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Trial registered on ANZCTR


Trial ID
ACTRN12613000737730
Ethics application status
Approved
Date submitted
13/05/2013
Date registered
3/07/2013
Date last updated
28/09/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
An open label, single centre, phase II pilot study of neoadjuvant dabrafenib + trametinib in patients with resectable AJCC Stage IIIB-C BRAF V600 mutation positive melanoma
Scientific title
An open label, single centre, phase II pilot study to determine the pathological response rate to 12 weeks of neoadjuvant dabrafenib + trametinib in patients with resectable AJCC Stage IIIB-C BRAF V600 mutation positive melanoma
Secondary ID [1] 282497 0
Protocol Number 200332
Universal Trial Number (UTN)
U1111-1143-0183
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 289143 0
Condition category
Condition code
Cancer 289476 289476 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Dabrafenib tablet 150 mg orally twice daily and trametinib tablet 2 mg orally once daily as neoadjuvant treatment for 3 months followed immediately by complete lymph node dissection surgery. Three days following surgery, patients will recommence dabrafenib 150 mg twice daily and trametinib 2 mg once daily for a further 9 months. Compliance will be monitored by asking patients to keep a dosing diary and at the end of each cycle, the patient will return to clinic with the diary and drug containers and study coordinators will check compliance.
Intervention code [1] 287150 0
Treatment: Drugs
Intervention code [2] 287288 0
Treatment: Surgery
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 289579 0
The percentage of patients with a partial pathological response (a reduction in the proportion of viable melanoma tissue) or complete pathological response (no viable melanoma tissue) at 12 weeks post neoadjuvant treatment. The pathological response is assessed by the % of viable melanoma cells after 12 weeks of neoadjuvant treatment.
Timepoint [1] 289579 0
12 weeks after commencement of neoadjuvant study treatment
Secondary outcome [1] 302770 0
The effects of neoadjuvant study treatment on surgical outcomes: episodes of infection requiring antibiotics, time from surgery to removal of drain, episodes of seroma formation requiring drainage and episodes of bleeding requiring return to theatre and/or transfusion.
Timepoint [1] 302770 0
12 weeks after commencement of neoadjuvant study treatment.

Eligibility
Key inclusion criteria
>18 years of age
Written informed consent
Histologically confirmed AJCC Stage IIIB or IIIC cutaneous melanoma or unknown primary and V600 mutation positive with sufficient nodal disease to enable 4 biopsies (core, excisional or incisional).
Able to swallow and retain oral medication
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
Adequate organ function
Women of childbearing potential: negative serum pregnancy test and effective contraception from 14 days prior to study treatment until 4 months after the last dose
Men with female partner of childbearing potential to use effective contraception from 14 days prior to study treatment until 4 months after the last dose
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Mucosal or ocular melanoma or any in-transit metastases
Distant metastatic disease on screening
Prior systemic anti-cancer treatment (except surgery)
Any investigational drug within 28 days or 5 half-lives
Current or expected use of a prohibited medication
Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments
Human Immunodeficiency Virus (HIV)
Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Another malignancy or concurrent malignancy unless disease-free for 3 years and with a life expectancy of > 5 years
Cardiovascular risk including: QTc =480 msec, uncontrolled arrhythmias, acute coronary syndromes, coronary angioplasty or stenting within 6 months, NYHA = Grade 2 heart failure, intra-cardiac defibrillator or permanent pacemaker, abnormal cardiac valve morphology (= Grade 2), treatment refractory hypertension systolic> 140 mm Hg and/or diastolic > 90 mm Hg
Evidence/risk of retinal vein occlusion or central serous retinopathy
Serious or unstable pre-existing medical conditions or other conditions that could interfere with the subject’s safety, consent, or compliance
Pregnant or breastfeeding females

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The overall response rate will be calculated as the number of patients with a complete or partial RECIST 1.1 response divided by the total number of patients. Pathological response will be calculated as the proportion of patients with either a complete pathological response (no viable melanoma tissue) or a reduction in the proportion of viable melanoma tissue at lymph node dissection compared with baseline. Complete and partial pathological responses will also be reported separately. Exact confidence limits calculated with the Clopper-Pearson method will be reported together with the overall response and pathological response rates.

Sample size is based on a complete pathological response rate of <10% for unsuccessful treatment or >30% for successful treatment.

Recruitment
Recruitment status
Active, not recruiting
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
Recruitment hospital [1] 6618 0
The Poche Centre, Melanoma Institute Australia - North Sydney

Funding & Sponsors
Funding source category [1] 287280 0
Commercial sector/Industry
Name [1] 287280 0
GlaxoSmithKline Australia
Address [1] 287280 0
Level 4, 436 Johnston Street Abbotsford Victoria 3067
Country [1] 287280 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Melanoma Institute Australia
Address
40 Rocklands Rd, Wollstonecraft NSW 2065
Country
Australia
Secondary sponsor category [1] 286032 0
None
Name [1] 286032 0
Address [1] 286032 0
Country [1] 286032 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289527 0
Ethics committee address [1] 289527 0
Translational Research Centre, 97-105 Boundary Street, Darlinghurst NSW 2010
Ethics committee country [1] 289527 0
Australia
Date submitted for ethics approval [1] 289527 0
02/07/2013
Approval date [1] 289527 0
28/08/2013
Ethics approval number [1] 289527 0

Summary
Brief summary
This study is evaluating the effect of the drugs dabrafenib and trametinib given prior to surgery and after for the treatment of melanoma.
Who is it for? You may be eligible to join this study if you are aged 18 years or above and have been diagnosed with AJCC (American Joint Committee on Cancer) Stage IIIB or IIIC BRAF V600 mutation positive melanoma.
Trial details: All participants in this study will take dabrafenib 150 mg tablets twice daily and trametinib 2 mg tablets once daily for 3 months. They will then undergo complete lymph node dissection surgery, followed by treatment with twice daily dabrafenib 150 mg and once daily trametinib 2 mg for a further 9 months. Participants will be assessed at 12 weeks post treatment in order to evaluate treatment response and surgical outcomes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 40010 0
Prof Georgina Long
Address 40010 0
Melanoma Institute Australia
40 Rocklands Road, Wollstonecraft NSW 2065
Country 40010 0
Australia
Phone 40010 0
+61 2 9911 7363
Fax 40010 0
Email 40010 0
Georgina.Long@melanoma.org.au
Contact person for public queries
Name 40011 0
Ms Maria Gonzalez
Address 40011 0
Melanoma Institute Australia
40 Rocklands Road, Wollstonecraft NSW 2065
Country 40011 0
Australia
Phone 40011 0
+61 2 9911 7200
Fax 40011 0
Email 40011 0
Maria.Gonzalez@melanoma.org.au
Contact person for scientific queries
Name 40012 0
Ms Maria Gonzalez
Address 40012 0
Melanoma Institute Australia
40 Rocklands Road, Wollstonecraft NSW 2065
Country 40012 0
Australia
Phone 40012 0
+61 2 9911 7200
Fax 40012 0
Email 40012 0
Maria Gonzalez@melanoma.org.au