Safe Stop Ipilimumab-nivolumab (IPI-NIVO) Trial
Study Details
Study Description
Brief 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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Early discontinuation of nivolumab
|
Drug: nivolumab
Early discontinuation of nivolumab maintenance therapy in patients with irresectable stage III or metastatic melanoma
|
Outcome Measures
Primary Outcome Measures
- Ongoing response [12 months after start of ipilimumab-nivolumab combination therapy]
The rate of ongoing response at 12 months in patients with irresectable stage III or metastatic melanoma who are treated with first-line ipilimumab-nivolumab and who early discontinue nivolumab upon achieving a CR or PR according to RECIST v1.1
Secondary Outcome Measures
- Ongoing response [24 months after start of treatment]
Ongoing response at 24 months after start of first-line treatment with ipilimumab-nivolumab
- Disease control [5 years after inclusion]
Disease control (CR/PR) at different time points
- duration of response [5 years after inclusion]
Duration of response (CR/PR) measured until progressive/recurrent disease
- Melanoma Specific Survival rate [5 years after inclusion]
Melanoma specific survival measured from start of first-line treatment with ipilimumab-nivolumab until melanoma related death
- Overall Survival [5 years after inclusion]
Overall survival (OS) measured from start of first-line treatment with ipilimumab-nivolumab until death by any cause
- (serious) adverse events [5 years after inclusion]
Impact of discontinuation treatment on (S)AEs
- ORR [5 years after inclusion]
Overall Response Rate (ORR) per RECIST v1.1 in retreated patients
- Re-treatment [5 years after inclusion]
Rate of re-treatment for melanoma
- Disease control (CR/PR/SD [stable disease]/not PD [progressive disease]) after restarting (systemic) treatment for melanoma [5 years after inclusion]
Disease control (CR/PR/SD [stable disease]/not PD [progressive disease]) after restarting (systemic) treatment for melanoma
- Quality of life questionnaires EuroQoL EQ-5D-5 [5 years after inclusion]
Quality of life is measured using questionnaires: EuroQoL EQ-5D-5
Eligibility Criteria
Criteria
Inclusion Criteria:
-
18 years of age or older
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Irresectable stage III or metastatic melanoma
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Treated with at least one dose of first-line ipilimumab-nivolumab and considered to be a candidate for maintenance treatment with nivolumab:
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previous systemic treatment, including immune-checkpoint inhibitors, in (neo)adjuvant setting for resectable melanoma is allowed
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in this protocol, nivolumab maintenance is interchangeable with pembrolizumab maintenance therapy.
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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:
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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
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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
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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.
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Patients should be included after first CR/PR or first confirmed CR/PR according to
RECIST v1.1 30:
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inclusion should take place no later than 5 weeks after first confirmed CR/PR
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in case of SD at first response evaluation, confirmed CR/PR is required for inclusion
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planned and willing to discontinue nivolumab within 4(+1) weeks after inclusion, i.e. first CR/PR or first confirmed CR/PR
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no later than 9 months after start of treatment with ipilimumab-nivolumab
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Presence of MRI brain for the screening of brain metastases (prior to discontinuation of ipilimumab-nivolumab)
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Participants with previously locally treated brain metastases may participate in case they meet the following criteria:
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completely asymptomatic brain metastases at inclusion
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MRI of brain at baseline and for response evaluation during treatment
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Signed and dated informed consent form
Exclusion Criteria:
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Patients with SD/PD according to RECIST v1.1
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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.
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Presence of symptomatic brain metastases:
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prior to first-line treatment with ipilimumab-nivolumab, or;
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when defined as new or progressive brain metastases at the time of study entry;
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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);
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Presence of leptomeningeal metastases;
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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.
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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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Erasmus Medical Center
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NL82177.078.22