Nivolumab Dose Optimization in Patients With a Complete, Partial or Stable Response

Melanoma Clinical Trial

— NIVOPTIMIZE  

Official title:

Nivolumab Dose Optimization in Patients With a Complete, Partial or Stable Response

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06116461
• Other study ID #: NL77343.078.21
• Status: Recruiting
• Phase: Phase 4
• Start date: January 5, 2022
• Est. completion date: January 2025

Study information

• Verified date: April 2024
• Source: Erasmus Medical Center
• Contact: Michiel Zietse, MSc
• Phone: +31642534225
• Email: michielzietse[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 34
• Est. completion date: January 2025
• Est. primary completion date: October 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• Unable to draw blood for study purposes

• Patients willing to participate or already included in the SAFE-STOP trial

Related Conditions & MeSH terms

• Melanoma

Intervention

Drug:
• Nivolumab
Participants receive three reduced doses of 240 mg every four weeks

Locations

Country	Name	City	State
Netherlands	Erasmus MC	Rotterdam	Pending

Sponsors (1)

Lead Sponsor	Collaborator
Erasmus Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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
Secondary	- PD-1 receptor occupancy in PBMCs, measured 4 weeks after 3 reduced nivolumab doses	- PD-1 receptor occupancy in PBMCs, measured 4 weeks after 3 reduced nivolumab doses	Through study completion, an average of four months
Secondary	Grade =3 adverse events (CTCAE) during reduced doses	Grade =3 adverse events (CTCAE) during reduced doses	Through study completion, an average of four months
Secondary	Number of patients with new PD during 3 reduced doses	Number of patients with new PD during 3 reduced doses	Through study completion, an average of four months