malignant melanoma Melanoma
Conditions
Interventions
Discontinuation of (maintenance) treatment with nivolumab at achieving CR
Sponsors
Erasmus MC, Universitair Medisch Centrum Rotterdam
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - 18 years of age or older - irresectable stage III or metastatic melanoma - Treated with at least one dose of first-line ipilimumab-nivolumab and considered to be a candidate for maintenance treatment with nivolumab. o Previous systemic treatment, including ICIs, in (neo)adjuvant setting for resectable melanoma is allowed o In this protocol, nivolumab maintenance is interchangeable with pembrolizumab maintenance therapy. - Response evaluation according to RECIST v1.1 using a diagnostic CT documenting target lesions every 12 (-2/+6) weeks from the start of ipilimumab-nivolumab; o 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 o 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. o In case of asymptomatic brain metastases prior to start of first-line ipilimumab-nivolumab, intracerebral tumor response should be confirmed using an MRI prior to inclusion - Patients should be included after first CR/PR or first confirmed CR/PR according to RECIST v1.1 o Inclusion should take place no later than 5 weeks after first confirmed CR/PR o In case of SD at first response evaluation, confirmed CR/PR is required for inclusion o eligible and willing to discontinue nivolumab within 4(+1) weeks after inclusion, i.e. first CR/PR or first confirmed CR/PR o no later than 9 months after start of treatment with ipilimumab-nivolumab - Presence of MRI brain for the screening of brain metastases (prior to discontinuation of ipilimumab-nivolumab) - Participants with previously locally treated brain metastases may participate in case they meet the following criteria: o completely asymptomatic brain metastases at inclusion o MRI of brain at baseline and for response evaluation during treatment - Signed and dated informed consent form
Exclusion criteria
Exclusion criteria: - Patients with SD/PD according to RECIST v1.1 - Malignant disease other than being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to start of study treatment; completely resected basal cell and squamous cell skin cancers and any completely resected carcinoma in situ. - Presence of symptomatic brain metastases * prior to first-line treatment with ipilimumab-nivolumab, or; * when defined as new or progressive brain metastases at the time of study entry; * brain metastases with need for steroid treatment in the last 8 weeks prior to study entry Note: An incidental epileptic seizure caused by a brain lesion is not considered an exclusion criterion. (provided that the other in- and exclusion criteria are met); - Presence of leptomeningeal metastases; - Systemic chronic steroid therapy (>10mg/day prednisone or equivalent) at inclusion or patients who need or needed any other second-line immunosuppressive therapy (e.g. infliximab, mycophenolate mofetil) for the treatment of irAEs. Note: local steroids such as topical, inhaled, nasal and ophthalmic steroids are allowed. - Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial. This comprises each and every condition or circumstance preventing the patient from showing up to the outpatient controls and/or undergoing the CT-scans, or preventing the patient from (adequately) filling out the questionnaires
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoint of this study is response rate, defined as the rate of ongoing responses (CR and PR) according to RECIST v1.1 at 12 months after first start of first-line ipilimumab-nivolumab in patients with irresectable stage III or metastatic melanoma. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary objectives of this study include the evaluation of: A. Patient outcomes: 1. Ongoing response at 24 months after start of first-line treatment with ipilimumab-nivolumab 2. Response (CR/PR) at different time points 3. Duration of response (CR/PR) measured until progressive/recurrent disease 4. Melanoma specific survival measured from start of first-line treatment with ipilimumab-nivolumab until melanoma related death 5. Overall survival (OS) measured from start of first-line treatment with ipilimumab-nivolumab until death by any cause 6. Impact of discontinuation treatment on (S)AEs 7. Overall Response Rate (ORR) per RECIST v1.1 in retreated patients 8. Need and feasibility of restarting (systemic) treatment for melanoma 9. Disease control (CR/PR/SD/not PD) after restarting (systemic) anti-melanoma treatment B. Cost-effectiveness analysis 1. Impact on productivity with respect to paid and unpaid work 2. Impact on healthcare resource 3. Impact of early discontinuation of treatment on hours of informal care C. Quality of life assessment in patients with irresectable stage III or metastatic melanoma who did not start nivolumab maintenance therapy or discontinued nivolumab maintenance therapy early. Patients will fill out the QoL questionnaires at inclusion, every 12 weeks in the first year of follow up, every 4 months in year 2, every 6 months in year 3 and one set of questionnaires in year 5. | — |
Countries
Netherlands
Outcome results
None listed