Immunotherapy, Melanoma Stage III, Melanoma Stage IV, Toxicity, Drug
Conditions
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
Interventions
DRUGnivolumab
Early discontinuation of nivolumab maintenance therapy in patients with irresectable stage III or metastatic melanoma
Sponsors
Erasmus Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Ongoing response | 24 months after start of treatment | Ongoing response at 24 months after start of first-line treatment with ipilimumab-nivolumab |
| 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 |
| (serious) adverse events | 5 years after inclusion | Impact of discontinuation treatment on (S)AEs |
Countries
Netherlands
Outcome results
None listed