safe stop ipilimumab-nivolumab (ipi-nivo) trial

Conditions: Melanoma Stage IV; Melanoma Stage III; Immunotherapy; Toxicity, Drug

Summary: safe stop ipi-nivo trial: early discontinuation of nivolumab upon achieving a (confirmed) complete or partial response in patients with irresectable stage iii or metastatic melanoma treated with first-line ipilimumab-nivolumab


Eligibility 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: * previous systemic treatment, including immune-checkpoint inhibitors, in (neo)adjuvant setting for resectable melanoma is allowed * in this protocol, nivolumab maintenance is interchangeable with pembrolizumab maintenance therapy. * response evaluation according to recist v1.1 30 using a diagnostic ct documenting target lesions every 12 (-2/+6) weeks from the start of ipilimumab-nivolumab: * 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 30 * 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. * patients should be included after first cr/pr or first confirmed cr/pr according to recist v1.1 30: * inclusion should take place no later than 5 weeks after first confirmed cr/pr * in case of sd at first response evaluation, confirmed cr/pr is required for inclusion * planned and willing to discontinue nivolumab within 4(+1) weeks after inclusion, i.e. first cr/pr or first confirmed cr/pr * 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: * completely asymptomatic brain metastases at inclusion * mri of brain at baseline and for response evaluation during treatment * signed and dated informed consent form 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 immune related adverse events (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