Patients with advanced melanoma who have received one prior immunotherapy systemic regimen for advanced disease, for whom vemurafenib/cobimetinib treatment has been scheduled by the treating physician. MedDRA version: 21.1 Level: LLT Classification code 10053571 Term: Melanoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: ZELBORAF - 240 MG - COMPRESSA RIVESTITA CON FILM - USO ORALE - BLISTER (ALU/ALU) 56 COMPRESSE
Product Name: Vemurafenib
Product Code: IMP1
Pharmaceutical Form: Film-coated tablet
INN or Pr
Sponsors
FONDAZIONE MELANOMA ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Patients must have histologically confirmed, unresectable stage IIIc or stage IV metastatic melanoma, as defined by the American Joint Committee on Cancer 7th edition. Unresectability of stage IIIc disease must have confirmation from a surgical oncologist 2) Patients with advanced melanoma who have received one prior immunotherapy systemic regimen for advanced disease, for whom vemurafenib/cobimetinib treatment has been scheduled by the treating physician. 3) Adjuvant treatment is allowed, except for anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 agents 4) Patients must be naïve to treatment for locally advanced unresectable or metastatic with BRAF/MEK inhibitors 5) Documentation of BRAFV600 mutation-positive status in melanoma tumor tissue BRAF V600 mutation test 6) At least one measurable lesion according to disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria 7) Eastern Cooperative Oncology Group (ECOG) Performance Status of 0- 2 8) Male or female patient aged = 18 years 9) Able to participate and willing to give written informed consent prior to performance of any study-related procedures and to comply with the study protocol 10) Life expectancy = 12 weeks 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 31 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 31
Exclusion criteria
Exclusion criteria: 1) History of any prior systemic treatment for unresectable stage IIIc or stage IV melanoma (prior anti RAF or MEK agents) other than one prior first-line immunotherapy 2) Palliative radiotherapy within 14 days prior to the first dose of study treatment 3) Major surgery or traumatic injury within 14 days prior to first dose of study treatment 4) Patients with active malignancy (other than BRAF- mutated melanoma) or a previous malignancy within the past 3 years are excluded; except for patients with resected melanoma, resected BCC, resected cutaneous SCC, resected melanoma in-situ, resected carcinoma in-situ of the cervix, and resected carcinoma in-situ of the breast Exclusion Criteria Based on Organ Function Ocular: 5) History of, or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serouschorioretinopathy (CSCR), retinal vein occlusion (RVO) or neovascularmacular degeneration 6) The risk factors for RVO are listed below. Patients will be excluded if they currently have the following conditions: a. Uncontrolled glaucoma with intra-ocular pressures =21 mmHg. b. Serum cholesterol =Grade 2 c. Hypertriglyceridemia = Grade 2 d. Hyperglycemia (fasting) =Grade 2 Cardiac: 7) History of clinically significant cardiac dysfunction, including the following: a. Current unstable angina b. Symptomatic congestive heart failure of New York Heart Association class 2 or higher c. History of congenital long QT syndrome or mean (average of triplicate measurements) QTcF = 450 msec at baseline or uncorrectable abnormalities inserum electrolytes (sodium, potassium, calcium, magnesium, phosphorus) d. Uncontrolled hypertension= Grade 2 (patients with a history hypertension controlled with anti-hypertensives to = Grade 1 are eligible). e. Left ventricular ejection fraction (LVEF) below institutional lower limit of normal (LLN) or below 50%, whichever is lower Central Nervous System: 8) Patients with active/symptomatic CNS lesions are excluded
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy and safety profile of vemurafenib in combination with cobimetinib in advanced melanoma patients treated in the second-line setting after treatment with first-line systemic immunotherapy. The efficacy is measured as 1-year OS rate.;Secondary Objective: ¿ PFS ¿ Objective Response Rate (ORR) ¿ Safety and toxicity of the investigational medicinal products (IMPs) ¿ Health Related Quality of Life (HRQoL) as assessed by the European Organisation for Research and Treatment of Care (EORTC) QLQ-C30;Primary end point(s): OS;Timepoint(s) of evaluation of this end point: The primary endpoint will be 1 year OS, and will be calculated from the first day of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ¿ PFS ¿ Objective Response Rate (ORR);Timepoint(s) of evaluation of this end point: La percentuale di risposta obiettiva ORR e la percentuale di pazienti in vita con o senza progressione della malattia a 6, 12, 18, 24 mesi | — |
Countries
Italy
Contacts
Public ContactStudy Coordinator
Marcello Curvietto
Outcome results
None listed