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

NCT06116461 | Recruiting Phase 4

• 1 other identifier: NL77343.078.21
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• - PD-1 receptor occupancy in PBMCs, measured 4 weeks after 3 reduced nivolumab doses

  Through study completion, an average of four months

• Grade ≥3 adverse events (CTCAE) during reduced doses

  Through study completion, an average of four months

• Number of patients with new PD during 3 reduced doses

  Through study completion, an average of four months

Study Arms (1)

Nivolumab

EXPERIMENTAL

Patients in the experimental arm receive three reduced nivolumab doses of 240 mg Q4W

Drug: Nivolumab

Interventions

Nivolumab DRUG

Participants receive three reduced doses of 240 mg every four weeks

Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Unable to draw blood for study purposes
• Patients willing to participate or already included in the SAFE-STOP trial

Sponsors & Collaborators

• Erasmus Medical Center: lead

Study Sites (1)

Erasmus MC

Rotterdam, Pending, Netherlands

RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Michiel Zietse, MSc

CONTACT

+31642534225; michielzietse@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 4, 2023
• First Posted: November 3, 2023
• Study Start: January 5, 2022
• Primary Completion: October 1, 2024
• Study Completion: January 1, 2025
• Last Updated: April 22, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)