melanoma skin cancer
Conditions
Interventions
None listed
Sponsors
Werkgroep Immunotherapie Nederland voor Oncologie (WIN-O)
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Patients with histologically confirmed melanoma, either unresectable stage IIIc or stage IV metastatic melanoma, as defined by AJCC 7th edition. • Prior BRAF/MEK inhibition is allowed only when given for a period of at most 12 weeks prior to immunotherapy AND no progression is seen on ceCT at the time of discontinuation of BRAF/MEK inhibitor. Prior immunotherapy (including ipilimumab) is allowed. • Documentation of BRAFV600E or BRAFV600K mutation-positive status in melanoma tumor tissue (archival or newly obtained tumor samples). • Measurable disease per RECIST v1.1, which are accessible to biopsies. • Biopsy lesion is within scan reach of diagnostic CT and PET-CT (thorax- abdomen-pelvis) • ECOG performance status of 0 or 1. • Male or female patient aged >= 18 years. • Life expectancy >= 12 weeks. • Adequate hematologic and end organ function within 14 days prior to first dose of study drug treatment.
Exclusion criteria
Exclusion criteria: • History of prior RAF or MEK pathway inhibitor treatment longer than 21 weeks or shorter than 12 weeks but with clinical or radiological signs of progression. • Palliative radiotherapy, major surgery or traumatic injury within 14 days prior to the first dose of study treatment. • Active malignancy within the past 3 years other than melanoma that could potentially interfere with the interpretation of efficacy measures, except for patients with resected BCC or SCC of the skin, melanoma in-situ, carcinoma in-situ of the cervix, and carcinoma in-situ of the breast. • History of or evidence of retinal pathology, clinically significant cardiac dysfunction, patients with symptomatic CNS lesions, renal or liver dysfunction as described in main protocol (REPOSIT NL48639.031.14). • Pregnant, lactating, or breast-feeding. • Unwillingness or inability to comply with study and follow-up procedures (i.e. severe anxiety disorder preventing PET/CT imaging.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • Progression Free survival (PFS) • Correlation between changes of metabolic tracer uptake on PET and of size on diagnostic CT according to RECIST 1.1 from baseline, Day 14/15 Cycle 1, Day 21 Cycle 2 and at the time of progression. • Diagnostic accuracy and best cut-off values of PET at Day 14/15 Cycle 1 and Day 21 Cycle 2 for distinguishing responders from non-responders. • Investigation of the continuous parameters of PET in association with Progression Free Survival. | — |
Secondary
| Measure | Time frame |
|---|---|
| • Correlation of PET-imaging with 18F-FDG PET and 18F-FLT PET between baseline and Day 14/15 Cycle 1 by means of Standardized Uptake Value. • Correlation of PET-imaging with 18F-FDG PET and 18F-FLT PET at the time of progression by means of Standard Uptake Value. • Correlation between 18F-FDG/FLT uptake and immunohistochemical analysis in responders and non responders early after the initiation of therapy. • Correlation between 18F-FDG/FLT uptake and resistance by means of diagnostic CT and PFS. • Best quantification of metabolic imaging. Various quantitative measures of radiotracer uptake determined in RECIST 1.1 target lesions, correlated to PFS and OS. • Correlation between genetic analysis and resistance in terms of RECIST1.1 criteria on diagnostic CT and PFS. • Correlation between phosphoprotein profiles and resistance in terms of RECIST1.1 criteria on diagnostic CT and PFS. • Overall Survival (OS) • Drug level monitoring of vemurafenib and cobimetinib (GDC-0973) at Day 15 Cycle 1 compared to tumor response (RECIST1.1 criteria) and PFS. • Drug level monitoring of vemurafenib and cobimetinib (GDC-0973) at Day 15 Cycle 1 compared to 18F-FDG/FLT uptake. • ECOG Performance status | — |
Countries
Netherlands
Outcome results
None listed