malignant melanoma Melanoma
Conditions
Interventions
Discontinuation of PD-1 blockade (nivolumab or pembrolizumab) at achieving CR
or PR.
Sponsors
Erasmus MC, Universitair Medisch Centrum Rotterdam
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - advanced or metastatic melanoma - current treatment with first-line nivolumab or pembrolizumab for advanced or metastatic melanoma; previous systemic treatment, including immunotherapy, in (neo)adjuvant setting for resectable melanoma is allowed - documented diagnostic CT at start of PD-1 blockade with nivolumab or pembrolizumab • For patients with CR on a diagnostic CT at response evaluation, a low dose-CT (which is usually part of 18FDG-PET/CT) is allowed at baseline • For patients with PR on a diagnostic CT at response evaluation, a low dose-CT (which is usually part of 18FDG-PET/CT) is allowed if sufficient target lesions are measurable for response evaluation according to RECIST v1.1 criteria. In this specific case the sponsor should be consulted. - documented tumor response evaluation every 12 (±1) weeks according to RECIST v1.1 (34) using a diagnostic CT as per standard practice - presence of MRI brain for the screening of brain metastases (prior to discontinuation of PD-1 blockade) - willingness to discontinue nivolumab or pembrolizumab within 6 (+1) weeks weeks after confirmation of CR or PR before the full period of 2 years therapy
Exclusion criteria
Exclusion criteria: Concomitant systemic therapies with other anti-cancer agents, e.g. BRAF-inhibitor, anti-CTLA4 (e.g. ipilimumab), or other PD-1 blockade than nivolumab or pembrolizumab
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is the rate of ongoing responses (CR and PR) according to RECIST v1.1 at 24 months after first start of nivolumab or pembrolizumab. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary endpoints include: 1a. Total duration of response after first documented CR or PR followed by treatment interruption 1b. Duration of response (CR and PR) after discontinuation of nivolumab or pembrolizumab 2. Progression-free survival (PFS) from start of nivolumab/pembrolizumab until first PD (PFS1) 3a. Rate of reintroduction of nivolumab/pembrolizumab upon first PD 3b. Rate of introduction of other systemic therapy (i.e. other than nivolumab/pembrolizumab) upon first PD 4a. Best response on rechallenge with nivolumab/pembrolizumab 4b. Best tumor response after introduction of other systemic therapy (i.e. other than monotherapy PD-1 blockade) 5a. PFS after reintroduction of nivolumab/pembrolizumab (PFS2a) 5b. PFS after introduction other systemic therapy (i.e. other than monotherapy PD-1 blockade) (PFS2b) 6. Total PFS (PFSTotal) defined as the period from initial start of PD-1 blockade until final PD (including period after discontinuation and (re)introduction of nivolumab/pembrolizumab or other salvage therapy) 6b. Overall survival (OS) 7. Rate of grade 3-4 adverse events (AEs) after discontinuation or reintroduction of nivolumab/pembrolizumab 8. Change in tumor burden since the start and after early discontinuation of PD-1 blockade 9. Change in QoL after discontinuation of PD-1 blockade 10. Change in fear of disease recurrence/progression 11. Change in productivity (paid and unpaid work) after discontinuation of PD-1 blockade 12. Change in healthcare resource (within and outside the hospital) after discontinuation of PD-1 blockade 13. Change in hours of informal care after discontinuation of PD-1 blockade 14. QoL at disease progression and restart of systemic therapy (when applicable) 15. Change in QoL after discontinuation of radiological follow-up | — |
Countries
Netherlands
Outcome results
None listed