A Phase II, Open-Label, Multicenter Study of Vemurafenib plus Cobimetinib (GDC-0973) in Unresectable Stage IIIc or Stage IV Melanoma; Response Monitoring and Resistance Prediction with Positron Emission Tomography and Tumor Characteristics.
- Conditions
- melanomaskin cancer10040900
- Registration Number
- NL-OMON44689
- Lead Sponsor
- Werkgroep Immunotherapie Nederland voor Oncologie (WIN-O)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 90
• 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.
• 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.
Study & Design
- Study Type
- Observational invasive
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>• Progression Free survival (PFS)<br /><br>• Correlation between changes of metabolic tracer uptake on PET and of size on<br /><br>diagnostic CT according to RECIST 1.1 from baseline, Day 14/15 Cycle 1, Day 21<br /><br>Cycle 2 and at the time of progression.<br /><br>• Diagnostic accuracy and best cut-off values of PET at Day 14/15 Cycle 1 and<br /><br>Day 21 Cycle 2 for distinguishing responders from non-responders.<br /><br>• Investigation of the continuous parameters of PET in association with<br /><br>Progression Free Survival.</p><br>
- Secondary Outcome Measures
Name Time Method