A trial with patients who have a tumor that is too big to resect via operation, to treat them with systemic treatment to downsize the tumor, so that after 8 weeks the tumor can be resected and the patient is cured.

Conditions: unresectable stage III/IV melanoma
MedDRA version: 14.1Level: HLTClassification code 10027156Term: Skin melanomas (excl ocular)System Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2013-002616-28-NL

Lead Sponsor: KI-AV

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

1.Patients have provided signed informed consent.
2.Patients have unresectabel stage III melanoma (documented and based on MSD) or stage IV melanoma with = 3 resectable metastases/organ site.
3.Patients have pathologically confirmed BRAF mutation-positive (V600E/K) melanoma as determined via in-house testing with a BRAF mutation assay.
4.Patients are treatment naïve for unresectable melanoma.
5.Patients for whom the intended operation is considered to offer a chance of cure or substantial palliation.
6.Patients have evaluable disease by CT/MRI or PET with = 3 metastases/organ sites.
7.Patients are =18 years of age.
8.Patients are able to swallow and retain oral medication.
9.Women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study.
10.Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to the first dose of study treatment.
11.Patients have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
12.Patients must have adequate organ function as defined in the protocol. Treatment with transfusion, growth factors to meet eligibility criteria will not be allowed.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

1. Patients with known ocular or primary mucosal melanoma.
2. Patients who used any investigational anti-cancer or other drug within 28 days or 5 half-lives, whichever is longer, preceding the first dose of dabrafenib + trametinib.
3. Patients who currently use a prohibited medication or are expected to require any of these medications during treatment with dabrafenib and trametinib.
4. Patients who had any major surgery, radiotherapy, or immunotherapy within the last 4 weeks.
5. Patients with active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs.
6. Patients with a history of glucose-6-phosphate dehydrogenase (G6PD) deficiency.
7. Patients with a history of other malignancy. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible
8. Patients with a history of alcohol or drug abuse within 6 months prior to screening.
9. Patients with psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol, or unwillingness or inability to follow the procedures required in the protocol.
10.Patients with the cardiac abnormalities as defined in the protocol.
11.Pregnant or lactating female.
12.Patients with CNS metastases.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Primary objectives: To assess the ability of dabrafenib + trametinib treatment to downsize melanoma tumor masses to enable R0-resection. <br><br>;Secondary Objective: Secondary objectives: Recurrence free survival; time-to-next treatment, overall survival.;Primary end point(s): The primary endpoint of this study is the % of patients in whom an R0-resection could be performed. This is measured by the pathologist, who handles the resection material (no positive margins) and negative CT-scans. Patients that develop a CR on systemic treatment will of course be included in the analysis. The aim of the study is to enable R0 resection.;Timepoint(s) of evaluation of this end point: 8 weeks after start study treatment.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): As the secondary endpoint recurrence-free survival will be assessed every 3 months by physical exam and CT-scan for 2 years, thereafter every 6 months for 2 year, and once in year 5. Thereafter by physical exam only. This will be assessed only in patients that undergo radical surgery. For patients not undergoing surgery, PFS will be assessed.<br>Time to next treatment is defined as the moment the study treatment starts until start of any following treatment (surgery, RT or systemic treatment) for new lesions. This will be measured in all patients, but patients will be stratified for undergoing surgery or not undergoing surgery. Overall survival will be measured using Kaplan-Meier estimation for the total group of patients as well, again stratified for patients undergoing surgery or no surgery.;Timepoint(s) of evaluation of this end point: During follow-up of the patient.