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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT03551626
Registration number
NCT03551626
Ethics application status
Date submitted
30/04/2018
Date registered
11/06/2018
Date last updated
18/03/2024
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
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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)
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Secondary ID [1]
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2018-000168-27
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Secondary ID [2]
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CDRB436F2410
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Universal Trial Number (UTN)
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Trial acronym
COMBI-APlus
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Malignant Melanoma
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Condition category
Condition code
Cancer
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Malignant melanoma
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Injuries and Accidents
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0
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Other injuries and accidents
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Intervention/exposure
Study type
Interventional
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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
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Composite Rate of Pyrexia Related Events
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Assessment method [1]
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The composite rate of pyrexia related events was calculated as the total number of participants experiencing at least one of the three components of the composite endpoint (i.e., grade 3/4 pyrexia, hospitalization due to pyrexia, or permanent treatment discontinuation due to pyrexia), divided by the total number of participants treated in the study and multiplied by 100. Pyrexia is defined as fever = 38 °C.
Pyrexia events were graded by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (Life-threatening) and Grade 5 (Death)
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Timepoint [1]
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Baseline up to 12 months
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Secondary outcome [1]
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Relapse Free Survival (RFS) Rate
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Assessment method [1]
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RFS is defined as the time from the date of first dose of the study treatment to the date of the first documented disease recurrence or death due to any cause whichever comes first. Treatment emergent malignancies other than second melanomas were not considered as events.
RFS rate is the estimated percent probability that a patient will remain event-free up to the specified time point. RFS rate was obtained from the Kaplan-Meier survival estimates. RFS was censored if no RFS event was observed before the first to occur between: (i) the analysis cut-off date, and (ii) the date when a new anti-cancer therapy is started. The censoring date was the date of the last adequate tumor assessment prior to data cut-off date/start of new anti-cancer therapy date.
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Timepoint [1]
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At 12 and 24 months
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Secondary outcome [2]
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Overall Survival (OS) Rate
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Assessment method [2]
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OS is defined as the time from date of the first dose of study medication to date of death due to any cause, whichever comes first. If a patient was not known to have died, then OS rate is the estimated probability that a patient will remain event-free up to the specified time point. OS rate was obtained from the Kaplan-Meier survival estimates. OS was censored at the last contact date when the patient was known to be alive (on or before the cut-off date).
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Timepoint [2]
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At 12 and 24 months
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Secondary outcome [3]
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Percentage of Participants Who Required Management of Pyrexia
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Assessment method [3]
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Percentage of patients who experienced pyrexia and required intervention including hospitalizations, concomitant medications, and study treatment modifications (dose reductions, permanent discontinuations and/or interruptions) due to pyrexia. Pyrexia is defined as fever = 38 °C
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Timepoint [3]
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Baseline up to 12 months
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Secondary outcome [4]
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Percentage of Participants Who Permanently Discontinued Treatment Due to Any Adverse Event (AE)
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Assessment method [4]
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Percentage of participants who permanently discontinued treatment due to any AE during treatment. An AE is any untoward medical occurrence (e.g., any unfavorable and unintended sign, symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study.
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Timepoint [4]
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Baseline up to 12 months
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Secondary outcome [5]
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Change From Baseline in Subject-reported Quality of Life (QoL) Assessed by Functional Assessment Cancer Therapy - Melanoma Subscale Score (FACT-M MS)
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Assessment method [5]
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The FACT-M is a questionnaire that assesses participant health-related quality of life. It includes a melanoma specific (FACT-M MS) subscale that consists in 16 items related to signs, symptoms, physical/social activities most relevant to participants with advanced-stage melanoma. Each item ranges from 0 (not at all) to 4 (very much). FACT-M MS score ranges from 0 to 64, with higher score indicating better quality of life. If a patient discontinued the study treatment at Month 1 or Month 2, then the follow-up assessments started at Month 3 follow-up and continued until Month 24 follow-up or at withdrawal, lost to follow-up, death, or end of study. If a patient discontinued the study treatment from Month 3 through Month 5, the follow-up assessments started at Month 6 follow-up. If a patient discontinued from Month 6 through Month 11, the follow-up assessments started from Month 12 follow-up. For patients who completed treatment, the follow-up assessments started from Month 15 follow-up
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Timepoint [5]
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Baseline up to 24 months
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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
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
N/A
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
29/08/2018
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
16/09/2021
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Sample size
Target
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Accrual to date
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Final
552
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Recruitment in Australia
Recruitment state(s)
QLD
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Recruitment hospital [1]
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Novartis Investigative Site - Woolloongabba
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Recruitment hospital [2]
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Novartis Investigative Site - Cairns
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Recruitment postcode(s) [1]
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4102 - Woolloongabba
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Recruitment postcode(s) [2]
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QLD 4870 - Cairns
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Recruitment outside Australia
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Argentina
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Sante Fe
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Cordoba
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RJ
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Brazil
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Novartis Pharmaceuticals
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Ethics approval
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Summary
Brief summary
The main purpose of this study was to evaluate the impact on pyrexia-related outcomes of an
adapted pyrexia adverse event (AE)-management algorithm, as well as safety, efficacy and
health-related outcomes.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT03551626
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
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Novartis Pharmaceuticals
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Novartis Pharmaceuticals
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT03551626
Download to PDF