Metastatic melanoma MedDRA version: 16.1 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Zelboraf
Product Name: Zelboraf
Pharmaceutical Form: Coated tablet
INN or Proposed INN: vemurafenib
CAS Number: 918504-65-1
Other descriptive name: VEMURAFENIB
Concentration unit: mg milli
Sponsors
Department of Oncology, Aarhus University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Histologically verified unresectable stage III or stage IV melanoma with documented BRAF V600 mutation determined by the cobas® 4800 BRAF mutation test •Age between 18 and 70 •ECOG performance status (PS) 0-2 •Patients must have measurable target lesions disease as defined by RECIST v1.1 •Prior medical treatment for metastatic melanoma is allowed, except previous treatment with BRAF-inhibitor and IL-2 based immunotherapy •Adequate cardiac function (less or equal to NYHA II). In the case of previous myocardial infarction echocardiography or MUGA-scan must be performed and left ventricle ejection fraction must be found normal •Adequate hematologic, renal and liver function as defined by laboratory values performed within 2 weeks of enrolment: o Absolute neutrophil count (ANC) = 1.5 x 109/L o Platelet count = 100 x 109/L o Serum creatinine = 1.5 times upper limit of normal (ULN) or - creatinine clearance (CrCl) > 50 mL/hr by Cockroft–Gault formula o Alanine aminotransferase (ALAT) = 2.5 times ULN (= 5 times ULN if considered due to liver metastasis) o Serum bilirubin = 1.5 times ULN o Alkaline phosphatase = 2.5 times ULN (= 5 times ULN if considered due to liver metastasis) •Patients must have absence of any underlying medical or psychiatric condition, which in the opinion of the investigator, will make the administration of the study drugs hazardous or obscure the interpretation of adverse events •Fertile men and women must be using an effective method of contraception during treatment and for at least one month after completion of treatment •Women of child-bearing potential (WOCBP) must have a negative pregnancy test (HCG-urinalysis) before trial entry •Signed informed consent must be obtained prior to performing any study-related procedures. Testing for the V600 BRAF-mutation is considered as a standard procedure 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 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: •Any known severe and symptomatic autoimmune diseases that upon the opinion of the Investigators may conflict with the administration of the study medication. •Cerebral metastases. Patients that have been radically treated (neurosurgery or stereotactic radiotherapy) for a solitary cerebral metastasis may be included if MRI of the brain performed at least one month after treatment is without evidence of disease activity •Patients must not be dependent on systemic treatment with corticosteroids or other immunosuppressing agents •Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that may compromise adequate absorption. Patients must be able to swallow tablets •Uncontrolled infectious disease (requiring treatment with intravenous antibiotics) •Second malignancy in the past 5 years with the exception of surgically cured carcinoma in situ of the cervix or basal and squamous cell carcinoma of the skin. •QTc-interval > 500 ms •Any psychological, familial, sociological or geographical condition that upon the opinion of the investigators may affect the compliance with the protocol and follow-up schedule
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate 6 month progression free-survival (PFS) rate of vemurafenib in combination with interleukin-2 (IL-2) and pegylated interferon (IFN) in patients with BRAF-mutated metastatic melanoma;Secondary Objective: •To evaluate the safety and tolerability of vemurafenib in combination with IL-2/IFN •To evaluate 1-year survival rate (OS) •To evaluate overall response rates as defined by RECIST v.1.1 •To evaluate the number of long-term survivors by estimating the 5-year survival rate •To evaluate predictive and prognostic biomarkers for response and survival ;Primary end point(s): Progression free survival (PFS) ;Timepoint(s) of evaluation of this end point: 6 months after the inclusion of the last patient | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Grade and number of adverse events 2. Overall survival after 1 year 3. Overall survival after 5 years 4.Evaluation of possible prognostic and predictive biomarkers;Timepoint(s) of evaluation of this end point: The primary analysis of efficacy and safety parameters will be performed when all 50 patients enrolled in the study have either died, withdrawn consent or have been followed for at least 6 months. The final analysis of this study will be performed when all patients enrolled have either died, withdrawn consent, are lost to follow up or have been followed up for up to 5 years. | — |
Countries
Denmark
Contacts
Public ContactHenrik Schmidt
Department of Oncology, Aarhus University Hospital
Outcome results
None listed