Safe Stop Ipilimumab-nivolumab (IPI-NIVO) Trial

Official title

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

Overview

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

Interventions

• Drug nivolumab
  Early discontinuation of nivolumab maintenance therapy in patients with irresectable stage III or metastatic melanoma

Primary outcome measures

• Ongoing response [Time frame: 12 months after start of ipilimumab-nivolumab combination therapy]

Secondary outcome measures (10)

• Ongoing response [Time frame: 24 months after start of treatment]
• Disease control [Time frame: 5 years after inclusion]
• duration of response [Time frame: 5 years after inclusion]
• Melanoma Specific Survival rate [Time frame: 5 years after inclusion]
• Overall Survival [Time frame: 5 years after inclusion]
• (serious) adverse events [Time frame: 5 years after inclusion]
• ORR [Time frame: 5 years after inclusion]
• Re-treatment [Time frame: 5 years after inclusion]
• Disease control (CR/PR/SD [stable disease]/not PD [progressive disease]) after restarting (systemic) treatment for melanoma [Time frame: 5 years after inclusion]
• Quality of life questionnaires EuroQoL EQ-5D-5 [Time frame: 5 years after inclusion]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Netherlands · 1 center

• Erasmus MC — Rotterdam

Publications

• Janssen JC, van Dijk B, de Joode K, Aarts MJB, van den Berkmortel FWPJ, Blank CU, Boers-Sonderen MJ, van den Eertwegh AJM, de Groot JWB, Jalving M, de Jonge MJA, Joosse A, Kapiteijn E, Kamphuis-Huismans AM, Naipal KAT, Piersma D, Rikhof B, Westgeest HM, Vreugdenhil G, Oomen-de Hoop E, Mulder EEAP, van der Veldt AAM. Safe Stop IPI-NIVO trial: early discontinuation of nivolumab upon achieving a comp PMID 38783238

Identifiers

NCT: NCT05652673 · NL82177.078.22

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗