This study has been transitioned to CTIS with ID 2024-516937-10-01 check the CTIS register for the current data. The primary objective of this study is to evaluate ongoing responses in patients with advanced and metastatic melanoma who discontinue…
ID
Source
Brief title
Condition
- Skin neoplasms malignant and unspecified
- Skin neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the rate of ongoing responses (CR and PR) according to
RECIST v1.1 at 24 months after first start of nivolumab or pembrolizumab.
Secondary outcome
The secondary endpoints include:
1a. Total duration of response after first documented CR or PR followed by
treatment interruption
1b. Duration of response (CR and PR) after discontinuation of nivolumab or
pembrolizumab
2. Progression-free survival (PFS) from start of nivolumab/pembrolizumab until
first PD (PFS1)
3a. Rate of reintroduction of nivolumab/pembrolizumab upon first PD
3b. Rate of introduction of other systemic therapy (i.e. other than
nivolumab/pembrolizumab) upon first PD
4a. Best response on rechallenge with nivolumab/pembrolizumab
4b. Best tumor response after introduction of other systemic therapy (i.e.
other than monotherapy PD-1 blockade)
5a. PFS after reintroduction of nivolumab/pembrolizumab (PFS2a)
5b. PFS after introduction other systemic therapy (i.e. other than monotherapy
PD-1 blockade) (PFS2b)
6. Total PFS (PFSTotal) defined as the period from initial start of PD-1
blockade until final PD (including period after discontinuation and
(re)introduction of nivolumab/pembrolizumab or other salvage therapy)
6b. Overall survival (OS)
7. Rate of grade 3-4 adverse events (AEs) after discontinuation or
reintroduction of nivolumab/pembrolizumab
8. Change in tumor burden since the start and after early discontinuation of
PD-1 blockade
9. Change in QoL after discontinuation of PD-1 blockade
10. Change in fear of disease recurrence/progression
11. Change in productivity (paid and unpaid work) after discontinuation of PD-1
blockade
12. Change in healthcare resource (within and outside the hospital) after
discontinuation of PD-1 blockade
13. Change in hours of informal care after discontinuation of PD-1 blockade
14. QoL at disease progression and restart of systemic therapy (when applicable)
15. Change in QoL after discontinuation of radiological follow-up
Background summary
Based on the pivotal clinical trials, PD-1 blockade with nivolumab or
pembrolizumab 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 PD-1 blockade
in patients with advanced and 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 (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, early discontinuation of PD-1 blockade has not been prospectively
evaluated in clinical practice.
Study objective
This study has been transitioned to CTIS with ID 2024-516937-10-01 check the CTIS register for the current data.
The primary objective of this study is to evaluate ongoing responses in
patients with advanced and metastatic melanoma who discontinue first-line
monotherapy with nivolumab or pembrolizumab upon achieving CR or PR according
to RECIST v1.1
Study design
This is a multicenter prospectively collected single arm study in the
Netherlands. The initial protocol (v1.0, 20 October 2018) is extended with the
QoL amendment.
Intervention
Discontinuation of PD-1 blockade (nivolumab or pembrolizumab) at achieving CR
or PR.
Study burden and risks
Patients are treated and evaluated according to standard of care in the
Netherlands. As PD-1 blockade will be discontinued earlier than 2 years,
participation is 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. On
the other hand, early discontinuation may reduce the toxicity rate. However, as
an increasing number of physicians discontinues treatment on an individual
basis at achieving CR or PR, the additional risk of participation in this trial
is considered limited as compared to daily clinical practice.
's-Gravendijkwal 230
Rotterdam 3015 CE
NL
's-Gravendijkwal 230
Rotterdam 3015 CE
NL
Listed location countries
Age
Inclusion criteria
- advanced or metastatic melanoma
- current treatment with first-line nivolumab or pembrolizumab for advanced or
metastatic melanoma; previous systemic treatment, including immunotherapy, in
(neo)adjuvant setting for resectable melanoma is allowed
- documented diagnostic CT at start of PD-1 blockade with nivolumab or
pembrolizumab
• 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. In
this specific case the sponsor should be consulted.
- documented tumor response evaluation every 12 (±1) weeks according to RECIST
v1.1 (34) using a diagnostic CT as per standard practice
- presence of MRI brain for the screening of brain metastases (prior to
discontinuation of PD-1 blockade)
- willingness to discontinue nivolumab or pembrolizumab within 6 (+1) weeks
weeks after
confirmation of CR or PR before the full period of 2 years therapy
Exclusion criteria
Concomitant systemic therapies with other anti-cancer agents, e.g.
BRAF-inhibitor, anti-CTLA4 (e.g. ipilimumab), or other PD-1 blockade than
nivolumab or pembrolizumab
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 | CTIS2024-516937-10-01 |
| EudraCT | EUCTR2018-001384-23-NL |
| CCMO | NL65512.078.18 |