Clinical Pharmacokinetic Study of Lurbinectedin in Patients With Advanced Solid Tumors and Varying Degrees of Hepatic Impairment
NCT ID: NCT05101265
Last Updated: 2023-11-27
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1
24 participants
INTERVENTIONAL
2021-03-09
2025-06-01
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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.
Lurbinectedin
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.
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
Lurbinectedin
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.
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
Lurbinectedin
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
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
Lurbinectedin
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
Interventions
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Lurbinectedin
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
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
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Male or female with age ≥ 18 years.
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
4. Life expectancy \> 1 month.
5. Pathologically confirmed diagnosis of advanced solid tumors \[except for primary central nervous system (CNS) tumors\], for which no standard therapy exists.
6. Recovery to grade ≤ 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).
7. Laboratory values within fourteen days prior to registration:
1. 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).
2. Creatinine clearance (CLcr) ≥ 30 mL/min (using Cockcroft and Gault's formula).
3. Creatine phosphokinase (CPK) ≤ 2.5 x ULN (≤ 5.0 x ULN if disease related).
8. Evidence of non-childbearing status for women of childbearing potential
9. History of alcohol abuse is permissible providing that the results of alcohol (in breath or blood) test are negative at screening.
10. Total bilirubin ≤ 1.0 x upper limit of normal (ULN) and no clinical (or histological) evidence of liver disease.
11. Aspartate aminotransferase (AST) ≤ 1.0 x ULN and alanine aminotransferase (ALT) ≤ 1.0 x ULN.
12. Albumin ≥ 3.5 g/dL.
13. 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.
14. Patients with HI per cohort must meet:
a) Mild HI cohort:
i) Total bilirubin ≤ 1.0 x ULN and AST \> 1.0 x ULN, or
ii) Total bilirubin \> 1.0 - ≤ 1.5 x ULN and any AST, and
iii) Albumin ≥ 3.0 g/dL
b) Moderate HI cohort:
i) Total bilirubin \>1.5 - ≤ 3.0 x ULN and any AST, and
ii) Albumin ≥ 2.8 g/dL
c) Severe HI cohort:
i) Total bilirubin \>3.0 x ULN and any AST, and
ii) Albumin ≥ 2.5 g/dL
15. Documented liver disease and/or hepatic metastases, with physical examination, liver biopsy or hepatic ultrasound, CT scan or MRI consistent with diagnosis.
16. 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
1. Concomitant diseases/conditions:
1. History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular disease within last year.
2. Symptomatic arrhythmia or any uncontrolled arrhythmia.
3. 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+).
4. Human immunodeficiency virus (HIV)-positive patients.
5. History of Gilbert's syndrome diagnosis.
6. History of biliary sepsis in the past 2 months.
7. 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.
8. 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).
2. 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.
3. Use of (strong or moderate) inhibitors or inducers of CYP3A4 activity within three weeks prior to Day 1 of Cycle 1.
4. 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.
5. Women who are pregnant or breast-feeding and fertile patients (men and women) who are not using an effective method of contraception.
6. 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:
7. History of gastrointestinal hemorrhage due to esophageal varices or peptic ulcers less than one month prior to Day 1 of Cycle 1.
8. Signs of significant hepatic encephalopathy (\> grade II Portal Systemic Encephalopathy).
9. Severe ascites and/or pleural effusion, except for patients at the severe HI cohort.
18 Years
ALL
No
Sponsors
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PharmaMar
INDUSTRY
Responsible Party
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Principal Investigators
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Rubin Lubomirov, MD, PhD
Role: STUDY_DIRECTOR
PharmaMar
Sara Martínez González, MD
Role: STUDY_DIRECTOR
PharmaMar
Locations
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Hospital Universitario Virgen de la Victoria
Málaga, Andalusia, Spain
Hospital Universitari Vall d'Hebron
Barcelona, Catalonia, Spain
Hospital General Universitario Gregorio Marañón
Madrid, , Spain
Hospital Universitario Ramón y Cajal
Madrid, , Spain
Hospital Universitario Fundación Jimenez Diaz
Madrid, , Spain
Hospital Universitario HM Sanchinarro
Madrid, , Spain
Countries
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Central Contacts
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Facility Contacts
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Other Identifiers
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2020-002789-14
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
PM1183-A-017-20
Identifier Type: -
Identifier Source: org_study_id