Safe Stop Ipilimumab-nivolumab (IPI-NIVO) Trial

Официальное название

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

Обзор

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

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (10)

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

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Нидерланды · 1 центр

• Erasmus MC — Rotterdam

Публикации

• 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

Идентификаторы

NCT: NCT05652673 · NL82177.078.22

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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