plus binimetinib	Overall survival	Complete observation time-frame (the total observation period of this study will amount to 90 months).
Patient reported outcomes during treatment with encorafenib plus binimetinib - evaluated with EORTC QLQ C-30	EORTC QLQ C-30 questionnaires (European Organisation for Research and Treatment of Cancer Quality of Life C-30 questionnaires) to assess quality of life of cancer patients; comprises 30 items, 24 of which are aggregated into nine multi-item scales, that is, five functioning scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain and nausea/vomiting) and one global health status scale. The remaining six single-item (dyspnoea, appetite loss, sleep disturbance, constipation, diarrhoea and the financial impact) scales assess symptoms.	From start to end of treatment (anticipated median treatment duration ca. 12 months)
Patient reported outcomes during treatment with encorafenib plus binimetinib evaluated with WPAI	WPAI questionnaires (Work Productivity and Activity Impairment questionnaires). The following questions ask about the effect of patients melanoma on the ability to work and perform regular activities.; Are you currently employed (working for pay)?; During the past seven days, how many hours did you miss from work because of problems associated with your melanoma?; During the past seven days, how many hours did you miss from work because of any other reason?; During the past seven days, how many hours did you actually work?; During the past seven days, how much did your melanoma affect your productivity while you were working?; During the past seven days, how much did your melanoma affect your ability to do your regular daily activities, other than work at a job?	From start to end of treatment (anticipated median treatment duration ca. 12 months)
Patient reported outcomes during treatment with encorafenib plus binimetinib evaluated with CTSQ	CTSQ questionnaires (Cancer Therapy Satisfaction Questionnaire) to assess patients' opinions and feelings concerning their cancer therapy and associated adverse events: Questions to patients thoughts about cancer therapy (IV/pills). Scale: [Always, Most of the time, Some-times, Rarely, Never];; Questions to patients satisfaction with the most recent cancer therapy (IV/pills):Scale reg. benefit: [Much better than my expectations Somewhat better than my expectations, Met my expectations, Somewhat worse than my expectations, Much worse than my expectations];Scale reg. side effects: [Much better than I expected, Somewhat better than I expected, Exactly as I expected, Somewhat worse than I expected, Much worse than I expected];Scale reg. satisfaction: [Very satisfied, Satisfied, Neither satisfied nor dissatisfied, Dissatisfied, Very dissatisfied];Scale reg. choice of therapy: [Yes, definitely, Probably Yes, I don't know, Probably not, Definitely not]	From start to end of treatment (anticipated median treatment duration ca. 12 months)
Physicians' satisfaction with regard the treatment with encorafenib plus binimetinib	Physicians' satisfaction questionnaires (measuring Physician's Satisfaction with regard to Effictiveness and Safety, as well as Physician's Overall Treatment Satisfaction) using the following scale construct: Physician's Satisfaction with regard to Efficiency; Physician's Satisfaction with regard to Safety; Physician's Overall Treatment Satisfaction Scale: very dissatisfied; dissatisfied; moderately satisfied; satisfied; very satisfied	From start to end of treatment (anticipated median treatment duration ca. 12 months)
Safety and tolerability of treatment with encorafenib plus binimetinib - Adverse events and adverse reactions including time to onset and time to resolution	Number of patients with Adverse Events and maximum grade per patient, Adverse Drug Reactions, Adverse Drug Reactions grade 3/4, Serious Adverse Events, Serious Adverse Drug Reactions.	Complete observation time-frame (the total observation period of this study will amount to 90 months).
Prognostic factors	Influence of prognostic factors on quality of life outcome parameters	Complete observation time-frame (the total observation period of this study will amount to 90 months).
Prognostic factors	Influence of prognostic factors on effectiveness	Complete observation time-frame (the total observation period of this study will amount to 90 months).
Prognostic factors	Influence of prognostic factors on safety	Complete observation time-frame (the total observation period of this study will amount to 90 months).
Treatment duration	From date of first treatment (encorafenib or binimetinib, whichever occurs first) until date of last treatment (encorafenib or binimetinib, whichever occurs last)	From start to end of treatment (anticipated median treatment duration ca. 12 months)
Treatment dose intensity	From date of first treatment (encorafenib or binimetinib, whichever occurs first) until date of last treatment (encorafenib or binimetinib, whichever occurs last)	From start to end of treatment (anticipated median treatment duration ca. 12 months)
Number of treatment interruptions	From date of first treatment (encorafenib or binimetinib, whichever occurs first) until date of last treatment (encorafenib or binimetinib, whichever occurs last)	From start to end of treatment (anticipated median treatment duration ca. 12 months)
Duration of treatment interruptions	From date of first treatment (encorafenib or binimetinib, whichever occurs first) until date of last treatment (encorafenib or binimetinib, whichever occurs last)	From start to end of treatment (anticipated median treatment duration ca. 12 months)

Collaborators and Investigators

• Sponsor: Pierre Fabre Pharma GmbH
• Collaborators: Pierre Fabre Pharma Austria; Pierre Fabre Pharma AG

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2019
• Primary Completion (Anticipated): December 1, 2026
• Study Completion (Anticipated): September 1, 2027

Study Registration Dates

• First Submitted: July 25, 2019
• First Submitted That Met QC Criteria: August 2, 2019
• First Posted (Actual): August 5, 2019

Study Record Updates

• Last Update Posted (Actual): January 19, 2021
• Last Update Submitted That Met QC Criteria: January 15, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: BERING; Encorafenib; Binimetinib
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: NIS-PFO-2019-1921

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
• product manufactured in and exported from the U.S.: No