Clinical Pharmacokinetic Study of Lurbinectedin in Patients With Advanced Solid Tumors and Varying Degrees of Hepatic Impairment

Sponsor
PharmaMar
Study ID
NCT05101265
Phase
PHASE1
Status
Unknown

Conditions

  • Advanced Solid Tumor
  • Hepatic Impairment

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Lurbinectedin — DRUG
    Patients will receive lurbinectedin as a 1-hour (-5/+20 min) i.v. infusion on Day 1 every three weeks (q3wk), over a minimum of 100 mL dilution on 5% glucose or 0.9% sodium chloride via a central line (or a minimum of 250 mL dilution if a peripheral line is used). Of note, Cycle 2 or subsequent will be administered every q3wk (+ 48 hours). Patients will receive a maximum of two cycles: a first mandatory cycle with all study assessments followed by a second optional cycle with lurbinectedin (this last optional for patients with clinical benefit as per Investigator's criteria). After completing Cycle 2, those patients waiting for the compassionate use approval will continue on the study receiving lurbinectedin herein after until disease progression, unacceptable toxicity, consent withdrawal or while it is considered to be in their best interest, or until starting treatment with lurbinectedin under a Compassionate Use Agreement outside this study. Lurbinectedin at a 3.2 mg/m² dose.
  • Lurbinectedin — DRUG
    Patients will receive lurbinectedin as a 1-hour (-5/+20 min) i.v. infusion on Day 1 every three weeks (q3wk), over a minimum of 100 mL dilution on 5% glucose or 0.9% sodium chloride via a central line (or a minimum of 250 mL dilution if a peripheral line is used). Of note, Cycle 2 or subsequent will be administered every q3wk (+ 48 hours). Patients will receive a maximum of two cycles: a first mandatory cycle with all study assessments followed by a second optional cycle with lurbinectedin (this last optional for patients with clinical benefit as per Investigator's criteria). After completing Cycle 2, those patients waiting for the compassionate use approval will continue on the study receiving lurbinectedin herein after until disease progression, unacceptable toxicity, consent withdrawal or while it is considered to be in their best interest, or until starting treatment with lurbinectedin under a Compassionate Use Agreement outside this study. Lurbinectedin at a 1.6 mg/m² dose

Study Details

Lurbinectedin is mainly eliminated by the liver. Thus, Hepatic Impairment (HI) may alter the plasma concentrations of lurbinectedin. This study is designed to examine the PK and safety of an adjusted dose of lurbinectedin when administered to patients with HI. The results of this study may be used to support future clinical studies in patients and prescribing information in future labeling.

Key Dates

Start date
Mar 9, 2021
Status verified
Nov 2023
Primary completion
Jun 1, 2025
Completion
Jun 1, 2025

Study Design

Enrollment
24 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Normal Hepatic function cohort
    Patients in the control cohort must meet the following criteria: * Total bilirubin ≤ 1.0 x upper limit of normal (ULN) and no clinical (or histological) evidence of liver disease. * Aspartate aminotransferase (AST) ≤ 1.0 x ULN and alanine aminotransferase (ALT) ≤ 1.0 x ULN. * Albumin ≥ 3.5 g/dL. * The age, weight and CLcr should be within ±10 years, ±15 kg and ±20 mL/min of the mean of pooled HI cohort, respectively; and with a similar male/female ratio.
  • Experimental: Mild Hepatic impairment cohort
    Patients with Mild Hepatic impairment must meet the following additional criteria * Total bilirubin ≤ 1.0 x ULN and AST \> 1.0 x ULN, or * Total bilirubin \> 1.0 - ≤ 1.5 x ULN and any AST, and * Albumin ≥ 3.0 g/dL
  • Experimental: Moderate Hepatic impairment cohort
    Patients with Moderate Hepatic impairment must meet the following additional criteria * Total bilirubin \>1.5 - ≤ 3.0 x ULN and any AST, and * Albumin ≥ 2.8 g/dL
  • Experimental: Severe Hepatic impairment cohort
    Patients with Severe Hepatic impairment must meet the following additional criteria: * Total bilirubin \>3.0 x ULN and any AST, and * Albumin ≥ 2.5 g/dL

Primary Outcome Measure

Total plasma dose-normalized Cmax [ Time Frame: Preinfusion, 5 minutes before end of infusion, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 24 hours, 48 hours, 96 hours, 168 hours, 240 hours, 336 hours, and 504 hours after end of infusion ]

Central Contacts

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