Melanoma MedDRA version: 20.0 Level: LLT Classification code 10053571 Term: Melanoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Cotellic 20 mg film-coated tablets
Product Name: Cobimetinib
Product Code: Ro 551-4041/F04-06
Pharmaceutical Form: Film-coated tablet
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General inclusion criteria: - Male or female patient aged >= 18 years - Eastern Coorperative Oncology Group (ECOG) Performance Status of 0-2 - Adequate hematologic and end organ function (renal and liver) - Negative serum pregnancy test prior to commencement of dosing in women of childbearing potential - Absence of any psychological, familial, sociological, or geographical condition that potentially hampers compliance with the study protocol and treatment regimen and follow-up after treatment discontinuation schedule; those conditions should be discussed with the patient before trial entry - Female patients of childbearing potential and male patients with partners of childbearing potential must agree to always use 2 effective forms of contraception during the course of this study and for at least 6 months after completion of study therapy a. Females of childbearing potential are defined as sexually mature women without prior oophorectomy or hysterectomy who have had menses within the last 12 months. b. Females are not considered to be of childbearing potential if amenorrheic for > 12 months but 40 IU/L. c. Effective forms of contraception include surgical sterilization, a reliable barrier, method with spermicide, birth control pills, or contraceptive hormone implants. Please note that potential interactions between vemurafenib and hormonal contraceptives may decrease the effectiveness of hormonal contraceptives. d. d. Male patients who are surgically sterilized are required to use barrier methods of contraception Disease-specific Inclusion Criteria: - Patients with histologically confirmed cutaneous melanoma, either unresectable Stage IIIc or Stage IV metastatic melanoma, as defined by AJCC 7th edition - Documentation of BRAF V600 mutation-positive status in melanoma tumor tissue using a validated tissue test - Patients with measurable or non-measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1) 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 150 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 58
Exclusion criteria
Exclusion criteria: Cancer-Related Exclusion Criteria: 1. History of prior RAF or mitogen-activated protein kinase (MEK) pathway inhibitor treatment 2. Treatment related: a.Palliative radiotherapy within 14 days prior to the first dose of study treatment b. Use of prior chemotherapy or immunotherapy (incl. treatment with an anti-PD1, or anti-PDL1 or anti-CTLA-4 monoclonal antibody) within 4 weeks before first study drug administration Exclusion Criteria Based on Organ Function: - Ocular: Evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/ central serous chorioretinopathy, retinal vein occlusion, or neovascular macular degeneration - Patients will be excluded if they have one of the following conditions: a) Uncontrolled glaucoma with intra-ocular pressures >= 21 mmHg b) Uncontrolled hypercholesterolemia >= Grade 2 c) Hypertriglyceridemia >= Grade 2 d) Hyperglycemia >= Grade 2 - Cardiac: History of clinically significant cardiac dysfunction General exclusion criteria: - Current severe, uncontrolled systemic disease - Major surgery or traumatic injury within 14 days prior to first dose of study treatment - History of malabsorption or other condition that would interfere with absorption of study drugs - the following foods/supplements are prohibited at least 7 days prior to initiation of and during study treatment: a) St. John’s wort or hyperforin (potent CYP3A4 enzyme inducer) b) Grapefruit juice (potent cytochrome P450 CYP3A4 enzyme inhibitor)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To estimate the frequency of the v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation in a new mutation analysis triggered by a mutant plasma cell-free DNA (cfDNA) test result, for patients with BRAF wild-type status based on a prior test result on tissue;Timepoint(s) of evaluation of this end point: Pre-screening period (Day -56 to Day -1); Secondary Objective: To investigate the clinical outcome of all patients, as well as broken down for patients for whom treatment is based on the mutation identified by the prior test result on tissue, and patients for whom treatment is based upon the mutation identified on the new tissue analysis, triggered by the mutant plasma cfDNA test result To investigate the correlation of the initial concentration of the BRAF V600 mutation on cfDNA in plasma with progression-free survival time and duration of response, for all treated patients To estimate the sensitivity and specificity, and the positive and negative predictive value of the results of plasma testing with respect to the prior test result on tissues To characterize the toxicity profile in patients receiving vemurafenib plus cobimetinib ; Primary end point(s): 1. BRAF V600 mutation status determined on plasma cfDNA at onset of the study 2. BRAF V600 mutation status determined on tissue 3. Occurrence of the BRAF V600 mutation on the new mutation analysis for patients with a BRAF wild-type based on a prior tissue test result and a mutation determined on plasma cfDNA | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Objective response rate 2. Progression-free survival 3. Duration of response 4. Overall survival 5. Incidence, nature and severity of adverse events, serious adverse events, and adverse events of special interest, graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events v 4.03 6. Changes in vital signs, electrocardiograms and clinical lab results during the course of the study ;Timepoint(s) of evaluation of this end point: Up to 36 months | — |
Countries
Belgium, Poland
Contacts
Public ContactTrial Information Support Line-TISL
Genentech Inc. c/o F. Hoffmann La Roche Ltd
Outcome results
None listed