Vemurafenib Plus Cobimetinib in Metastatic Melanoma

• Status: Unknown status
• Trial end date: 2018-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a single arm explorative phase II clinical trial in 90 subjects with advanced stage melanoma harbouring a BRAFV600 mutation. PET imaging and molecular diagnostics are combined in order to monitor response to treatment with vemurafenib plus cobimetinib, examine development of resistance and correlate changes in metabolic/proliferative activity with extend of target inhibition.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Netherlands Working Group on Immunotherapy of Oncology
• Collaborators: Hoffmann-La Roche; The Netherlands Cancer Institute; VU University Medical Center
• Treatments: Vemurafenib

Criteria

Inclusion Criteria:

• Patients with histologically confirmed melanoma, either unresectable stage IIIc or stage IV metastatic melanoma, as defined by AJCC 7th edition.

• Patients must be naïve to treatment for locally advanced unresectable or metastatic disease. 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:

• History of prior RAF or MEK pathway inhibitor treatment.

• 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 active 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.