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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01597908




Registration number
NCT01597908
Ethics application status
Date submitted
10/05/2012
Date registered
14/05/2012

Titles & IDs
Public title
Dabrafenib Plus Trametinib vs Vemurafenib Alone in Unresectable or Metastatic BRAF V600E/K Cutaneous Melanoma
Scientific title
A Phase III, Randomised, Open-label Study Comparing the Combination of the BRAF Inhibitor, Dabrafenib and the MEK Inhibitor, Trametinib to the BRAF Inhibitor Vemurafenib in Subjects With Unresectable (Stage IIIc) or Metastatic (Stage IV) BRAF V600E/K Mutation Positive Cutaneous Melanoma
Secondary ID [1] 0 0
CDRB436B2302
Secondary ID [2] 0 0
116513
Universal Trial Number (UTN)
Trial acronym
COMBI-v
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

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

Experimental: Dabrafenib plus Trametinib - BRAF inhibitor plus MEK inhibitor

Active comparator: Vemurafenib - BRAF inhibitor


Treatment: Drugs: Dabrafenib
Dabrafenib 150 mg twice daily orally

Treatment: Drugs: Vemurafenib
Vemurafenib 960 mg twice daily orally

Treatment: Drugs: Trametinib
Trametinib 2 mg once daily orally
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From the date of randomization until date of death due to any cause (up to approximately 6 years)
Secondary outcome [1] 0 0
Progression-Free Survival (PFS), as Assessed by the Investigator
Timepoint [1] 0 0
From randomization until the earliest date of disease progression (PD) or death due to any cause (up to approximately 6 years)
Secondary outcome [2] 0 0
Overall Response Rate (ORR) During Randomized Phase, as Assessed by the Investigator
Timepoint [2] 0 0
From randomization until the first documented complete response or partial response (up to approximately 6 years)
Secondary outcome [3] 0 0
Duration of Response (DOR), as Assessed by the Investigator
Timepoint [3] 0 0
From the time of the first documented response (CR or PR) until disease progression (up to approximately 6 years)

Eligibility
Key inclusion criteria
Key

* >= 18 years of age
* Stage IIIc or Stage IV BRAF V600E/K cutaneous melanoma
* Measurable disease according to RECIST 1.1
* Women of childbearing potential with negative serum pregnancy test prior to randomisation
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Adequate baseline organ function

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Any prior use of a BRAF or MEK inhibitor
* Prior systemic anti-cancer treatment in the advanced or metastatic setting; prior systemic treatment in the adjuvant setting is allowed
* History of another malignancy (except subjects who have been disease free for 3 years or with a history of completely resected non-melanoma skin cancer)
* Known HIV, HBV, HCV infection (except chronic or cleared HBV and HCV infection which will be allowed)
* Brain metastases (except if all known lesions were previously treated with surgery or stereotactic radiosurgery and lesions, if still present, are confirmed stable for >= 12 weeks prior to randomisation or if no longer present are confirmed no evidence of disease for >= 12 weeks, and are asymptomatic with no corticosteroid requirements for >= 4 weeks prior to randomisation, and no enzyme inducing anticonvulsants for >= 4 weeks prior to randomisation
* History or evidence of cardiovascular risk (LVEF < LLN; QTcB >= 480 msec; blood pressure or systolic >=140 mmHg or diastolic >= 90 mmHg which cannot be controlled by anti-hypertensive therapy)
* History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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
Parallel
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
4/06/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
25/04/2019
Sample size
Target
Accrual to date
Final
704
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - North Sydney
Recruitment hospital [2] 0 0
Novartis Investigative Site - Westmead
Recruitment hospital [3] 0 0
Novartis Investigative Site - Greenslopes
Recruitment hospital [4] 0 0
Novartis Investigative Site - Herston
Recruitment hospital [5] 0 0
Novartis Investigative Site - South Brisbane
Recruitment hospital [6] 0 0
Novartis Investigative Site - Woodville
Recruitment hospital [7] 0 0
Novartis Investigative Site - Box Hill
Recruitment hospital [8] 0 0
Novartis Investigative Site - Melbourne
Recruitment hospital [9] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
2060 - North Sydney
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4120 - Greenslopes
Recruitment postcode(s) [4] 0 0
4029 - Herston
Recruitment postcode(s) [5] 0 0
4101 - South Brisbane
Recruitment postcode(s) [6] 0 0
5011 - Woodville
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3128 - Box Hill
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3004 - Melbourne
Recruitment postcode(s) [9] 0 0
6009 - Nedlands
Recruitment outside Australia
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Alabama
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Hospitalet de Llobregat, Barcelona
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Kharkiv
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Kyiv
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Lviv
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Ukraine
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Sumy
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Uzhgorod
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Manchester
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Southampton
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United Kingdom
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Swansea

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?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT01597908