Advanced Solid TumorsPhase 1NCT05063318
Clinical Trial of Lurbinectedin (PM01183) in Patients With Advanced Solid Tumors
A Phase 1 study testing Lurbinectedin alone and Lurbinectedin+Itraconazole co-administration in people with Advanced Solid Tumors, run by PharmaMar at 2 sites in Spain.
Trial summary
Prospective, open-label, two-way crossover, phase Ib drug-drug interaction study in patients with advanced solid tumors Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors
- What is being tested?
- Lurbinectedin alone and Lurbinectedin+Itraconazole co-administration
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 2 sitesSpain
- Study dates
- 7 Oct 2020to 21 Apr 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- 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) of ≤ 1 (App. 1).
- Life expectancy > 3 months.
- Pathologically confirmed diagnosis of advanced solid tumors [except for primary central nervous system (CNS) tumors], for which no standard therapy exists.
- Recovery to grade ≤ 1 from drug-related adverse events (AEs) of previous treatments, excluding alopecia and grade 1/2 asthenia or fatigue, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE v.5).
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- Laboratory values within fourteen days prior to Day 1 of Cycle 1
- Left ventricular ejection fraction (LVEF) by echocardiography (ECHO) or multiple-gated acquisition (MUGA) within normal range (according to institutional standards).
- Evidence of non-childbearing status for women of childbearing potential (WOCBP). WOCBP must agree to use a highly effective contraceptive measure up to six months after treatment discontinuation. Valid methods to determine the childbearing potential, adequate contraception and requirements for WOCBP partners are described in App. 2. Fertile male patients with WOCBP partners should use condoms during treatment and for four months following the last investigational medicinal product (IMP) dose.
Who cannot join
- 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 requiring ongoing treatment.
- Known cirrhosis, alcohol induced steatosis, or chronic active hepatitis. For hepatitis B, this includes positive test for both Hepatitis B surface antigen (HBsAg) and quantitative Hepatitis B polymerase chain reaction (PCR or HVB-DNA+). For hepatitis C, this includes positive test for both Hepatitis C antibody and quantitative Hepatitis C by PCR (or HVC-RNA+).
- History of obstructive cholestatic liver disease (suitable for stenting procedure) or biliary sepsis in the past 2 months.
- Known of active COVID-19 disease (this includes positive test for SARS-CoV- 2 in nasopharyngeal/oropharyngeal swabs or nasal swabs by PCR).
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- 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.
- Use of CYP3A4 substrates such as HMG-CoA reductase inhibitors such as atorvastatin, lovastatin and simvastatin for which concomitant administration with strong CYP3A4 inhibitor is contraindicated (App 3).
- Treatment with any 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 (see App 2).
- Psychiatric illness/social situations that would limit compliance with study requirements.
Trial locations and contacts
2 sites in 1 country.
Spain2 sites
Fundacion Jimenez Diaz
Madrid, 28040
Hospital HM Sanchinarro
Madrid, 28050
About this study
Official title: An Open-Label, Multicenter Study to Assess the Potential Effects of Itraconazole (a Strong CYP3A4 Inhibitor) on the Pharmacokinetics of Lurbinectedin (PM01183) in Patients With Advanced Solid Tumors
Prospective, open-label, two-way crossover, phase Ib drug-drug interaction study in patients with advanced solid tumors
Read the detailed description
Prospective, open-label, two-way crossover, phase Ib drug-drug interaction study in patients with advanced solid tumors.
The study will include a pre-treatment (screening) phase (within 14 days before the first lurbinectedin or itraconazole administration) followed by a treatment phase consisting of two lurbinectedin cycles, one cycle in combination with itraconazole and one cycle as single agent (in different order depending on the study sequence), and one additional third cycle of lurbinectedin as a single agent for patients who meet the continuation criteria and obtain a clinical benefit after the first two cycles, and then follow-up of adverse events if any.
- Conditions
- Advanced Solid Tumors
- Being tested
- Lurbinectedin alone, Lurbinectedin+Itraconazole co-administration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lurbinectedin aloneDrug
The dose of lurbinectedin during Parts A and B will be 3.2 mg/m² for all patients when administered without itraconazole.
Lurbinectedin+Itraconazole co-administrationDrug
The dose of lurbinectedin when given in combination with itraconazole for the initial three patients in Part A will be 0.8 mg/m², and in Part B is susceptible to be adjusted properly if deemed necessary based on exposure and safety experience in Part A.
| Study group | Role | What they receive |
|---|---|---|
| Sequence TR | Active comparator | Sequence 1 (TR)
* Cycle 1: Itraconazole + lurbinectedin 0.8 mg/m²
* Cycle 2: Lurbinectedin alone 3.2 mg/m²
* Cycle 3: Lurbinectedin alone 3.2 mg/m² (optional)
PART A The dose of lurbinectedin when given in combination with itraconazole for the initial three patients in Part A will be 0.8 mg/m². In Part A, all patients will receive itraconazole plus lurbinectedin in Cycle 1 and lurbinectedin alone in Cycles 2 and 3 (this last cycle being optional).
PART B Randomization will apply for study Part B only. In Part B is susceptible to be adjusted properly if deemed necessary based on exposure and safety experience in Part A. In Part B, patients will be randomly assigned to the corresponding sequences. Receives: Drug: Lurbinectedin alone; Drug: Lurbinectedin+Itraconazole co-administration |
| Sequence RT | Active comparator | Sequence 2 (RT):
* Cycle 1: Lurbinectedin alone 3.2 mg/m²
* Cycle 2: Itraconazole + lurbinectedin 0.8 mg/m²
* Cycle 3: Lurbinectedin alone 3.2 mg/m² (optional) Receives: Drug: Lurbinectedin alone; Drug: Lurbinectedin+Itraconazole co-administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic Analysis: Dose-adjusted AUC(0-∞)
The primary parameter of interest for the statistical analysis will be plasma dose adjusted AUC(0-∞)
Measured: Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
Secondary outcomes (5)
Pharmacokinetic Analysis: Dose-normalized AUC(0-t)
The dose-normalized area under the concentration-time curve (AUC) will be calculated using the linear-log trapezoidal rule with extrapolation to infinity.
Measured: Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
Pharmacokinetic Analysis: Dose-normalized Cmax
The maximum dose-normalized plasma concentration (Cmax) will be obtained directly from the experimental data.
Measured: Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
Pharmacokinetic Analysis: T1/2
Terminal half-life (T1/2) will be obtained from the terminal rate constant calculated by linear regression using at least 3 observations.
Measured: Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
Pharmacokinetic Analysis: Total Body Clearance (CL)
Total body clearance (CL), calculated by dividing the administered dose by the AUC with extrapolation to infinity.
Measured: Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
Pharmacokinetic Analysis: Volume of Distribution
Volume of distribution (both at steady state and based on the terminal phase) (Vss and Vz, respectively): Vss is an estimate that equals mean residence time times total body clearance. Vz, calculated dividing the administered dose by the product of the AUC with extrapolation to infinity by the terminal rate constant
Measured: Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 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 Oct 2021
- Study start7 Oct 2020
- Primary completion21 Apr 2022
- Study completion21 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Advanced Solid TumorsStudies 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
- Randomised
- Intervention model
- Crossover
- Model description
- This is a prospective, open-label, two-way crossover, phase Ib drug-drug interaction study in patients with advanced solid tumors.
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- PharmaMar
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sara Martínez Gonzalez, MD, Study director, PharmaMarRubin Lubomirov, MD, PhD, Study director, PharmaMar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05063318
- Sponsor's protocol ID
- PM1183-A-018-20
- Status last verified
- Aug 2025
- First submitted
- 2 Sep 2021
- Last updated
- 2 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Multicenter Study to Assess the Potential Effects of Itraconazole (a Strong CYP3A4 Inhibitor) on the Pharmacokinetics of Lurbinectedin (PM01183) in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT05063318
- Acronym / sponsor ID
- PM1183-A-018-20
- Conditions
- Advanced Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- PharmaMarIndustry (pharma, biotech, devices)
- Study start
- 7 Oct 2020 (actual)
- Primary completion
- 21 Apr 2022 (actual)
- Study completion
- 21 Apr 2022 (actual)
- First posted
- 1 Oct 2021 (actual)
- Results
- Posted 2 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Prospective, open-label, two-way crossover, phase Ib drug-drug interaction study in patients with advanced solid tumors
Detailed description
Prospective, open-label, two-way crossover, phase Ib drug-drug interaction study in patients with advanced solid tumors.
The study will include a pre-treatment (screening) phase (within 14 days before the first lurbinectedin or itraconazole administration) followed by a treatment phase consisting of two lurbinectedin cycles, one cycle in combination with itraconazole and one cycle as single agent (in different order depending on the study sequence), and one additional third cycle of lurbinectedin as a single agent for patients who meet the continuation criteria and obtain a clinical benefit after the first two cycles, and then follow-up of adverse events if any.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a prospective, open-label, two-way crossover, phase Ib drug-drug interaction study in patients with advanced solid tumors.
| Arm | Type | Receives |
|---|---|---|
| Sequence TR | Active comparator | Drug: Lurbinectedin alone, Drug: Lurbinectedin+Itraconazole co-administrationSequence 1 (TR) * Cycle 1: Itraconazole + lurbinectedin 0.8 mg/m² * Cycle 2: Lurbinectedin alone 3.2 mg/m² * Cycle 3: Lurbinectedin alone 3.2 mg/m² (optional) PART A The dose of lurbinectedin when given in combination with itraconazole for the initial three patients in Part A will be 0.8 mg/m². In Part A, all patients will receive itraconazole plus lurbinectedin in Cycle 1 and lurbinectedin alone in Cycles 2 and 3 (this last cycle being optional). PART B Randomization will apply for study Part B only. In Part B is susceptible to be adjusted properly if deemed necessary based on exposure and safety experience in Part A. In Part B, patients will be randomly assigned to the corresponding sequences. |
| Sequence RT | Active comparator | Drug: Lurbinectedin alone, Drug: Lurbinectedin+Itraconazole co-administrationSequence 2 (RT): * Cycle 1: Lurbinectedin alone 3.2 mg/m² * Cycle 2: Itraconazole + lurbinectedin 0.8 mg/m² * Cycle 3: Lurbinectedin alone 3.2 mg/m² (optional) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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) of ≤ 1 (App. 1).
- Life expectancy > 3 months.
- Pathologically confirmed diagnosis of advanced solid tumors [except for primary central nervous system (CNS) tumors], for which no standard therapy exists.
Key exclusion criteria (12 listed)
- 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.
- Use of CYP3A4 substrates such as HMG-CoA reductase inhibitors such as atorvastatin, lovastatin and simvastatin for which concomitant administration with strong CYP3A4 inhibitor is contraindicated (App 3).
- Treatment with any 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 |
|---|---|---|
| Lurbinectedin aloneThe dose of lurbinectedin during Parts A and B will be 3.2 mg/m² for all patients when administered without itraconazole. | Drug | Sequence RT, Sequence TR |
| Lurbinectedin+Itraconazole co-administrationThe dose of lurbinectedin when given in combination with itraconazole for the initial three patients in Part A will be 0.8 mg/m², and in Part B is susceptible to be adjusted properly if deemed necessary based on exposure and safety experience in Part A. | Drug | Sequence RT, Sequence TR |
Primary outcome
Pharmacokinetic Analysis: Dose-adjusted AUC(0-∞)
Time frame: Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
The primary parameter of interest for the statistical analysis will be plasma dose adjusted AUC(0-∞)
5 secondary outcomes
Pharmacokinetic Analysis: Dose-normalized AUC(0-t)
Time frame: Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
Pharmacokinetic Analysis: Dose-normalized Cmax
Time frame: Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
Pharmacokinetic Analysis: T1/2
Time frame: Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
Pharmacokinetic Analysis: Total Body Clearance (CL)
Time frame: Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
Pharmacokinetic Analysis: Volume of Distribution
Time frame: Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Sara Martínez Gonzalez, MD study director
PharmaMar
Rubin Lubomirov, MD, PhD study director
PharmaMar
2 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 alone and Lurbinectedin+Itraconazole co-administration in people with Advanced Solid Tumors, run by PharmaMar at 2 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 9 inclusion and 12 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: finished, as of the sponsor's last update on 2 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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?
Yes. Results are posted in the registry (first posted 2 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetic Analysis: Dose-adjusted AUC(0-∞) (time frame: Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)). 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 2 Sep 2025.