Clinical Trial of Lurbinectedin (PM01183) in Patients With Advanced Solid Tumors

NCT ID: NCT05063318

Last Updated: 2025-09-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-07
• Study Completion Date: 2022-04-21

Brief Summary

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.

Conditions

Advanced Solid Tumors

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sequence TR

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.

Group Type: ACTIVE_COMPARATOR

Lurbinectedin alone

Intervention Type: DRUG

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-administration

Intervention Type: DRUG

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.

Sequence RT

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)

Group Type: ACTIVE_COMPARATOR

Lurbinectedin alone

Intervention Type: DRUG

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-administration

Intervention Type: DRUG

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.

Interventions

Lurbinectedin alone

The dose of lurbinectedin during Parts A and B will be 3.2 mg/m² for all patients when administered without itraconazole.

Intervention Type: DRUG

Lurbinectedin+Itraconazole co-administration

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Voluntary signed and dated written informed consent prior to any specific study procedure.

2. Male or female with age ≥ 18 years.

3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 1 (App. 1).

4. Life expectancy > 3 months.

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 grade 1/2 asthenia or fatigue, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE v.5).

7. Laboratory values within fourteen days prior to Day 1 of Cycle 1

8. Left ventricular ejection fraction (LVEF) by echocardiography (ECHO) or multiple-gated acquisition (MUGA) within normal range (according to institutional standards).

9. 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.

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 requiring ongoing treatment.

3. 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+).

4. History of obstructive cholestatic liver disease (suitable for stenting procedure) or biliary sepsis in the past 2 months.

5. Known of active COVID-19 disease (this includes positive test for 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. 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).

5. Treatment with any investigational product within the 30 days before Day 1 of Cycle 1.

6. 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).

7. Psychiatric illness/social situations that would limit compliance with study requirements.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PharmaMar

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sara Martínez Gonzalez, MD

Role: STUDY_DIRECTOR

PharmaMar

Rubin Lubomirov, MD, PhD

Role: STUDY_DIRECTOR

PharmaMar

Locations

Fundacion Jimenez Diaz

Madrid, , Spain

Hospital HM Sanchinarro

Madrid, , Spain

Countries

Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

PM1183-A-018-20

Identifier Type: -

Identifier Source: org_study_id