Melanoma Stage IVNCT05652673
Safe Stop Ipilimumab-nivolumab (IPI-NIVO) Trial
A study testing nivolumab in people with Melanoma Stage IV and Melanoma Stage III, run by Erasmus Medical Center at 1 site in Netherlands.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma Stage IV, Melanoma Stage III, Immunotherapy
- What is being tested?
- nivolumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Feb 2023to 1 Dec 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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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
- 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
Who cannot join
- 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.
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- (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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Erasmus MC
Rotterdam, 3015GD
Astrid A.M. van der Veldt, Dr., +31107041754, a.vanderveldt@erasmusmc.nl
About this study
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
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
- Conditions
- Melanoma Stage IV, Melanoma Stage III, Immunotherapy, Toxicity, Drug
- Being tested
- nivolumab
- Medical subject headings
- Melanoma, Drug-Related Side Effects and Adverse Reactions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nivolumabDrug
Early discontinuation of nivolumab maintenance therapy in patients with irresectable stage III or metastatic melanoma
| Study group | Role | What they receive |
|---|---|---|
| Early discontinuation of nivolumab | Experimental | Not described Receives: Drug: nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ongoing response
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
Measured: 12 months after start of ipilimumab-nivolumab combination therapy
Secondary outcomes (10)
Ongoing response
Ongoing response at 24 months after start of first-line treatment with ipilimumab-nivolumab
Measured: 24 months after start of treatment
Disease control
Disease control (CR/PR) at different time points
Measured: 5 years after inclusion
duration of response
Duration of response (CR/PR) measured until progressive/recurrent disease
Measured: 5 years after inclusion
Melanoma Specific Survival rate
Melanoma specific survival measured from start of first-line treatment with ipilimumab-nivolumab until melanoma related death
Measured: 5 years after inclusion
Overall Survival
Overall survival (OS) measured from start of first-line treatment with ipilimumab-nivolumab until death by any cause
Measured: 5 years after inclusion
(serious) adverse events
Impact of discontinuation treatment on (S)AEs
Measured: 5 years after inclusion
ORR
Overall Response Rate (ORR) per RECIST v1.1 in retreated patients
Measured: 5 years after inclusion
Re-treatment
Rate of re-treatment for melanoma
Measured: 5 years after inclusion
Disease control (CR/PR/SD [stable disease]/not PD [progressive disease]) after restarting (systemic) treatment for melanoma
Disease control (CR/PR/SD [stable disease]/not PD [progressive disease]) after restarting (systemic) treatment for melanoma
Measured: 5 years after inclusion
Quality of life questionnaires EuroQoL EQ-5D-5
Quality of life is measured using questionnaires: EuroQoL EQ-5D-5
Measured: 5 years after inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2022
- Study start1 Feb 2023
- Primary completion1 Dec 2025 (estimated)
- Study completion1 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Melanoma Stage IVStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, A.A.M. van der Veldt, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05652673
- Sponsor's protocol ID
- NL82177.078.22
- Status last verified
- Feb 2025
- First submitted
- 12 Aug 2022
- Last updated
- 28 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
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 complete or partial response in patients with irresectable stage III or metastatic melanoma treated with first-line ipilimumab-nivolumab - study protocol. BMC Cancer. 2024 May 23;24(1):632. doi: 10.1186/s12885-024-12336-0.
PubMed 38783238
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05652673
- Acronym / sponsor ID
- NL82177.078.22
- Conditions
- Melanoma Stage IV, Melanoma Stage III, Immunotherapy, Toxicity, Drug
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Study start
- 1 Feb 2023 (actual)
- Primary completion
- 1 Dec 2025 (estimated)
- Study completion
- 1 Dec 2029 (estimated)
- First posted
- 15 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Early discontinuation of nivolumab | Experimental | Drug: nivolumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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:
- 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:
- Patients should be included after first CR/PR or first confirmed CR/PR according to RECIST v1.1 30:
Key exclusion criteria (10 listed)
- 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:
- (provided that the other in- and exclusion criteria are met);
- Presence of leptomeningeal metastases;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| nivolumabEarly discontinuation of nivolumab maintenance therapy in patients with irresectable stage III or metastatic melanoma | Drug | Early discontinuation of nivolumab |
Primary outcome
Ongoing response
Time frame: 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
10 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2025.
- Derived from this study: PubMed 38783238Janssen 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 complete or partial response in patients with irresectable stage III or metastatic melanoma treated with first-line ipilimumab-nivolumab - study protocol. BMC Cancer. 2024 May 23;24(1):632. doi: 10.1186/s12885-024-12336-0.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing nivolumab in people with Melanoma Stage IV and Melanoma Stage III, run by Erasmus Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ongoing response (time frame: 12 months after start of ipilimumab-nivolumab combination therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05652673, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2025.