Safe Stop Ipilimumab-nivolumab (IPI-NIVO) Trial

Launched by ERASMUS MEDICAL CENTER · Dec 14, 2022

Keywords

ClinConnect Summary

The Safe Stop Ipilimumab-Nivolumab (IPI-NIVO) Trial is investigating whether patients with advanced melanoma, specifically stage III or IV, can safely stop taking the drug nivolumab after showing a positive response to their treatment. This trial is for adults aged 18 and older who have not had surgery for their melanoma but have started treatment with both ipilimumab and nivolumab and have seen either a complete or partial response to the therapy. Participants will need to have specific imaging tests to confirm their response and must be willing to stop nivolumab treatment within a few weeks after their response is confirmed.

If you join this trial, you'll be monitored closely through regular scans to track your progress, and you’ll work with your healthcare team to ensure that stopping nivolumab is safe for you. It’s important to note that there are certain criteria you must meet to participate, such as having no active brain metastases and being able to attend follow-up appointments. This study may help improve treatment approaches for melanoma patients in the future.

Gender

ALL

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