Safe Stop Ipilimumab-nivolumab (IPI-NIVO) Trial

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

Study Overview

• Status: Recruiting
• Conditions: Immunotherapy; Melanoma Stage IV; Melanoma Stage III; Toxicity, Drug
• Intervention / Treatment: Drug: nivolumab

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Rotterdam, Netherlands, 3015GD
    • Recruiting
    • Erasmus MC
    • Contact: Astrid A.M. van der Veldt, Dr.; Phone Number: +31107041754; Email: a.vanderveldt@erasmusmc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early discontinuation of nivolumab	Drug: nivolumab; Early discontinuation of nivolumab maintenance therapy in patients with irresectable stage III or metastatic melanoma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	12 months after start of ipilimumab-nivolumab combination therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ongoing response	Ongoing response at 24 months after start of first-line treatment with ipilimumab-nivolumab	24 months after start of treatment
Disease control	Disease control (CR/PR) at different time points	5 years after inclusion
duration of response	Duration of response (CR/PR) measured until progressive/recurrent disease	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	5 years after inclusion
Overall Survival	Overall survival (OS) measured from start of first-line treatment with ipilimumab-nivolumab until death by any cause	5 years after inclusion
(serious) adverse events	Impact of discontinuation treatment on (S)AEs	5 years after inclusion
ORR	Overall Response Rate (ORR) per RECIST v1.1 in retreated patients	5 years after inclusion
Re-treatment	Rate of re-treatment for melanoma	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	5 years after inclusion
Quality of life questionnaires EuroQoL EQ-5D-5	Quality of life is measured using questionnaires: EuroQoL EQ-5D-5	5 years after inclusion

Collaborators and Investigators

• Sponsor: Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: August 12, 2022
• First Submitted That Met QC Criteria: December 14, 2022
• First Posted (Actual): December 15, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 26, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Chemically-Induced Disorders; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma; Drug-Related Side Effects and Adverse Reactions; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Nivolumab
• Other Study ID Numbers: NL82177.078.22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No