No registrations found.
ID
Source
Brief title
Health condition
Melanoma (cutaneous)
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of this study is the rate of ongoing response according to RECIST v1.1 at 24-months (from first start of treatment with PD-1 blockade).
Secondary outcome
The secondary endpoints include best overall response, duration of response after discontinuation of PD-1 blockade, the need and outcome of rechallenge with PD-1 blockade, and changes in SAE(s). After discontinuation of PD-1 blockade, changes in HRQoL (FACT-M, EuroQol EQ-5D, CWS) will be measured at different time points and compared with patients without early discontinuation of PD-1 blockade. In addition, measurements will be performed to determine the impact of treatment discontinuation on healthcare resource use, productivity losses (RUQ-M by iMTA), and hours of informal care.
Background summary
Rationale: 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
We hypothesize that it is safe to stop first-line nivolumab or pembrolizumab at confirmed response, while improving quality of life (QoL) and reducing the use of healthcare resources, and costs.
Study design
See above
Intervention
Discontinuation of PD-1 blockade (nivolumab or pembrolizumab) at achieving confirmed CR or PR.
Inclusion criteria
For final inclusion in the trial, patients need to have a confirmed CR/PR according to RECIST v1.1 using a diagnostic CT, including a diagnostic CT at baseline
A potential subject who meets the following criteria can be screened for inclusion in this study:
- age ≥ 18 year
- 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
o Please note: if one of the PD-1 blockade treatments is replaced by the other because of a reason other than progression or non-response, e.g. because of infusion-related reactions, this is still considered first-line therapy and patients are still eligible for inclusion
- documented target lesion(s) according to RECIST v1.1 on diagnostic CT at start of PD-1 blockade with nivolumab or pembrolizumab
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. In this specific case, the sponsor should be consulted.
- documented tumor response evaluation every 12(+/-1) weeks according to RECIST v1.1 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)
- planned and willing to discontinue nivolumab or pembrolizumab within 6(+1) weeks after first confirmation of CR or PR before the full period of 2 years therapy
- signed and dated informed consent form
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
IPD sharing statement
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 |
|---|---|
| NTR-new | NL7293 |
| NTR-old | NTR7502 |
| Other | MEC-2018-114/NL65512.078.18 : EudraCT: 2018-001384-23 |