Safe Stop ipi-nivo

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

11 Sep 2024 → ongoing

Decision date (initial)

2024-09-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516938-34-00

EudraCT number

2022-002673-28

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The primary objective of the Safe Stop IPI-NIVO Trial is the rate of ongoing response1 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 (27).

Secondary objectives 3

1. A. Patient outcomes: 1. Ongoing response2 at 24 months after start of first-line treatment with ipilimumab- nivolumab 2. Disease control (CR/PR) at different time points (see Table 1 for follow-up interval) 3. Duration of response (CR/PR) measured until progressive/recurrent disease 4: Melanoma specific survival measured from start of first-line treatment with ipilimumab-nivolumab until melanoma related death 5. Overall survival (OS) measured from start of first-line treatment with ipilimumab- nivolumab until death by any cause 6t Impact of discontinuation treatment on (S)AEs3 7. Overall Response Rate (ORR) per REC I ST v1 .1 (27) in retreated patients 8. Need and feasibility of restarting (systemic) treatment for melanoma 9. Disease control (CR/PR/SD/not PD) after restarting (systemic) treatment for melanoma
2. B. Cost-effectiveness analysis 1. Impact on productivity with respect to paid and unpaid work 2. Impact on healthcare resources 3: Impact of early discontinuation of treatment on hours of informal care
3. C. Quality of Life (Qol)

Conditions and MedDRA coding

Melanoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 18 years of age or older
2. lrresectable stage Ill or metastatic melanoma
3. Treated with at least one dose of first-line ipilimumab-nivolumab and considered to be a candidate for maintenance treatment with nivolumab: o previous systemic treatment, including ICls, in (neo)adjuvant setting for resectable melanoma is allowed o in this protocol, nivolumab maintenance is interchangeable with pembrolizumab maintenance therapy.
4. Response evaluation according to RECIST v1 .1 (27) using a diagnostic CT documenting target lesions every 12 (-2/+6) weeks from the start of ipilimumabnivolumab: o 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 o for patients with PR on a diagnostic CT at response evaluation, a low-dose CT (which is usually part of 18 FDG-PET/CT) is allowed if sufficient target lesions are measurable for response evaluation according to RECIST v1 .1 criteria (27) 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.
5. Patients should be included after first CR/PR or first confirmed CR/PR according to RECIST v1 .1 (27): o inclusion should take place no later than 5 weeks after first confirmed CR/PR o in case of SD at first response evaluation, confirmed CR/PR is required for inclusion o eligible and willing to discontinue nivolumab within 4(+1) weeks after inclusion, i.e. first CR/PR or first confirmed CR/PR. o no later than 9 months after start of treatment with ipilimumab-nivolumab
6. Presence of MRI brain for the screening of brain metastases (prior to discontinuation of ipilimumab-nivolumab)
7. Participants with previously locally treated brain metastases may participate in case they meet the following criteria: o completely asymptomatic brain metastases at inclusion o MRI of brain at baseline and for response evaluation during treatment
8. Signed and dated informed consent form

Exclusion criteria 6

1. Patients with SD/PD according to RECIST v1 .1
2. 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.
3. Presence of symptomatic brain metastases: o prior to first-line treatment with ipilimumab-nivolumab, or; o when defined as new or progressive brain metastases at the time of study entry; o 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.
4. Presence of leptomeningeal metastases;
5. - Systemic chronic steroid therapy (> 1 0mg/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 irAEs. Note: local steroids such as topical, inhaled, nasal and ophthalmic steroids are allowed.
6. 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. This comprises each and every condition or circumstance preventing the patient from showing up to the outpatient controls and/or undergoing the CT-scans, or preventing the patient from (adequately) filling out the questionnaires.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary objective of this study is the rate of ongoing response (defined as the absence of disease progression according to RECIST v1 .1 (27) or melanoma­specific mortality) at 12 months after start of treatment in patients with irresectable stage Ill or metastatic melanoma who are treated with first-line ipilimumab­nivolumab and who discontinue nivolumab therapy early (no later than 9 months after treatment commencement with ipilimumab-nivolumab) upon achieving a (confirmed) CR or PR accord

Secondary endpoints 3

1. A. Patient outcomes: 1. Ongoing response at 24 months after treatment commencement with ipilimumab-nivolumab 2. Response (CR/PR) at different time points (see Table 1 and Figure 1 for follow-up interval) 3. Duration of response (CR/PR) measured until progressive/recurrent disease 4. Melanoma specific survival measured from start of first-line treatment with ipilimumab-nivolumab until melanoma related death 5. OS measured from start of combination treatment with ipilimumab-nivolumab until death
2. B. Cost-effectiveness analysis 1. Impact on productivity with respect to paid and unpaid work 2. Impact on healthcare resource 3. Impact of early discontinuation of PD-1 blockade on hours of informal care
3. C. Quality of life assessment in patients with irresectable stage Ill or metastatic melanoma who did not start nivolumab maintenance therapy or discontinued nivolumab maintenance therapy early. Patients will fill out the Qol questionnaires at inclusion, every 12 weeks in the first year of follow up, every 4 months in year 2, every 6 months in year 3 and one set of questionnaires in year 5.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Sponsor organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Address

Dr. Molewaterplein 40

City

Rotterdam

Postcode

3015 GD

Country

Netherlands

Scientific contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

dr. A.A.M. van der Veldt

Public contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

dr. A.A.M. van der Veldt

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications