Melanoma
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of two different schedules of administration of vemurafenib in combination with cobimetinib (continuous and intermittent) in previously untreated BRAFV600- mutation positive patients with unresectable locally advanced or metastatic melanoma.
Interventions
Comparison between different treatment regimens
Sponsors
Roche Farma, S.A
Pivotal S.L.
Grupo Español Multidisciplinar de Melanoma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Disease-Specific Inclusion Criteria: 1. Patients with histologically confirmed melanoma, either unresectable stage IIIc or stage IV metastatic melanoma. 2. Patients must be naïve to treatment for locally advanced unresectable or metastatic disease. 3. Documentation of BRAFV600 mutation-positive status in melanoma tumor tissue. 4. Measurable disease per RECIST v1.1. 5. ECOG performance status of 0 or 1. 6. Additionally, patients to be included in the biomarker sub- study should meet the following criteria: * Consent to provide archival tissue for biomarker analyses. * Consent to undergo tumor biopsies. General Inclusion Criteria: 7. Male or female patient aged major or equal 18 years. 8. Able to participate and willing to give written informed. 9. Life expectancy mayor o igual 12 weeks. 10. Adequate hematologic and end organ function, within 14 days prior to first dose of study drug treatment: * ANC major or equal 1.5 × 109/L. * Platelet count major or equal 100 × 109/L. * Hemoglobin major or equal 9 g/dL. * Albumin major or equal 2.5 g/dL. * Bilirubin minor or equal 1.5 × the upper limit of normal (ULN). * AST, ALT, and alkaline phosphatase minor or equal 3 × ULN, with the following exceptions: * Patients with documented liver metastases: AST and/or ALT minor or equal 5 × ULN. * Patients with documented liver or bone metastases alkaline phosphatase minor o equal 5 × ULN. * Serum creatinine minor o equal 1.5 × ULN or CrCl major or equal 40 mL/min on the basis of measured CrCl from a 24- hour urine collection. 11. 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. 12. Negative serum pregnancy test within 10 days prior to commencement of dosing in women of childbearing potential. 13. Absence of any psychological, familial, sociological, or geographical condition that potentially hampers compliance with the study protocol and follow-up after treatment discontinuation schedule.
Exclusion criteria
Cancer-Related
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression Free Survival (PFS) | Through study completion, up to 42 months |
Secondary
| Measure | Time frame |
|---|---|
| Overall Response Rate (ORR) | Through study completion, up to 42 months |
| Progression Free Survival (PFS) at one and two years | At one and two years |
| Overall Survival (OS) at one and two years | At one and two years |
| Adverse Events (AE) occurrence | Through study completion, up to 42 months |
| Adverse Events of Special Interest (AESI) occurrence | Through study completion, up to 42 months |
| Serious Adverse Events (SAE) occurrence | Through study completion, up to 42 months |
Other
| Measure | Time frame | Description |
|---|---|---|
| Analysis of disease's resistance mechanisms (Translational sub-study) | Through study completion, up to 42 months | Determination of resistance mechanisms in secuential biopsies of the disease. |
| BRAF mutation determination (Translational sub-study) | Through study completion, up to 42 months | Analysis of prognostic and predictive value of BRAF mutation in cell-free DNA (cfDNA) samples, and its role in disease evolution monitoring. |
| Analysis of resistance mechanisms to the combination of vemurafenib and cobimetinib (Translational sub-study) | Through study completion, up to 42 months | Non-invasive monitorization of resistance mechanisms, through selected gene expression cuantification from blood mRNA. |
Countries
Spain
Outcome results
None listed