Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05063318
Other study ID # PM1183-A-018-20
Secondary ID
Status Recruiting
Phase Phase 1
First received
Last updated
Start date October 7, 2020
Est. completion date December 1, 2022

Study information

Verified date September 2021
Source PharmaMar
Contact Pharma Mar, S.A.
Phone +34918234647
Email smgonzalez@pharmamar.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Prospective, open-label, two-way crossover, phase Ib drug-drug interaction study in patients with advanced solid tumors


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 11
Est. completion date December 1, 2022
Est. primary completion date November 1, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Lurbinectedin alone
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
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.

Locations

Country Name City State
Spain Fundacion Jimenez Diaz Madrid
Spain Hospital HM Sanchinarro Madrid

Sponsors (1)

Lead Sponsor Collaborator
PharmaMar

Country where clinical trial is conducted

Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary Pharmacokinetic Analysis: AUC(0-8) The primary parameter of interest for the statistical analysis will be plasma doseadjusted AUC(0-8) Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
Secondary Pharmacokinetic Analysis: AUC(0-t) The area under the concentration-time curve (AUC) will be calculated using the linear-log trapezoidal rule with extrapolation to infinity. Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
Secondary Pharmacokinetic Analysis: Cmax The maximum plasma concentration (Cmax) will be obtained directly from the experimental data. Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
Secondary 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. Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
Secondary Pharmacokinetic Analysis: Total body clearance Total body clearance (CL), calculated by dividing the administered dose by the AUC with extrapolation to infinity. Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
Secondary 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 Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
Secondary Pharmacogenetics A genotype evaluation in genes relevant for lurbinectedin metabolism and transport will be investigated and reported in an independent report in order to determine whether the observed differences between patients in PK parameters are related to these genetic features. Before treatment start along with PK sample on Day 1 of Cycle 1 (each cycle is 21 days)
See also
  Status Clinical Trial Phase
Active, not recruiting NCT04972981 - A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ADCT-901 in Participants With Selected Advanced Solid Tumors Phase 1
Completed NCT05086822 - A Study of Irinotecan Hydrochloride Liposome in Advanced Solid Tumors Phase 1
Completed NCT03260322 - A Multiple-dose Study of ASP8374, an Immune Checkpoint Inhibitor, as a Single Agent and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors Phase 1
Completed NCT02526017 - Study of Cabiralizumab in Combination With Nivolumab in Patients With Selected Advanced Cancers Phase 1
Recruiting NCT06040541 - Study of RMC-9805 in Participants With KRASG12D-Mutant Solid Tumors Phase 1
Recruiting NCT05862831 - Clinical Study of PM1003 in Phase I/IIa Treatment of Advanced Malignant Solid Tumors Phase 1/Phase 2
Recruiting NCT03641794 - Indoleamine 2,3-Dioxygenase (IDO) Inhibitor in Healthy Volunteers Phase 1
Terminated NCT03665129 - IPH5401 (Anti-C5aR) in Combination With Durvalumab in Patients With Advanced Solid Tumors Phase 1
Not yet recruiting NCT06413680 - A First-In Human (FIH) Trial to Find Out if REGN10597 is Safe and How Well it Works for Adult Participants With Advanced Solid Organ Malignancies Phase 1/Phase 2
Recruiting NCT05914116 - A Study of DB-1311 in Advanced/Metastatic Solid Tumors Phase 1/Phase 2
Completed NCT01693562 - A Phase 1/2 Study to Evaluate MEDI4736 Phase 1/Phase 2
Recruiting NCT04387916 - A Study of KC1036 in Patients With Advanced Solid Tumors Phase 1
Completed NCT04095273 - Study to Test How Well Patients With Advanced Solid Tumors Respond to Treatment With the Elimusertib in Combination With Pembrolizumab, to Find the Optimal Dose for Patients, How the Drug is Tolerated and the Way the Body Absorbs, Distributes and Discharges the Drug Phase 1
Not yet recruiting NCT03692520 - Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of SCT200 in Patients With Advanced Solid Tumors Phase 1
Completed NCT02997176 - An Open-Label Pharmacokinetics and Safety Study of Talazoparib (MDV3800) Phase 1
Recruiting NCT04446260 - A Study of SHR-A1811 in Subjects With Advanced Malignant Solid Tumors Phase 1
Recruiting NCT06239155 - A Phase I/II Study of AST-3424 in Subjects With Advanced Solid Tumors Phase 1/Phase 2
Terminated NCT02253992 - An Investigational Immuno-therapy Study to Determine the Safety of Urelumab Given in Combination With Nivolumab in Solid Tumors and B-cell Non-Hodgkin's Lymphoma Phase 1/Phase 2
Recruiting NCT06076291 - An Open-label Study of SG1827 in Subjects With Advanced Solid Tumors Phase 1
Completed NCT03545971 - A Study of IBI310 for the Treatment of Patients With Advanced Solid Tumors. Phase 1