Study of Dabrafenib+Trametinib in the Adjuvant Treatment of Stage III BRAF V600+ Melanoma After Complete Resection to Evaluate the Impact on Pyrexia Related Outcomes

COMBI-APlus: Open-label, Phase IIIb Study of Dabrafenib in COMBInation With Trametinib in the Adjuvant Treatment of Stage III BRAF V600 Mutation-positive Melanoma After Complete Resection to Evaluate the Impact on Pyrexia Related Outcomes of an Adapted Pyrexia AE-management Algorithm (Plus)

ClinicalTrials.gov Identifier: NCT03551626

Novartis Reference Number: CDRB436F2410

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

This is an open-label Phase IIIb study of dabrafenib in combination with trametinib in the adjuvant treatment of melanoma after complete resection to evaluate the impact on pyrexia related outcomes of an adapted pyrexia AE-management algorithm, as well as safety, efficacy and health-related outcomes.

Approximately 600 subjects will be enrolled to receive dabrafenib (150 mg BID) and trametinib (2 mg once daily) combination therapy for 12 months. At enrollment, subjects will be instructed on the pyrexia management algorithm.

This study consists of two Periods for Enrolled subjects:

Treatment Period - subjects will receive up to 12 months of treatment.
Follow-up Period - subjects will be followed through 24 months from their first dose date for relapse, and through end of study for overall survival. Follow-up will start once treatment is complete or is prematurely discontinued and continue through the end of the study, regardless of disease recurrence.

Condition 
Malignant Melanoma
Phase 
Phase 3
Overall status 
Active, not recruiting
Enrollment count 
557 participants
Start date 
Aug 29, 2018
Completion date 
Oct 22, 2021
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
Dabrafenib
Supplied as dabrafenib 50 mg, 75 mg Capsules for oral use
Drug
Trametinib
supplied as trametinib 0.5mg, 2.0mg tablets for oral use

Eligibility Criteria

Inclusion Criteria:

Completely resected histologically confirmed cutaneous melanoma stage IIIA (LN metastasis >1 mm), IIIB, IIIC, IIID [AJCC (ed 8)]
V600E/K mutation positive using a validated local test
Subjects presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible.
Subjects who have previously had Stage III melanoma at any time are not eligible.
Recovered from definitive surgery (e.g. no uncontrolled wound infections or indwelling drains).
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1

Exclusion Criteria:

Uveal or mucosal melanoma
Evidence of metastatic disease including unresectable in-transit metastasis
Received any prior adjuvant or neoadjuvant treatment, including but not limited to chemotherapy, checkpoint inhibitors, targeted therapy [e.g., BRAF and/or MEK inhibitors], biologic therapy, vaccine therapy, investigational treatment, or radiotherapy for melanoma
Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers and any completely resected carcinoma in situ
History or current evidence of cardiovascular risk
A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy

Study Locations

Argentina
Novartis Investigative Site
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Rosario, S200KZE
Sante Fe
Argentina
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Buenos Aires, C1125ABE
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Argentina
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Cordoba, X5004BAL
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Argentina
Australia
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Woolloongabba, 4102
Queensland
Australia
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Cairns, QLD 4870
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Australia
Brazil
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Rio de Janeiro, 20220410
RJ
Brazil
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Porto Alegre, 90035-003
RS
Brazil
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Sao Paulo, 01246 000
SP
Brazil
Canada
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Calgary, T2N 4N2
Alberta
Canada
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Edmonton, T6G 1Z2
Alberta
Canada
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Hamilton, L8V 5C2
Ontario
Canada
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London, N6A 4L6
Ontario
Canada
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Ottawa, K1H 8L6
Ontario
Canada
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Toronto, M4N 3M5
Ontario
Canada
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Toronto, M5G 1Z6
Ontario
Canada
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Montreal, H3T 1E2
Quebec
Canada
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Quebec, G1R 2J6
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Canada
Czechia
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Brno, 656 53
Czech Republic
Czechia
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Ostrava Poruba, 708 52
Czech Republic
Czechia
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Prague 8, 180 00
Czech Republic
Czechia
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Zlin, 762 75
Czech Republic
Czechia
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Hradec Kralove, 500 05
CZE
Czechia
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Prague, 11000
Prague 1
Czechia
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Olomouc, 775 20
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Czechia
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Praha, 12808
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Czechia
Finland
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Helsinki, 9
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Finland
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Tampere, FIN-33521
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Finland
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Turku, 20520
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Finland
France
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Pierre Benite Cedex, 69495
Cedex 02
France
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Limoges cedex, 87000
Haute Vienne
France
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Rennes Cedex, 35062
Ille Et Vilaine
France
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Besancon Cedex, 25030
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France
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Bobigny Cedex, 93009
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France
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Bordeaux Cedex, 33075
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France
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Boulogne Billancourt, 92104
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France
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Clermont Ferrand cedex 1, 63003
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France
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Dijon, 21034
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France
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Grenoble Cedex 9, 38043
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France
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Lille Cedex, 59037
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France
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Lorient Cedex, 56322
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France
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Marseille Cedex 9, 13913
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France
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Montpellier, 34295
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France
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Nice, 06202
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France
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Paris Cedex 10, 75475
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France
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Poitiers, 86021
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France
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Reims, 51092
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France
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Toulouse Cedex 9, 31059
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France
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Villejuif Cedex, 94800
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France
Greece
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Athens, 115 27
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Greece
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Athens, 18547
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Greece
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Athens, GR 115 22
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Greece
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Thessaloniki, 54622
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Greece
Hungary
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Budapest, H 1122
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Hungary
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Pecs, 7632
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Hungary
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Szeged, H 6725
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Hungary
Israel
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Jerusalem, 91120
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Israel
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Ramat Gan, 52621
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Israel
Italy
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Bergamo, 24127
BG
Italy
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Meldola, 47014
FC
Italy
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Antella - Bagno A Ripoli, 50011
FI
Italy
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Genova, 16132
GE
Italy
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Milano, 20133
MI
Italy
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Milano, 20141
MI
Italy
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Modena, 41124
MO
Italy
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Palermo, 90127
PA
Italy
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Padova, 35100
PD
Italy
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Roma, 00128
RM
Italy
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Roma, 00167
RM
Italy
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Torino, 10126
TO
Italy
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Udine, 33100
UD
Italy
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Napoli, 80131
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Italy
Japan
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Sapporo-city, 060-8543
Hokkaido
Japan
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Chuo ku, 104 0045
Tokyo
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Latvia
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Riga, LV 1079
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Latvia
Lithuania
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Vilnius, LT-08660
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Lithuania
Norway
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Oslo, 0379
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Norway
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Ålesund, NO-6026
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Norway
Poland
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Gdansk, 80 952
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Poland
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Warszawa, 02 781
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Poland
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Wroclaw, 53 413
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Poland
Portugal
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Porto, 4200-072
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Portugal
Russian Federation
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Moscow, 115478
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Russian Federation
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Moscow, 143423
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Russian Federation
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Omsk, 644013
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Russian Federation
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St Petersburg, 197758
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Russian Federation
Slovakia
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Bratislava, 812 50
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Slovakia
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Kosice, 04191
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Slovakia
Slovenia
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Ljubljana, 1000
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Slovenia
Sweden
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Goteborg, SE-413 45
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Sweden
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Orebro, 701 85
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Sweden
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Stockholm, SE 171 76
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Sweden
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Umea, SE 901 85
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Sweden
Turkey
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Izmir, 35040
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Turkey
United Kingdom
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Bristol, BS2 8ED
Avon
United Kingdom
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Northwood, HA6 2RN
Middlesex
United Kingdom
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Sheffield, S10 2JF
South Yorkshire
United Kingdom
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Cambridge, CB2 2QQ
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United Kingdom
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Leeds, LS9 7TF
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United Kingdom
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Manchester, M20 9BX
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United Kingdom
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Southampton, SO16 6YD
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United Kingdom

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