Display again
SNCTP000002443 | NCT02631447 | BASEC2017-00757

Prospektive, dreiarmige, Phase-II-Studie mit Behandlungszuteilung nach Zufallsprinzip zur Untersuchung des besten aufeinander folgenden Ansatzes der kombinierten Immuntherapie (Ipilimumab/Nivolumab) und der kombinierten zielgerichteten Krebstherapie (LGX818/MEK162) bei Patienten mit streuendem schwarzem Hautkrebs mit krankhafter Veränderung des BRAF-Gens

Data source: BASEC (Imported from 27.01.2022), WHO (Imported from 18.01.2022)
Changed: 14.01.2022
Disease category: Melanoma

Brief description of trial (Data source: BASEC)

In dieser internationalen Studie werden insgesamt 230 Patienten in ungefähr 30 Studienzentren in Europa und der Schweiz für diese Studie rekrutiert. In der Schweiz sollen ca. 10 Patienten in 1 Prüfzentrum eingeschlossen werden.

Die Dauer der Studie pro Patient hängt davon ab, ob Ihre Krankheit fortschreitet oder nicht. Sie werden solange behandelt bis ein Fortschreiten Ihrer Krankheit diagnostiziert wird oder Sie aufgrund anderer Gründe nicht mehr teilnehmen können, z.B. schwere Nebenwirkungen oder Ihr Wunsch, die Studie abzubrechen. Danach werden Sie mindestens 2 Jahre lang nachbeobachtet.
Im Rahmen Ihrer Krebserkrankung besuchen Sie schon jetzt regelmässig das Spital für Untersuchungen und Therapien. Durch die Teilnahme an dieser Studie werden diese Besuche allenfalls häufiger. Wie häufig, hängt von der Kombinationstherapie ab, welche Sie gerade erhalten. Im Durchschnitt sind sie alle 2 – 4 Wochen im Spital. Die Medikamente LGX818 und MEK162 sind Tabletten bzw. Kapseln und werden von Ihnen zuhause eingenommen. Die Medikamente Nivolumamb und Ipiliumab sind Infusionen, die in die Vene verabreicht werden und daher im Spital gegeben werden. Die Infusionen dauern zwischen 1 – 2.5 Stunden. Je nach Visite werden unterschiedliche Untersuchungen durchgeführt. Bei jeder Visite auf jeden Fall: körperliche Untersuchung, Vitalzeichen, ECOG-Leistungsstatus (Fragebogen), Blutuntersuchung, Erfassung aller Begleitmedikamente, Erfassung aller Nebenwirkungen. Zusätzlich werden eventuell durchgeführt: eine Computertomographie oder eine Magnetresonanztomographie, ein Elektrokardiogramm (zur Aufzeichnung der Herztöne), eine Echokardiographie (Herzuntersuchung mit Ultraschall), Farbfotographien Ihrer Tumorstellen am Körper, haut- und augenärztliche Untersuchungen, eine Urinuntersuchung, ein Schwangerschaftstest bei Frauen im gebärfähigen Alter, das Ausfüllen weiterer Fragebögen zur Lebensqualität. Ferner werden Sie gebeten, ein Medikamententagebuch zu führen.

Health conditions investigated (Data source: BASEC)

Schwarzer Hautkrebs (Melanom) mit Mutation de BRAF-Gens (Mutation: krankhafte Veränderungen in der DNA, dem genetischen Material der Körperzellen)

Health conditions (Data source: WHO)

Metastatic Melanoma

Rare disease (Data source: BASEC)

No

Intervention investigated (e.g. drug, therapy or campaign) (Data source: BASEC)

Die Studie untersucht die Wirkung der aufeinander folgenden Anwendung zweier unterschiedlicher Kombinationen von Arzneimitteln. Dabei gibt es drei Therapieansätze und es soll herausgefunden werden, welcher der drei der beste Ansatz für Patienten mit schwarzem Hautkrebs ist, bei denen der Krebs schon gestreut (metastasiert) hat und bei welchen ein Test die BRAF-Genmutation ergeben hat.
In der Studie kommen vier Medikamente zum Einsatz, die jeweils in zwei Kombinationen angewendet werden. Sie werden im Zufallsprinzip einem von 3 Studienarmen zugewiesen. Die Medikamente LGX818 und MEK162 sind in der Schweiz nicht zugelassen. Die Medikamente Nivolumab (Handelsname: Opdivo®) und Ipiliumab (Handelsname: Yervoy®) sind in der Schweiz zugelassen.

Interventions (Data source: WHO)

Drug: LGX818;Drug: MEK162;Drug: Nivolumab;Drug: Ipilimumab

Criteria for participation in trial (Data source: BASEC)

- Männliche oder weibliche Patienten älter als 18 Jahre
- Mittels Gewebeentnahme bestätigter schwarzer Hautkrebs Stadium III (inoperabel) oder Stadium IV mit BRAF-V600 Mutation
- Unbehandelte (naive) Patienten bezüglich metastasiernder Erkrankung.

Exclusion criteria (Data source: BASEC)

- Aktive Metastasen (Krebsableger) im Gehirn
- Patienten mit einer Autoimmunerkrankung
- Patienten, bei denen eine Behandlung mit Kortikosteroiden oder anderen Arzneimitteln, welche das Immunssystem unterdrücken notwendig ist
- Schwangere/stillende Frauen

Inclusion/Exclusion Criteria (Data source: WHO)


Inclusion Criteria:

1. Patients of either sex aged = 18 years;

2. Histologically confirmed stage III (unresectable) or stage IV melanoma with the BRAF
V600 mutation. Patients with mucosal melanoma (but not those with ocular melanoma) are
eligible for study participation;

3. Treatment naïve for metastatic disease patients. Previous adjuvant treatment, included
checkpoint inhibitors anti CTLA-4, anti PD-1/PDL-1 is allowed, except for stage IV (if
completed at least 6 weeks prior to randomization, and all related adverse events have
either returned to baseline or stabilized). BRAF inhibitor treatment in adjuvant
setting is not permitted.

4. Measurable disease by computed tomography (CT) or Magnetic Resonance Imaging (MRI) per
RECIST 1.1 criteria;

5. Presence of BRAF V600E or V600K mutation in tumor tissue prior to enrollment;

6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1;

7. Tumor tissue from an unresectable or metastatic site of disease must be provided for
biomarker analyses. An archive sample is mandatory at the screening visit; however, a
new sample collection would be preferable;

8. Female subjects of childbearing potential must have a negative pregnancy test result
at baseline and must practice two highly effective methods of contraception for the
total study duration plus 23 weeks (i.e. 30 days plus the time required for nivolumab
to undergo five half lives) after the last dose of nivolumab and ipilimumab and 30
days after the last dose of binimetinib and encorafenib for female subjects.
Additional pregnancy testing must be performed every 6 weeks during the treatment
Combo-Immuno and every 4 weeks during the treatment Combo-Target, as well as at the
end of the systemic exposure;

9. Men who are sexually active with women of childbearing potential must practice a
reliable method of contraception for the total study duration plus 31 weeks (i.e. 80
days plus the time required for nivolumab to undergo five half lives) after the last
dose of nivolumab and ipilimumab and 90 days after the last dose of binimetinib and
encorafenib;

10. Adequate bone marrow haematological function: absolute neutrophil count (ANC) = 1.5 x
109/L AND platelet count = 100 x 109/L AND haemoglobin = 9 g/dL;

11. Adequate liver function: total bilirubin = 1.5 x upper limit of normal (ULN) AND
aspartate aminotransferase (AST)/alanine aminotransferase (ALT) = 2.5 X ULN (< 5 x ULN
if liver metastases);

12. Adequate renal function: serum creatinine = 1.5 mg/dL OR creatinine clearance = 60
mL/min in males and = 50 mL/min in females (calculated according to Cockroft-Gault
formula);

13. Serum calcium levels, international normalised ratio (INR) and partial thromboplastin
time were within normal limits;

14. Life expectancy of at least 3 months;

15. Ability to understand study-related patient information and provision of written
informed consent for participation in the study.

16. Adequate electrolytes at Baseline, defined as serum potassium and magnesium levels
within institutional normal limits (Note: replacement treatment to achieve adequate
electrolytes will be allowed).

17. Adequate cardiac function:

- left ventricular ejection fraction (LVEF) = 50% as determined by a multigated
--acquisition (MUGA) scan or echocardiogram,

- QTc interval = 480 ms (preferably the mean from triplicate ECGs)

Exclusion Criteria:

1. Active brain metastases. Subjects with brain metastases are eligible if these have
been treated and there is no magnetic resonance imaging (MRI) evidence of progression
for at least 4 weeks after treatment is complete and within 28 days prior to first
dose of study drug administration. There must also be no requirement for
immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone
equivalents) for at least 2 weeks prior to study drug administration;

2. Subjects with active, known or suspected autoimmune disease;

3. Subjects with a condition requiring systemic treatment with either corticosteroids
(>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14
days of treatment;

4. Prior treatment for stage III (unresectable) or stage IV melanoma with an
anti-Programmed Death receptor-1 (PD-1), anti-Programmed Death-1 ligand-1 (PD-L1),
anti-PD-L2, or anti-cytotoxic T lymphocyte associated antigen-4 (anti-CTLA-4)
antibody;

5. Female subjects who are pregnant (positive pregnancy test), breast-feeding, or who are
of childbearing potential and not practicing a reliable method of birth control;

6. Evidence of severe or uncontrolled systemic disease or any concurrent condition which
in the investigator's opinion makes it undesirable for the patient to participate in
the study, or which would jeopardize compliance with the protocol, or would interfere
with the results of the study;

7. Patients with a history of uncontrolled cardiovascular or interstitial lung disease
and evidence or risk of retinal vein occlusion or central serous retinopathy (patients
with a history of cardiovascular or interstitial lung disease and evidence or risk of
retinal vein occlusion or central serous retinopathy (past or present evidence of
rethinophaty central serous retinopathy - CSR -, occlusion of retinal - RVOo retinal
degenerative disease) or ophthalmopathy, which according to the ophthalmologic
evaluation at baseline could be considered a risk factor for CSR / RVO ( eg. cupping
of the optic disc, visual field defect, intraocular pressure - (eg: central IOP - > 21
mmHg);

8. Previous or concurrent malignancy. Exceptions: adequately treated basal cell or
squamous cell skin cancer; in situ carcinoma of the cervix, treated curatively and
without evidence of recurrence for at least 3 years prior to study entry; or other
solid tumor treated curatively, and without evidence of recurrence for at least 3
years prior to study entry

9. History of Gilbert's syndrome;

10. Inability to regularly access centre facilities for logistical or other reasons;

11. History of poor co-operation, non-compliance with medical treatment, or unreliability;

12. Participation in any interventional drug or medical device study within 30 days prior
to treatment start.

13. Positive test for human immunodeficiency virus (HIV), hepatitis B virus surface
antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating
acute or chronic in

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/show/NCT02631447

Further information on the trial from WHO database (ICTRP)

https://trialsearch.who.int/Trial2.aspx?TrialID=NCT02631447

Further information on trial

Date trial registered

09.12.2015

Incorporation of the first participant

14.11.2016

Recruitment status

Active, not recruiting

Academic title (Data source: WHO)

A Three Arms Prospective, Randomized Phase II Study to Evaluate the Best Sequential Approach With Combo Immunotherapy (Ipilimumab/Nivolumab) and Combo Target Therapy (LGX818/MEK162) in Patients With Metastatic Melanoma and BRAF Mutation

Type of trial (Data source: WHO)

Interventional

Design of the trial (Data source: WHO)

Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Phase (Data source: WHO)

Phase 2

Primary end point (Data source: WHO)

Overall Survival

Secundary end point (Data source: WHO)

Total Progression free survival;Percentage of patients alive at 2 and 3 years;Best overall response rate (BORR);Duration of response (DoR);Toxicity of the investigational medicinal products (IMPs).;Quality of life and general health;3 years PFS rate

Contact information (Data source: WHO)

Please refer to primary and secondary sponsors

Trial results (Data source: WHO)

Results summary

no information available yet

Link to the results in the primary register

no information available yet

Information on the availability of individual participant data

No

Trial sites

Trial sites in Switzerland (Data source: BASEC)

Zurich

Countries (Data source: WHO)

Austria, France, Germany, Greece, Italy, Poland, Spain, Sweden, Switzerland, United Kingdom

Contact for further information on the trial

Details of contact in Switzerland (Data source: BASEC)

Prof. Dr. med. Reinhard Dummer
044 255 25 88
reinhard.dummer@usz.ch

Contact for general information (Data source: WHO)

Paolo Ascierto, MD
Fondazione Melanoma Onlus

Contact for scientific information (Data source: WHO)

Paolo Ascierto, MD
Fondazione Melanoma Onlus

Principal Sponsor/Investigator

Principal sponsor (Data source: WHO)

Fondazione Melanoma Onlus

Additional sponsors (Data source: WHO)

Clinical Research Technology S.r.l.

Authorisation by the ethics committee (Data source: BASEC)

Name of the authorising ethics committee (for multicentre studies only the lead committee)

Kantonale Ethikkommission Zürich

Date of authorisation by the ethics committee

31.07.2017

Further trial identification numbers

Trial identification number of the ethics committee (BASEC-ID) (Data source: BASEC)

2017-00757

Secondary ID (Data source: WHO)

2014-004842-92
SECOMBIT