Binimetinib Plus Encorafenib Real Life Investigation of Next Generation Melanoma Treatment

Melanoma Stage IV Clinical Trial

— BERING  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04045691
• Other study ID #: NIS-PFO-2019-1921
• Status: Recruiting
• Start date: October 17, 2019
• Est. completion date: September 2027

Study information

• Verified date: January 2021
• Source: Pierre Fabre Pharma GmbH
• Contact: Christian A Rosé, MD
• Phone: +49 761 45261
• Email: bering_de[@]pierre-fabre.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 750
• Est. completion date: September 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Melanoma
• Melanoma Stage III
• Melanoma Stage IV

Intervention

Drug:
• Encorafenib
Observation of real-life treatment with encorafenib and binimetinib
• Binimetinib
Observation of real-life treatment with encorafenib and binimetinib

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
Pierre Fabre Pharma GmbH	Pierre Fabre Pharma AG, Pierre Fabre Pharma Austria

Countries where clinical trial is conducted

Austria,  Germany,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival	Progression-free survival rate	At 12 months after start of treatment
Secondary	Patient and disease profiles at start of treatment with encorafenib plus binimetinib	Demographic and disease characteristics	Baseline
Secondary	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).
Secondary	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).
Secondary	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)
Secondary	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)
Secondary	Effectiveness of treatment with encorafenib plus binimetinib	Time-to-progression	From start to end of treatment (anticipated median treatment duration ca. 12 months)
Secondary	Effectiveness of treatment with encorafenib plus binimetinib	Best observed tumor response	From start to end of treatment (anticipated median treatment duration ca. 12 months)
Secondary	Effectiveness of treatment with encorafenib plus binimetinib	Overall response rate	From start to end of treatment (anticipated median treatment duration ca. 12 months)
Secondary	Effectiveness of treatment with encorafenib plus binimetinib	Duration of response	From start to end of treatment (anticipated median treatment duration ca. 12 months)
Secondary	Effectiveness of treatment with encorafenib plus binimetinib	Disease control rate	From start to end of treatment (anticipated median treatment duration ca. 12 months)
Secondary	Effectiveness of treatment with encorafenib plus binimetinib	Duration of disease control	From start to end of treatment (anticipated median treatment duration ca. 12 months)
Secondary	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).
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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).
Secondary	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).
Secondary	Prognostic factors	Influence of prognostic factors on effectiveness	Complete observation time-frame (the total observation period of this study will amount to 90 months).
Secondary	Prognostic factors	Influence of prognostic factors on safety	Complete observation time-frame (the total observation period of this study will amount to 90 months).
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)