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
- Conditions
- malignant melanomaMelanoma1002765610040900
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 80
- 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
- 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary endpoint of this study is response rate, defined as the rate of ongoing<br /><br>responses (CR and PR) according to RECIST v1.1 at 12 months after first start<br /><br>of first-line ipilimumab-nivolumab in patients with irresectable stage III or<br /><br>metastatic melanoma.</p><br>
- Secondary Outcome Measures
Name Time Method