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Safe Stop Ipilimumab-nivolumab (IPI-NIVO) Trial

Primary Purpose

Melanoma Stage IV, Melanoma Stage III, Immunotherapy

Status
Recruiting
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
nivolumab
Sponsored by
Erasmus Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma Stage IV

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Erasmus MCRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Early discontinuation of nivolumab

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
August 12, 2022
Last Updated
September 6, 2023
Sponsor
Erasmus Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT05652673
Brief Title
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

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2023 (Actual)
Primary Completion Date
December 1, 2025 (Anticipated)
Study Completion Date
December 1, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Erasmus Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma Stage IV, Melanoma Stage III, Immunotherapy, Toxicity, Drug

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Early discontinuation of nivolumab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
nivolumab
Intervention Description
Early discontinuation of nivolumab maintenance therapy in patients with irresectable stage III or metastatic melanoma
Primary Outcome Measure Information:
Title
Ongoing response
Description
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
Time Frame
12 months after start of ipilimumab-nivolumab combination therapy
Secondary Outcome Measure Information:
Title
Ongoing response
Description
Ongoing response at 24 months after start of first-line treatment with ipilimumab-nivolumab
Time Frame
24 months after start of treatment
Title
Disease control
Description
Disease control (CR/PR) at different time points
Time Frame
5 years after inclusion
Title
duration of response
Description
Duration of response (CR/PR) measured until progressive/recurrent disease
Time Frame
5 years after inclusion
Title
Melanoma Specific Survival rate
Description
Melanoma specific survival measured from start of first-line treatment with ipilimumab-nivolumab until melanoma related death
Time Frame
5 years after inclusion
Title
Overall Survival
Description
Overall survival (OS) measured from start of first-line treatment with ipilimumab-nivolumab until death by any cause
Time Frame
5 years after inclusion
Title
(serious) adverse events
Description
Impact of discontinuation treatment on (S)AEs
Time Frame
5 years after inclusion
Title
ORR
Description
Overall Response Rate (ORR) per RECIST v1.1 in retreated patients
Time Frame
5 years after inclusion
Title
Re-treatment
Description
Rate of re-treatment for melanoma
Time Frame
5 years after inclusion
Title
Disease control (CR/PR/SD [stable disease]/not PD [progressive disease]) after restarting (systemic) treatment for melanoma
Description
Disease control (CR/PR/SD [stable disease]/not PD [progressive disease]) after restarting (systemic) treatment for melanoma
Time Frame
5 years after inclusion
Title
Quality of life questionnaires EuroQoL EQ-5D-5
Description
Quality of life is measured using questionnaires: EuroQoL EQ-5D-5
Time Frame
5 years after inclusion

10. Eligibility

Sex
All
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Erasmus MC
City
Rotterdam
ZIP/Postal Code
3015GD
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Astrid A.M. van der Veldt, Dr.
Phone
+31107041754
Email
a.vanderveldt@erasmusmc.nl

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Safe Stop Ipilimumab-nivolumab (IPI-NIVO) Trial

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