This study has been transitioned to CTIS with ID 2024-516938-34-00 check the CTIS register for the current data. The primary objective of this study is to evaluate the rate of ongoing response at 12 months after start of treatment in patients with…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
- Skin neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint of this study is response rate, defined as the rate of ongoing
responses (CR and PR) according to RECIST v1.1 at 12 months after first start
of first-line ipilimumab-nivolumab in patients with irresectable stage III or
metastatic melanoma.
Secondary outcome
The secondary objectives of this study include the evaluation of:
A. Patient outcomes:
1. Ongoing response at 24 months after start of first-line treatment with
ipilimumab-nivolumab
2. Response (CR/PR) at different time points
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
6. Impact of discontinuation treatment on (S)AEs
7. Overall Response Rate (ORR) per RECIST v1.1 in retreated patients
8. Need and feasibility of restarting (systemic) treatment for melanoma
9. Disease control (CR/PR/SD/not PD) after restarting (systemic) anti-melanoma
treatment
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 treatment on hours of informal care
C. Quality of life assessment in patients with irresectable stage III 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.
Background summary
Based on the pivotal clinical trials, combination therapy with ipilimumab and
nivolumab is usually discontinued in case of disease progression, severe
toxicity, or after a treatment duration of maximum 2 years. However, durable
tumor responses have been observed after early discontinuation of the
ipilimumab-nivolumab schedule in patients with irresectable stage III or
metastatic melanoma who achieve a tumor response. In clinical practice, an
increasing number of physicians discontinues treatment on an individual basis,
for example at achieving complete response (CR) or partial response (PR), or on
patients* request. From a toxicity, economic, and patient perspective, a
shorter treatment duration is obviously to be preferred, however, the safety of
early discontinuation of the ipilimumab-nivolumab schedule has not been
prospectively evaluated in clinical practice.
Study objective
This study has been transitioned to CTIS with ID 2024-516938-34-00 check the CTIS register for the current data.
The primary objective of this study is to evaluate the rate of ongoing response
at 12 months after start of treatment in patients with irresectable stage III
or metastatic melanoma who are treated with first-line ipilimumab-nivolumab and
who early discontinue treatment upon achieving a (confirmed) CR or PR according
to RECIST v1.1.
Study design
This is a nationwide, multicentre, prospective, single-arm, intervention study
in the Netherlands.
Intervention
Discontinuation of (maintenance) treatment with nivolumab at achieving CR
Study burden and risks
Patients are treated and evaluated according to standard of care in the
Netherlands. As nivolumab will be discontinued early, participation in this
trial may affect treatment efficacy, which will be evaluated as primary
objective of this study. As a result, participation in this trial may affect
clinical outcome and even survival of these patients. However, as an increasing
number of physicians discontinues this treatment early (before 2 years) on an
individual basis at achieving (confirmed) CR or PR, the additional risk of
participation in this trial is considered limited as compared to daily clinical
practice.
Dr. Molewaterplein 40
Rotterdam 3015GD
NL
Dr. Molewaterplein 40
Rotterdam 3015GD
NL
Listed location countries
Age
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.
o Previous systemic treatment, including ICIs, in (neo)adjuvant setting for
resectable melanoma is allowed
o In this protocol, nivolumab maintenance is interchangeable with pembrolizumab
maintenance therapy.
- Response evaluation according to RECIST v1.1 using a diagnostic CT
documenting target lesions every 12 (-2/+6) weeks from the start of
ipilimumab-nivolumab;
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 18FDG-PET/CT) is allowed if sufficient target lesions
are measurable for response evaluation according to RECIST v1.1 criteria.
o In case of asymptomatic brain metastases prior to start of first-line
ipilimumab-nivolumab, intracerebral tumor response should be confirmed using an
MRI prior to inclusion
- Patients should be included after first CR/PR or first confirmed CR/PR
according to RECIST v1.1
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
- 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:
o completely asymptomatic brain metastases at inclusion
o 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 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. 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-516938-34-00 |
| EudraCT | EUCTR2022-002673-28-NL |
| CCMO | NL82177.078.22 |