NIVOLUMAB for Melanoma|Unresectable stage III melanoma|Metastatic melanoma

Inclusion criteria

• {"criterion_text":"- 18 years of age or older"}
• {"criterion_text":"- lrresectable stage Ill or metastatic melanoma"}
• {"criterion_text":"- 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 ICls, in (neo)adjuvant setting for resectable melanoma is allowed o in this protocol, nivolumab maintenance is interchangeable with pembrolizumab maintenance therapy."}
• {"criterion_text":"- Response evaluation according to RECIST v1 .1 (27) using a diagnostic CT documenting target lesions every 12 (-2/+6) weeks from the start of ipilimumabnivolumab: 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 18 FDG-PET/CT) is allowed if sufficient target lesions are measurable for response evaluation according to RECIST v1 .1 criteria (27) in case of asymptomatic brain metastases prior to start of first-line ipilimumab-nivolumab, intracerebral tumor response should be confirmed using an MRI for response evaluation prior to inclusion in this study."}
• {"criterion_text":"- Patients should be included after first CR/PR or first confirmed CR/PR according to RECIST v1 .1 (27): 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"}
• {"criterion_text":"- Presence of MRI brain for the screening of brain metastases (prior to discontinuation of ipilimumab-nivolumab)"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Signed and dated informed consent form"}

Exclusion criteria

• {"criterion_text":"- Patients with SD/PD according to RECIST v1 .1"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Presence of symptomatic brain metastases: o prior to first-line treatment with ipilimumab-nivolumab, or; o when defined as new or progressive brain metastases at the time of study entry; o 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."}
• {"criterion_text":"- Presence of leptomeningeal metastases;"}
• {"criterion_text":"-\tSystemic chronic steroid therapy (> 1 0mg/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."}
• {"criterion_text":"- 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."}

Primary endpoints

• {"endpoint_text":"- The primary objective of this study is the rate of ongoing response (defined as the absence of disease progression according to RECIST v1 .1 (27) or melanoma­specific mortality) at 12 months after start of treatment in patients with irresectable stage Ill or metastatic melanoma who are treated with first-line ipilimumab­nivolumab and who discontinue nivolumab therapy early (no later than 9 months after treatment commencement with ipilimumab-nivolumab) upon achieving a (confirmed) CR or PR accord","definition_or_measurement_approach":"Ongoing response defined as absence of disease progression according to RECIST v1.1 or melanoma-specific mortality, assessed at 12 months after start of treatment."}

Secondary endpoints

• {"endpoint_text":"- A.\tPatient outcomes: 1.\tOngoing response at 24 months after treatment commencement with ipilimumab-nivolumab 2.\tResponse (CR/PR) at different time points (see Table 1 and Figure 1 for follow-up interval) 3.\tDuration of response (CR/PR) measured until progressive/recurrent disease 4.\tMelanoma specific survival measured from start of first-line treatment with ipilimumab-nivolumab until melanoma related death 5.\tOS measured from start of combination treatment with ipilimumab-nivolumab until death","definition_or_measurement_approach":"Ongoing response at 24 months (RECIST v1.1-based assessment), response rates (CR/PR) at specified time points, duration of response measured until progression/recurrence, melanoma-specific survival measured from start of first-line treatment until melanoma-related death, and overall survival measured from start of combination treatment until death."}
• {"endpoint_text":"- B.\tCost-effectiveness analysis 1.\tImpact on productivity with respect to paid and unpaid work 2.\tImpact on healthcare resource 3.\tImpact of early discontinuation of PD-1 blockade on hours of informal care","definition_or_measurement_approach":"Health-economic endpoints assessing productivity (paid/unpaid work), healthcare resource use, and hours of informal care; methods not further specified in the record provided."}
• {"endpoint_text":"- C. Quality of life assessment in patients with irresectable stage Ill 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.","definition_or_measurement_approach":"Quality of life assessed by questionnaires at inclusion and scheduled intervals (every 12 weeks in year 1, every 4 months in year 2, every 6 months in year 3, and one set in year 5). Specific QoL instruments not specified in the provided record."}

Netherlands

Earliest CTIS Part Ii Submission Date

06-09-2024

Latest Decision Or Authorization Date

11-09-2024

Processing Time Days

5

Number Of Sites

13

Number Of Participants

80

Primary sponsor

Full Name

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands