Nivolumab Dose Optimization in Patients With a Complete, Partial or Stable Response
- Registration Number
- NCT06116461
- Lead Sponsor
- Erasmus Medical Center
- Brief Summary
Patients with advanced melanoma are, amongst others, currently treated with nivolumab monotherapy or with nivolumab and ipilimumab followed by nivolumab. Even though registration studies administered nivolumab in a 3 mg/kg 2 weekly scheme, currently, nivolumab monotherapy is either administered in a 240 mg 2-weekly scheme or in a 6 mg/kg or 480 mg 4-weekly scheme. With the current dosing regimen, steady-state is achieved after approximately 5 to 6 months, whereas a tumour response is usually observed earlier in patients with metastatic melanoma. Moreover, PD-1 receptor occupancy is almost saturated above doses of 0.3 mg/kg, or at nivolumab serum levels of 10 mg/L, which is a concentration that is achieved after one treatment cycle. In melanoma patients, the additional probability on response in patients treated with 3 mg/kg compared to 1 mg/kg seems limited. PFS and OS for 3 mg/kg were not superior to 1 mg/kg. Therefore, in this study, our aim is to investigate nivolumab trough levels and pharmacokinetic parameters after 3 reduced nivolumab doses.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 34
- Age ≥ 18 years
- Advanced or metastatic melanoma
- Current treatment with nivolumab for advanced or metastatic melanoma, in a 6 mg/kg or 480 mg, 4 weekly scheme
- Documented confirmed and ongoing CR, PR or SD according to RECIST v1.1
- On treatment for at least 6 months
- Unable to draw blood for study purposes
- Patients willing to participate or already included in the SAFE-STOP trial
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Nivolumab Nivolumab Patients in the experimental arm receive three reduced nivolumab doses of 240 mg Q4W
- Primary Outcome Measures
Name Time Method Difference between the nivolumab mean trough level after 3 reduced doses (240 mg every 4 weeks) and after the first dose of 6 mg/kg or 480 mg. Through study completion, an average of four months Difference between the nivolumab mean trough level after 3 reduced doses (240 mg every 4 weeks) and after the first dose of 6 mg/kg or 480 mg.
- Secondary Outcome Measures
Name Time Method - PD-1 receptor occupancy in PBMCs, measured 4 weeks after 3 reduced nivolumab doses Through study completion, an average of four months - PD-1 receptor occupancy in PBMCs, measured 4 weeks after 3 reduced nivolumab doses
Grade ≥3 adverse events (CTCAE) during reduced doses Through study completion, an average of four months Grade ≥3 adverse events (CTCAE) during reduced doses
Number of patients with new PD during 3 reduced doses Through study completion, an average of four months Number of patients with new PD during 3 reduced doses
Trial Locations
- Locations (1)
Erasmus MC
🇳🇱Rotterdam, Pending, Netherlands