None listed
Conditions
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.
Interventions
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
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.
Sponsors
Melanoma Institute Australia
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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
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
Outcome results
None listed