Advanced Solid TumorPhase 1NCT05101265
Clinical Pharmacokinetic Study of Lurbinectedin in Patients With Advanced Solid Tumors and Varying Degrees of Hepatic Impairment
A Phase 1 study testing Lurbinectedin in people with Advanced Solid Tumor and Hepatic Impairment, run by PharmaMar at 6 sites in Spain.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor, Hepatic Impairment
- What is being tested?
- Lurbinectedin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 6 sitesSpain
- Study dates
- 9 Mar 2021to 1 Jun 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients must fulfill the following inclusion criteria (1 - 9) to be enrolled in the study:
- Voluntary signed and dated written informed consent prior to any specific study procedure.
- Male or female with age ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 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.
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- 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).
- 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) ≥ 30 mL/min (using Cockcroft and Gault's formula).
- Creatine phosphokinase (CPK) ≤ 2.5 x ULN (≤ 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 ≤ 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.
- Patients with HI must meet the following additional inclusion criteria (14 - 16):
- Patients with HI per cohort must meet:
- Mild HI cohort:
- 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
- Moderate HI cohort:
- Total bilirubin >1.5 - ≤ 3.0 x ULN and any AST, and
- Albumin ≥ 2.8 g/dL
- Severe HI cohort:
- Total bilirubin >3.0 x ULN and any AST, and
- Albumin ≥ 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%).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Spain6 sites, 5 recruiting
- Recruiting
Hospital Universitari Vall d'Hebron
Barcelona, Catalonia, 08035
Irene Braña Garcia, Dra, ibrana@vhio.net
- Recruiting
Hospital General Universitario Gregorio Marañón
Madrid, 28007
Antonio Calles Blanco, Dr, investigaoncomedica.hgugm@salud.madrid.org
- Active, not recruiting
Hospital Universitario Ramón y Cajal
Madrid, 28034
- Recruiting
Hospital Universitario Fundación Jimenez Diaz
Madrid, 28040
Manuel Pedregal Trujillo, Dra, Manuel.pedregal@startmadrid.com
- Recruiting
Hospital Universitario HM Sanchinarro
Madrid, 28050
Irene Moreno Candilejo, Dr, Irene.moreno@startmadrid.com
- Recruiting
Hospital Universitario Virgen de la Victoria
Málaga, Andalusia, 29010
Casilda Llácer Pérez, Dra., casilda.llacer@ibima.eu
About this study
Official title: An Open-Label, Multicenter, Pharmacokinetic Study of Lurbinectedin in Patients With Advanced Solid Tumors and Varying Degrees of Hepatic Impairment
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.
Read the detailed description
This is a prospective, open-label, parallel, phase Ib, hepatic impairment study in patients with advanced solid tumors who either have Hepatic Impairment (HI) at varying degrees (mild, moderate or severe) or qualify for the control group (normal hepatic function) according to the National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) classification criteria of HI.
- Conditions
- Advanced Solid Tumor, Hepatic Impairment
- Being tested
- Lurbinectedin
- Keywords
- Hepatic Impairment, Advanced Solid Tumor, Lurbinectedin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LurbinectedinDrug
Also called PM1183
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.
LurbinectedinDrug
Also called PM1183
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 group | Role | What they receive |
|---|---|---|
| Normal Hepatic function cohort | Experimental | 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. Receives: Drug: Lurbinectedin |
| Mild Hepatic impairment cohort | Experimental | 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 Receives: Drug: Lurbinectedin |
| Moderate Hepatic impairment cohort | Experimental | 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 Receives: Drug: Lurbinectedin |
| Severe Hepatic impairment cohort | Experimental | 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 Receives: Drug: Lurbinectedin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total plasma dose-normalized Cmax
Total plasma dose-normalized Cmax of lurbinectedin will be compared between Control (normal hepatic function) cohort and each of the Hepatic impairment cohorts
Measured: 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
Total plasma dose-normalized AUC0-48h
Total plasma dose-normalized area under curve (AUC) 0-48h of lurbinectedin will be compared between Control (normal hepatic function) cohort and each of the Hepatic impairment cohorts
Measured: 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
Total plasma dose-normalized AUC0-∞
Total plasma dose-normalized AUC0-∞ (if data do not permit so, AUC0-t will be used) of lurbinectedin will be compared between Control (normal hepatic function) cohort and each of the Hepatic impairment cohorts
Measured: 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
Secondary outcomes (19)
Total plasma dose-normalized AUC0-t
Change in dose-normalized total AUC0-t of lurbinectedin between Control (normal hepatic function) cohort and each of the Hepatic impairment cohorts will be explored.
Measured: 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
Clearance
Change in Clearance (Cl) of lurbinectedin between Control (normal hepatic function) cohort and each of the Hepatic impairment cohorts will be explored.
Measured: 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
Volume of Distribution at Steady State
Change in Volume of Distribution at Steady State (Vss) of lurbinectedin between Control (normal hepatic function) cohort and each of the Hepatic impairment cohorts will be explored.
Measured: 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
T1/2
Change in T1/2 of lurbinectedin between Control (normal hepatic function) cohort and each of the Hepatic impairment cohorts will be explored.
Measured: 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
Dose-normalized unbound AUCu,0-∞
Change in dose-normalized unbound AUCu,0-∞ of lurbinectedin between Control (normal hepatic function) cohort and each of the Hepatic impairment cohorts will be explored.
Measured: 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
Dose-normalized unbound AUCu,0-48h
Change in dose-normalized unbound AUCu,0-48h of lurbinectedin between Control (normal hepatic function) cohort and each of the Hepatic impairment cohorts will be explored.
Measured: 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
Dose-normalized unbound AUCu,0-t
Change in dose-normalized unbound AUCu,0-t of lurbinectedin between Control (normal hepatic function) cohort and each of the Hepatic impairment cohorts will be explored.
Measured: 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
Dose-normalized unbound Cu,max
Change in dose-normalized unbound Cu,max of lurbinectedin between Control (normal hepatic function) cohort and each of the HI cohorts will be explored.
Measured: 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
Unbound CLu
Change in CLu of lurbinectedin between Control (normal hepatic function) cohort and each of the Hepatic impairment cohorts will be explored.
Measured: 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
Unbound Vss,u
Change in Vss,u of lurbinectedin between Control (normal hepatic function) cohort and each of the Hepatic impairment cohorts will be explored.
Measured: 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
T1/2,u
Change in T1/2,u of lurbinectedin between Control (normal hepatic function) cohort and each of the Hepatic impairment cohorts will be explored.
Measured: 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
Ratios total AUC0-∞
Change in ratios between total AUC0-∞ of main lurbinectedin metabolites relative to parent drug between Control (normal hepatic function) cohort and each of the Hepatic impairment cohorts will be explored.
Measured: 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
Ratios AUC0-48h
Change in ratios between total AUC0-48h of main lurbinectedin metabolites relative to parent drug between Control (normal hepatic function) cohort and each of the Hepatic impairment cohorts will be explored.
Measured: 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
Ratios AUC0-t
Change in ratios between total AUC0-t of main lurbinectedin metabolites relative to parent drug between Control (normal hepatic function) cohort and each of the Hepatic impairment cohorts will be explored.
Measured: 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
Ratios Cmax
Change in ratios between total Cmax of main lurbinectedin metabolites relative to parent drug between Control (normal hepatic function) cohort and each of the Hepatic impairment cohorts will be explored.
Measured: 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
Percentage of patients with non-serious adverse events
Treatment safety (AEs) will be graded according to the NCI-CTCAE v.5.
Measured: From first infusion to the end-of-treatment visit which will be scheduled within 31 days (±10 days) after administration of the last dose of lurbinectedin
Percentage of patients with serious adverse events
Treatment safety (SAEs) will be graded according to the NCI-CTCAE v.5.
Measured: From first infusion to the end-of-treatment visit which will be scheduled within 31 days (±10 days) after administration of the last dose of lurbinectedin
Percentage of patients with Laboratory abnormalities
Laboratory abnormalities will be graded according to the NCI-CTCAE v.5.
Measured: From first infusion to the end-of-treatment visit which will be scheduled within 31 days (±10 days) after administration of the last dose of lurbinectedin
Pharmacogenetics
The presence or absence of PGt polymorphisms in genes relevant for lurbinectedin disposition (distribution, metabolism and excretion) from a single blood sample collected at any time during the trial (but preferably at the same time as the pre-treatments PK sample on Day 1 of Cycle 1), which will be stored to explain individual variability in main PK parameters in future analyses
Measured: After first cycle (21 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2021
- Study start9 Mar 2021
- Primary completion1 Jun 2025 (estimated)
- Study completion1 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This is a prospective, open-label, parallel, phase Ib, hepatic impairment study in patients with advanced solid tumors who either have HI at varying degrees (mild, moderate or severe) or qualify for the control group (normal hepatic function) according to the National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) classification criteria of HI.
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- PharmaMar
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Rubin Lubomirov, MD, PhD, Study director, PharmaMarSara Martínez González, MD, Study director, PharmaMar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05101265
- Sponsor's protocol ID
- PM1183-A-017-20
- Other IDs
- 2020-002789-14
- Status last verified
- Nov 2023
- First submitted
- 29 Sep 2021
- Last updated
- 27 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Multicenter, Pharmacokinetic Study of Lurbinectedin in Patients With Advanced Solid Tumors and Varying Degrees of Hepatic Impairment
- ClinicalTrials.gov ID
- NCT05101265
- Acronym / sponsor ID
- PM1183-A-017-20
- Conditions
- Advanced Solid Tumor, Hepatic Impairment
- Keywords
- Hepatic Impairment, Advanced Solid Tumor, Lurbinectedin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- PharmaMarIndustry (pharma, biotech, devices)
- Study start
- 9 Mar 2021 (actual)
- Primary completion
- 1 Jun 2025 (estimated)
- Study completion
- 1 Jun 2025 (estimated)
- First posted
- 1 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a prospective, open-label, parallel, phase Ib, hepatic impairment study in patients with advanced solid tumors who either have Hepatic Impairment (HI) at varying degrees (mild, moderate or severe) or qualify for the control group (normal hepatic function) according to the National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) classification criteria of HI.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- This is a prospective, open-label, parallel, phase Ib, hepatic impairment study in patients with advanced solid tumors who either have HI at varying degrees (mild, moderate or severe) or qualify for the control group (normal hepatic function) according to the National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) classification criteria of HI.
| Arm | Type | Receives |
|---|---|---|
| Normal Hepatic function cohort | Experimental | Drug: LurbinectedinPatients 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. |
| Mild Hepatic impairment cohort | Experimental | Drug: LurbinectedinPatients 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 |
| Moderate Hepatic impairment cohort | Experimental | Drug: LurbinectedinPatients 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 |
| Severe Hepatic impairment cohort | Experimental | Drug: LurbinectedinPatients 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (32 listed)
- All patients must fulfill the following inclusion criteria (1 - 9) to be enrolled in the study:
- Voluntary signed and dated written informed consent prior to any specific study procedure.
- Male or female with age ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
- Life expectancy > 1 month.
Key exclusion criteria (19 listed)
- All patients who meet any of the following criteria (1 - 6) will be excluded from participating in the study:
- Concomitant diseases/conditions:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LurbinectedinAlso: PM1183Patients 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. | Drug | Mild Hepatic impairment cohort, Normal Hepatic function cohort |
| LurbinectedinAlso: PM1183Patients 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 | Drug | Moderate Hepatic impairment cohort, Severe Hepatic impairment cohort |
Primary outcome
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
Total plasma dose-normalized Cmax of lurbinectedin will be compared between Control (normal hepatic function) cohort and each of the Hepatic impairment cohorts
Total plasma dose-normalized AUC0-48h
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
Total plasma dose-normalized area under curve (AUC) 0-48h of lurbinectedin will be compared between Control (normal hepatic function) cohort and each of the Hepatic impairment cohorts
Total plasma dose-normalized AUC0-∞
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
Total plasma dose-normalized AUC0-∞ (if data do not permit so, AUC0-t will be used) of lurbinectedin will be compared between Control (normal hepatic function) cohort and each of the Hepatic impairment cohorts
19 secondary outcomes
Total plasma dose-normalized AUC0-t
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
Clearance
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
Volume of Distribution at Steady State
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
T1/2
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
Dose-normalized unbound AUCu,0-∞
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
Dose-normalized unbound AUCu,0-48h
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
Dose-normalized unbound AUCu,0-t
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
Dose-normalized unbound Cu,max
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
Unbound CLu
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
Unbound Vss,u
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
T1/2,u
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
Ratios total AUC0-∞
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
Ratios AUC0-48h
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
Ratios AUC0-t
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
Ratios 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
Percentage of patients with non-serious adverse events
Time frame: From first infusion to the end-of-treatment visit which will be scheduled within 31 days (±10 days) after administration of the last dose of lurbinectedin
Percentage of patients with serious adverse events
Time frame: From first infusion to the end-of-treatment visit which will be scheduled within 31 days (±10 days) after administration of the last dose of lurbinectedin
Percentage of patients with Laboratory abnormalities
Time frame: From first infusion to the end-of-treatment visit which will be scheduled within 31 days (±10 days) after administration of the last dose of lurbinectedin
Pharmacogenetics
Time frame: After first cycle (21 days)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rubin Lubomirov, MD, PhD study director
PharmaMar
Sara Martínez González, MD study director
PharmaMar
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lurbinectedin in people with Advanced Solid Tumor and Hepatic Impairment, run by PharmaMar at 6 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 32 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sara Martínez González, MD (+3491 823 4647, smgonzalez@pharmamar.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the 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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2023.