Clinical trial · Interventional
Vemurafenib Plus Cobimetinib in Metastatic Melanoma
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
NCT02414750CI-TRIAL-00062405REPOSITterminatedPhase 2ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Why stopped (as posted): Slow accrual and changing treatment landscape
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Metastatic Melanoma | Melanoma | CURATED_BROADER | 0.78 |
Interventions
Interventions (4)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Blood sampling | Procedure | — | UNRESOLVED |
| Positron Emission Tomography | Device | — | UNRESOLVED |
| Tissue sampling | Procedure | — | UNRESOLVED |
| Vemurafenib plus cobimetinib | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Treatment with BRAF/MEK inhibitor
- description
- Treatment with vemurafenib 2dd 960 mg 28/28 plus cobimetinib 1dd 60 mg 21/28. During treatment patient will undergo PET scanning with FLT and FDG, to compare both types of PET scanning. During the study biopsies and blood will be taken from the patients.
- interventionNames
- Drug: Vemurafenib plus cobimetinib
- Device: Positron Emission Tomography
- Procedure: Tissue sampling
- Procedure: Blood sampling
Primary outcomes (4)
- measure
- Progression Free survival (PFS)
- timeFrame
- Participants will be followed until they have progressive disease based on RECIST1.1, an expected median of 10 months.
- measure
- Standardized Uptake Value (SUV) of 18F-FDG and 18F-FLT as measured by PET.
- timeFrame
- Participants will be followed until they have progressive disease based on RECIST1.1, an expected median of 10 months.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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.
References
Publications (2)
- DERIVEDvan der Hiel B, de Wit-van der Veen BJ, van den Eertwegh AJM, Vogel WV, Stokkel MPM, Lopez-Yurda M, Boellaard R, Kapiteijn EW, Hospers GAP, Aarts MJB, de Vos FYFL, Boers-Sonderen MJ, van der Veldt AAM, de Groot JWB, Haanen JBAG. Metabolic parameters on baseline and early [18F]FDG PET/CT as a predictive biomarker for resistance to BRAF/MEK inhibition in advanced cutaneous BRAFV600-mutated melanoma. EJNMMI Res. 2025 May 28;15(1):60. doi: 10.1186/s13550-025-01259-x. PMID 40434500
- DERIVEDvan der Hiel B, Haanen JBAG, Stokkel MPM, Peeper DS, Jimenez CR, Beijnen JH, van de Wiel BA, Boellaard R, van den Eertwegh AJM; REPOSIT study group. Vemurafenib plus cobimetinib in unresectable stage IIIc or stage IV melanoma: response monitoring and resistance prediction with positron emission tomography and tumor characteristics (REPOSIT): study protocol of a phase II, open-label, multicenter study. BMC Cancer. 2017 Sep 15;17(1):649. doi: 10.1186/s12885-017-3626-5. PMID 28915798