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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01682083




Registration number
NCT01682083
Ethics application status
Date submitted
6/09/2012
Date registered
10/09/2012
Date last updated
10/09/2019

Titles & IDs
Public title
Dabrafenib With Trametinib in the Adjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma (COMBI-AD).
Scientific title
COMBI-AD: A Phase III Randomized Double Blind Study of Dabrafenib (GSK2118436) in COMBInation With Trametinib (GSK1120212) Versus Two Placebos in the ADjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma After Surgical Resection
Secondary ID [1] 0 0
115532
Universal Trial Number (UTN)
Trial acronym
COMBI-AD
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 - Trametinib
Treatment: Drugs - Placebos

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

Placebo Comparator: Dabrafenib and trametinib placebos - Subjects received matching placebos orally for 12 months


Treatment: Drugs: Dabrafenib
Each capsule contained 50 mg or 75 mg of free base (present as the mesylate salt)

Treatment: Drugs: Trametinib
Each tablet contained 0.5 mg or 2.0 mg of trametinib parent (present as the DMSO solvate)

Treatment: Drugs: Placebos
The placebo capsules and tablets contained the same inactive ingredients and film coatings as the dabrafenib and trametinib study treatment

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Relapse-free Survival (RFS) - Recurrence-free survival was defined as the time from randomization to disease recurrence (local recurrence, distant recurrence, second primary melanoma), or death from any cause.
Timepoint [1] 0 0
Approximately 3.5 years
Secondary outcome [1] 0 0
Overall Survival - Overall survival (OS) of dabrafenib and trametinib as a combination therapy versus placebo
Timepoint [1] 0 0
approximately 3.5 years
Secondary outcome [2] 0 0
Distant Metastasis-free Survival - Distant metastasis-free survival (DMFS) of dabrafenib and trametinib as a combination therapy versus placebo. In the DMFS analysis, the first occurrence of distant metastasis or death (if it occurred before documented recurrence) was counted as an event.
Timepoint [2] 0 0
approximately 3.5 years
Secondary outcome [3] 0 0
Freedom From Relapse - Freedom from relapse (FFR) of dabrafenib and trametinib as a combination therapy versus placebo. In the FFR analysis, local or distant recurrence or a new primary melanoma were counted as events, and patients who died of causes other than melanoma or treatment-related toxicity were censored.
Timepoint [3] 0 0
approximately 3.5 years

Eligibility
Key inclusion criteria
Key

- Completely resected histologically confirmed high-risk [Stage IIIa (LN metastasis more
than 1 mm), IIIb or IIIc cutaneous melanoma determined to be V600E/K mutation positive
by a central laboratory. Patients presenting with initial resectable lymph node
recurrence after a diagnosis of Stage I or II melanoma are eligible.

- Surgically rendered free of disease no more than 12 weeks before randomization.

- Recovered from definitive surgery (e.g. no uncontrolled wound infections or indwelling
drains).

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.

- Adequate hematologic, hepatic, renal and cardiac function.

Key
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Known mucosal or ocular melanoma or the presence of unresectable in-transit
metastases.

- Evidence of distant metastatic disease.

- Prior systemic anti-cancer treatment and radiotherapy for melanoma; prior surgery for
melanoma is allowed.

- History of another malignancy or concurrent malignancy including prior malignant
melanoma. Exceptions to this include: Patients who have been disease-free for 5 years
or patients with a history completely resected non-melanoma skin cancer or
successfully treated in situ carcinoma are eligible, for example cervical cancer in
situ, atypical melanocytic hyperplasia or melanoma in situ, multiple primary
melanomas, or other malignancies for which the patient has been disease free for > 5
years.

- History or current evidence of cardiovascular risk.

- History or current evidence 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
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Novartis Investigative Site - Gateshead
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Novartis Investigative Site - North Sydney
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Novartis Investigative Site - Tweed Heads
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Novartis Investigative Site - Westmead
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Novartis Investigative Site - Greenslopes
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Novartis Investigative Site - Milton
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Novartis Investigative Site - Woolloongabba
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Novartis Investigative Site - Adelaide
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Novartis Investigative Site - Box Hill
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Novartis Investigative Site - Heidelberg
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Novartis Investigative Site - Melbourne
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Novartis Investigative Site - Nedlands
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2290 - Gateshead
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2060 - North Sydney
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2485 - Tweed Heads
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2145 - Westmead
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4120 - Greenslopes
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4064 - Milton
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4102 - Woolloongabba
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5000 - Adelaide
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3128 - Box Hill
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3084 - Heidelberg
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3004 - Melbourne
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6009 - Nedlands
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This was a two-arm, randomized, double-blind Phase III study of dabrafenib in combination
with trametinib versus two placebos in the adjuvant treatment of melanoma after surgical
resection. Patients with completely resected, histologically confirmed, BRAF V600E/K
mutation-positive, high-risk [Stage IIIa (lymph node metastasis >1 mm), IIIb or IIIc]
cutaneous melanoma were screened for eligibility. Subjects were randomized to receive either
dabrafenib (150 milligram (mg) twice daily [BID]) and trametinib (2 mg once daily [QD])
combination therapy or two placebos for 12 months.
Trial website
https://clinicaltrials.gov/show/NCT01682083
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

Summary results
Other publications