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
- Conditions
- MelanomaCancer - Malignant melanoma
- Registration Number
- ACTRN12613000737730
- Lead Sponsor
- Melanoma Institute Australia
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- All
- Target Recruitment
- 35
>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
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
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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.[12 weeks after commencement of neoadjuvant study treatment]
- Secondary Outcome Measures
Name Time Method 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.[12 weeks after commencement of neoadjuvant study treatment.]