An Open-Label, Multicenter, Pharmacokinetic Study of Lurbinectedin in Patients With Advanced Solid Tumors and Varying Degrees of Hepatic Impairment

Study Identifier:
PM1183-A-017-20
CT.gov Identifier:
NCT05101265
EudraCT Identifier:
202000278914
EU Trial (CTIS) Number:
N/A
Study Contact Information:
(210) 593-5651 or [email protected]
Recruiting

Considering participating in a START clinical trial?

Get Started

Study Summary

To evaluate the PK and safety of an adjusted dose of lurbinectedin when administered to patients with HI.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Solid Tumor
Unmapped
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I
Sex
Female & Male
Age
18+ years
Study Drug
Drug: Experimental: Normal Hepatic function cohort
Read More
Drug: Total bilirubin < or = 1.0 x upper limit of normal (ULN) and no clinical (or histological) evidence of liver disease.
Drug: Intervention:
Drug: 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.
Drug: Lurbinectedin at a 3.2 mg/m² dose.
Drug: Experimental: Mild Hepatic impairment cohort
Drug: Total bilirubin < or = 1.0 x ULN and AST > 1.0 x ULN, or
Drug: Total bilirubin >1.5 - > or = 3.0 x ULN and any AST, and
Drug: Lurbinectedin at a 1.6 mg/m² dose
Drug: Total bilirubin >3.0 x ULN and any AST, and
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting

Requirements information
Inclusion criteria
  • Voluntary signed and dated written informed consent prior to any specific study procedure.
  • Male or female with age > or = 18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS)< or = 2.
  • Life expectancy > 1 month.
  • Pathologically confirmed diagnosis of advanced solid tumors [except for primary central nervous system (CNS) tumors], for which no standard therapy exists.
  • Recovery to grade < or = 1 from drug-related adverse events (AEs) of previous treatments, excluding alopecia and/or cutaneous toxicity and/or peripheral neuropathy and/or fatigue grade = 2, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE v.5).
  • Laboratory values within fourteen days prior to registration:
  • Absolute neutrophil count (ANC) > 2.0 x 10^9/L, platelet count > 120 x 10^9/L and hemoglobin > 9.0 g/dL (patients may be transfused as clinically indicated prior to study entry).
  • Creatinine clearance (CLcr) > or= 30 mL/min (using Cockcroft and Gault's formula).
  • Creatine phosphokinase (CPK) < or =2.5 x ULN (< or = 5.0 x ULN if disease related).
  • Evidence of non-childbearing status for women of childbearing potential
  • History of alcohol abuse is permissible providing that the results of alcohol (in breath or blood) test are negative at screening.
  • Patients in the control cohort (normal hepatic function) must meet the following additional inclusion criteria (10 - 13) to be enrolled in the study:
  • Total bilirubin < or = 1.0 x upper limit of normal (ULN) and no clinical (or histological) evidence of liver disease.
  • Aspartate aminotransferase (AST)< or = 1.0 x ULN and alanine aminotransferase (ALT) < or = 1.0 x ULN.
  • Albumin < or = 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.
  • Patients with HI must meet the following additional inclusion criteria (14 - 16):
  • Patients with HI per cohort must meet:
  • a) Mild HI cohort:
  • i) Total bilirubin < or =1.0 x ULN and AST > 1.0 x ULN, or
  • ii) Total bilirubin > 1.0 - < or =1.5 x ULN and any AST, and
  • iii) Albumin > or = 3.0 g/dL
  • b) Moderate HI cohort:
  • i) Total bilirubin >1.5 - < or =3.0 x ULN and any AST, and
  • ii) Albumin > or =2.8 g/dL
  • c) Severe HI cohort:
  • i) Total bilirubin >3.0 x ULN and any AST, and
  • ii) Albumin > or = 2.5 g/dL
  • Documented liver disease and/or hepatic metastases, with physical examination, liver biopsy or hepatic ultrasound, CT scan or MRI consistent with diagnosis.
  • Stable HI, defined as no clinically significant change in the disease status within the last 14 days, as documented by the patient's recent medical history (e.g., no worsening clinical signs of HI, or no worsening of total bilirubin or prothrombin time by more than 50%).
Exclusion criteria
  • All patients who meet any of the following criteria (1 - 6) will be excluded from participating in the study:
  • Concomitant diseases/conditions:
  • History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular disease within last year.
  • Symptomatic arrhythmia or any uncontrolled arrhythmia.
  • Active infection by hepatitis B virus (HBV) or hepatitis C virus (HCV), defined as: for hepatitis B, positive test for quantitative Hepatitis B virus polymerase chain reaction (PCR or HBV-DNA+), regardless of the HBsAg; and for hepatitis C, positive test for quantitative Hepatitis C virus by PCR (or HCV-RNA+).
  • Human immunodeficiency virus (HIV)-positive patients.
  • History of Gilbert's syndrome diagnosis.
  • History of biliary sepsis in the past 2 months.
  • Patients with biliary obstruction for which a stent has been placed are eligible, provided the stent has been in place for at least 10 days prior to the first dose of lurbinectedin and the liver function has stabilized; two measurements at least 2 days apart that put the patient in the same hepatic dysfunction cohort will be accepted as evidence of stable hepatic function; there should be no evidence of biliary sepsis.
  • Active coronavirus disease of 2019 (COVID-19) disease (this includes positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in nasopharyngeal/oropharyngeal swabs or nasal swabs by PCR).
  • Symptomatic, progressive or corticosteroids-requiring documented brain metastases or leptomeningeal disease involvement. Patients with asymptomatic documented stable brain metastases not requiring corticosteroids during the last four weeks are allowed.
  • Use of (strong or moderate) inhibitors or inducers of CYP3A4 activity within three weeks prior to Day 1 of Cycle 1.
  • Less than three weeks since the last systemic anticancer therapy (investigational or standard), or less than two weeks since last radiotherapy before starting treatment of Day 1 of Cycle 1. Treatment with any other investigational product within the 30 days before Day 1 of Cycle 1.
  • Women who are pregnant or breast-feeding and fertile patients (men and women) who are not using an effective method of contraception.
  • Psychiatric illness/social situations that would limit compliance with study requirements.
  • Patients with HI (all cohorts) who meet any of the following additional criteria (7 - 9) will be excluded:
  • History of gastrointestinal hemorrhage due to esophageal varices or peptic ulcers less than one month prior to Day 1 of Cycle 1.
  • Signs of significant hepatic encephalopathy (> grade II Portal Systemic Encephalopathy).
  • Severe ascites and/or pleural effusion, except for patients at the severe HI cohort.

Clinical Study Information for Healthcare Providers

By clicking the button below you will find in-depth information about this clinical trial, including study design, primary and secondary endpoints, and more. This information is intended for healthcare professionals seeking to review the scientific and operational aspects of the study.

View Study Information

Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (CIOCC)
Madrid, Spain, 28050
Investigator
Irene Moreno
Status
Terminated/Withdrawn
Condition(s) Treated at Site
Solid Tumor
Unmapped