NCT03726333

Hepatic Impairment Study for Lorlatinib in Cancer Patients

A PHASE 1 STUDY TO EVALUATE THE EFFECT OF HEPATIC IMPAIRMENT ON THE PHARMACOKINETICS AND SAFETY OF LORLATINIB IN ADVANCED CANCER PATIENTS

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 1 (actual)
• Sponsor: Pfizer · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a phase 1 study in advanced cancer patients with varied hepatic functions to evaluate the potential effect of hepatic impairment on pharmacokinetics and safety of lorlatinib and provide dose recommendation for patients with hepatic impairment if possible.

Detailed description

This will be a Phase 1, open label, multi center, multiple dose, non randomized, Phase 1 clinical trial of lorlatinib in advanced cancer patients with varying degrees of hepatic impairment and necessary age , weight , and gender matched prospect normal hepatic function patients. This study is intended to evaluate the potential effect of hepatic impairments on the PK and safety of lorlatinib after daily administration of lorlatinib and to provide dosing recommendation for patients with varied degree of hepatic impairment if possible. Patients in the study will be assigned to different groups (A1, normal liver function, control for group B; A2, normal liver function, control for group C; B, mild hepatic impairment; C, moderate hepatic impairment; D, severe hepatic impairment) according to their liver function. The enrollment of approximately 76 advanced cancer patients is anticipated in this study in order to have 8 PK-evaluable patients in each of Groups A1, A2, B and C, and 6 PK-evaluable patients in Group D for final statistical analysis. Evaluable patients are those who complete the planned PK sample collection on Cycle 2 Day 1 and have no lorlatinib dose modification until completion of Cycle 2 Day 1 PK evaluation. Patients who are not evaluable for PK will be replaced. Each patient will be treated with repeated oral once daily doses of lorlatinib in 21-day cycles until disease progression, patient refusal, or unacceptable toxicity occurs. The dose schedule may be modified as necessary for individual patients according to tolerability.

Conditions

• Advanced Cancers

Interventions

Type	Name	Description
DRUG	lorlatinib	continued daily administration of 100 mg lorlatinib
DRUG	lorlatinib	continued daily administration of lorlatinib at the dose level same as Group C for the first 22 days and 100 mg QD afterwards
DRUG	lorlatinib	continued daily administration of 100 mg QD lorlatinib
DRUG	lorlatinib	continued daily administration of lorlatinib at 50 mg QD initially and may be adjusted based on PK and safety results from the initial several patients
DRUG	lorlatinib	continued daily administration of lorlatinib at the dose level determined based on preliminary PK and safety results from first several patients in Group C

Timeline

• Start date: 2020-01-14
• Primary completion: 2021-07-08
• Completion: 2021-07-08
• First posted: 2018-10-31
• Last updated: 2024-06-21
• Results posted: 2024-06-21

Locations

10 sites across 1 country: United States

Regulatory

• FDA-regulated drug study