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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03551626




Registration number
NCT03551626
Ethics application status
Date submitted
30/04/2018
Date registered
11/06/2018

Titles & IDs
Public title
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
Scientific title
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)
Secondary ID [1] 0 0
2018-000168-27
Secondary ID [2] 0 0
CDRB436F2410
Universal Trial Number (UTN)
Trial acronym
COMBI-APlus
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Injuries and Accidents 0 0 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dabrafenib
Treatment: Drugs - Trametinib

Experimental: Dabrafenib and trametinib combination therapy - Subjects received dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) orally for up to 12 months.


Treatment: Drugs: Dabrafenib
Supplied as dabrafenib 50 mg and 75 mg capsules for oral administration

Treatment: Drugs: Trametinib
Supplied as trametinib 0.5mg, and 2.0mg tablets for oral administration
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Composite Rate of Pyrexia Related Events
Timepoint [1] 0 0
Baseline up to 12 months
Secondary outcome [1] 0 0
Relapse Free Survival (RFS) Rate
Timepoint [1] 0 0
At 12 and 24 months
Secondary outcome [2] 0 0
Overall Survival (OS) Rate
Timepoint [2] 0 0
At 12 and 24 months
Secondary outcome [3] 0 0
Percentage of Participants Who Required Management of Pyrexia
Timepoint [3] 0 0
Baseline up to 12 months
Secondary outcome [4] 0 0
Percentage of Participants Who Permanently Discontinued Treatment Due to Any Adverse Event (AE)
Timepoint [4] 0 0
Baseline up to 12 months
Secondary outcome [5] 0 0
Change From Baseline in Subject-reported Quality of Life (QoL) Assessed by Functional Assessment Cancer Therapy - Melanoma Subscale Score (FACT-M MS)
Timepoint [5] 0 0
Baseline up to 24 months

Eligibility
Key inclusion criteria
Key

* Completely resected histologically confirmed cutaneous melanoma stage IIIA (LN metastasis >1 mm), IIIB, IIIC, IIID [AJCC (ed 8)] no more than 12 weeks, from last surgery, before Day 1

1. Subjects presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma were eligible.
2. Subjects who had previously had Stage III melanoma at any time were not eligible.
3. Recovered from definitive surgery (e.g. no uncontrolled wound infections or indwelling drains).
* V600E/K mutation positive using a validated local test
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 had 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 design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/08/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/09/2021
Sample size
Target
Accrual to date
Final
552
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Novartis Investigative Site - Woolloongabba
Recruitment hospital [2] 0 0
Novartis Investigative Site - Cairns
Recruitment postcode(s) [1] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 0 0
QLD 4870 - Cairns
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Sante Fe
Country [2] 0 0
Argentina
State/province [2] 0 0
Buenos Aires
Country [3] 0 0
Argentina
State/province [3] 0 0
Cordoba
Country [4] 0 0
Brazil
State/province [4] 0 0
RJ
Country [5] 0 0
Brazil
State/province [5] 0 0
RS
Country [6] 0 0
Brazil
State/province [6] 0 0
SP
Country [7] 0 0
Canada
State/province [7] 0 0
Alberta
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Canada
State/province [9] 0 0
Quebec
Country [10] 0 0
Czechia
State/province [10] 0 0
Czech Republic
Country [11] 0 0
Czechia
State/province [11] 0 0
CZE
Country [12] 0 0
Czechia
State/province [12] 0 0
Poruba
Country [13] 0 0
Czechia
State/province [13] 0 0
Prague 1
Country [14] 0 0
Czechia
State/province [14] 0 0
Olomouc
Country [15] 0 0
Czechia
State/province [15] 0 0
Praha
Country [16] 0 0
Finland
State/province [16] 0 0
Helsinki
Country [17] 0 0
Finland
State/province [17] 0 0
Tampere
Country [18] 0 0
Finland
State/province [18] 0 0
Turku
Country [19] 0 0
France
State/province [19] 0 0
Cedex 02
Country [20] 0 0
France
State/province [20] 0 0
Haute Vienne
Country [21] 0 0
France
State/province [21] 0 0
Ille Et Vilaine
Country [22] 0 0
France
State/province [22] 0 0
Besancon Cedex
Country [23] 0 0
France
State/province [23] 0 0
Bobigny Cedex
Country [24] 0 0
France
State/province [24] 0 0
Bordeaux Cedex
Country [25] 0 0
France
State/province [25] 0 0
Boulogne Billancourt
Country [26] 0 0
France
State/province [26] 0 0
Clermont Ferrand
Country [27] 0 0
France
State/province [27] 0 0
Dijon
Country [28] 0 0
France
State/province [28] 0 0
Grenoble Cedex 9
Country [29] 0 0
France
State/province [29] 0 0
Lille Cedex
Country [30] 0 0
France
State/province [30] 0 0
Lorient
Country [31] 0 0
France
State/province [31] 0 0
Marseille Cedex 05
Country [32] 0 0
France
State/province [32] 0 0
Montpellier
Country [33] 0 0
France
State/province [33] 0 0
Nice
Country [34] 0 0
France
State/province [34] 0 0
Paris 10
Country [35] 0 0
France
State/province [35] 0 0
Poitiers
Country [36] 0 0
France
State/province [36] 0 0
Reims
Country [37] 0 0
France
State/province [37] 0 0
Toulouse
Country [38] 0 0
France
State/province [38] 0 0
Villejuif
Country [39] 0 0
Greece
State/province [39] 0 0
Athens
Country [40] 0 0
Greece
State/province [40] 0 0
Thessaloniki
Country [41] 0 0
Hungary
State/province [41] 0 0
Budapest
Country [42] 0 0
Hungary
State/province [42] 0 0
Pecs
Country [43] 0 0
Hungary
State/province [43] 0 0
Szeged
Country [44] 0 0
Israel
State/province [44] 0 0
Jerusalem
Country [45] 0 0
Israel
State/province [45] 0 0
Ramat Gan
Country [46] 0 0
Italy
State/province [46] 0 0
BG
Country [47] 0 0
Italy
State/province [47] 0 0
FC
Country [48] 0 0
Italy
State/province [48] 0 0
FI
Country [49] 0 0
Italy
State/province [49] 0 0
GE
Country [50] 0 0
Italy
State/province [50] 0 0
MI
Country [51] 0 0
Italy
State/province [51] 0 0
MO
Country [52] 0 0
Italy
State/province [52] 0 0
PA
Country [53] 0 0
Italy
State/province [53] 0 0
PD
Country [54] 0 0
Italy
State/province [54] 0 0
RM
Country [55] 0 0
Italy
State/province [55] 0 0
TO
Country [56] 0 0
Italy
State/province [56] 0 0
UD
Country [57] 0 0
Italy
State/province [57] 0 0
Napoli
Country [58] 0 0
Japan
State/province [58] 0 0
Hokkaido
Country [59] 0 0
Japan
State/province [59] 0 0
Tokyo
Country [60] 0 0
Latvia
State/province [60] 0 0
Riga
Country [61] 0 0
Lithuania
State/province [61] 0 0
Vilnius
Country [62] 0 0
Norway
State/province [62] 0 0
Alesund
Country [63] 0 0
Norway
State/province [63] 0 0
Oslo
Country [64] 0 0
Poland
State/province [64] 0 0
Gdansk
Country [65] 0 0
Poland
State/province [65] 0 0
Warszawa
Country [66] 0 0
Poland
State/province [66] 0 0
Wroclaw
Country [67] 0 0
Portugal
State/province [67] 0 0
Porto
Country [68] 0 0
Russian Federation
State/province [68] 0 0
Moscow Region Istra Village
Country [69] 0 0
Russian Federation
State/province [69] 0 0
Moscow
Country [70] 0 0
Russian Federation
State/province [70] 0 0
Omsk
Country [71] 0 0
Russian Federation
State/province [71] 0 0
St Petersburg
Country [72] 0 0
Slovakia
State/province [72] 0 0
Bratislava
Country [73] 0 0
Slovakia
State/province [73] 0 0
Kosice
Country [74] 0 0
Slovenia
State/province [74] 0 0
Ljubljana
Country [75] 0 0
Sweden
State/province [75] 0 0
Goteborg
Country [76] 0 0
Sweden
State/province [76] 0 0
Orebro
Country [77] 0 0
Sweden
State/province [77] 0 0
Stockholm
Country [78] 0 0
Sweden
State/province [78] 0 0
Umea
Country [79] 0 0
Turkey
State/province [79] 0 0
Izmir
Country [80] 0 0
United Kingdom
State/province [80] 0 0
Avon
Country [81] 0 0
United Kingdom
State/province [81] 0 0
Middlesex
Country [82] 0 0
United Kingdom
State/province [82] 0 0
South Yorkshire
Country [83] 0 0
United Kingdom
State/province [83] 0 0
Cambridge
Country [84] 0 0
United Kingdom
State/province [84] 0 0
Leeds
Country [85] 0 0
United Kingdom
State/province [85] 0 0
Manchester
Country [86] 0 0
United Kingdom
State/province [86] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03551626