Clinical trial NCT05652673: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Melanoma Stage IV
Melanoma Stage III
Immunotherapy
Toxicity, Drug
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
First posted: 2022-12-15
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Ongoing response
timeFrame: 12 months after start of ipilimumab-nivolumab combination therapy
Secondary outcomes:
measure: Ongoing response
timeFrame: 24 months after start of treatment
measure: Disease control
timeFrame: 5 years after inclusion
measure: duration of response
timeFrame: 5 years after inclusion
measure: Melanoma Specific Survival rate
timeFrame: 5 years after inclusion
measure: Overall Survival
timeFrame: 5 years after inclusion
measure: (serious) adverse events
timeFrame: 5 years after inclusion
measure: ORR
timeFrame: 5 years after inclusion
measure: Re-treatment
timeFrame: 5 years after inclusion
measure: Disease control (CR/PR/SD [stable disease]/not PD [progressive disease]) after restarting (systemic) treatment for melanoma
timeFrame: 5 years after inclusion
measure: Quality of life questionnaires EuroQoL EQ-5D-5
timeFrame: 5 years after inclusion
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus MC
Study officials:
References: