- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT05063318
Clinical Trial of Lurbinectedin (PM01183) in Patients With Advanced Solid Tumors
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
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Detailní popis
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.
Typ studie
Zápis (Očekávaný)
Fáze
- Fáze 1
Kontakty a umístění
Studijní kontakt
- Jméno: Pharma Mar, S.A.
- Telefonní číslo: +34918234647
- E-mail: smgonzalez@pharmamar.com
Studijní místa
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Madrid, Španělsko, 28040
- Nábor
- Fundacion Jimenez Diaz
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Kontakt:
- Bernard Doger
- E-mail: bernard.doger@startmadrid.com
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Madrid, Španělsko, 28050
- Nábor
- Hospital HM Sanchinarro
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Kontakt:
- Dr Emiliano Calvo Aller
- E-mail: emiliano.calvo@startmadrid.com
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- 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).
- 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.
Exclusion Criteria:
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).
- 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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Crossover Assignment
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Aktivní komparátor: Sequence TR
Sequence 1 (TR)
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. |
The dose of lurbinectedin during Parts A and B will be 3.2 mg/m² for all patients when administered without itraconazole.
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.
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Aktivní komparátor: Sequence RT
Sequence 2 (RT):
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The dose of lurbinectedin during Parts A and B will be 3.2 mg/m² for all patients when administered without itraconazole.
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.
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Pharmacokinetic Analysis: AUC(0-∞)
Časové okno: Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
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The primary parameter of interest for the statistical analysis will be plasma doseadjusted AUC(0-∞)
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Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Pharmacokinetic Analysis: AUC(0-t)
Časové okno: Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
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The area under the concentration-time curve (AUC) will be calculated using the linear-log trapezoidal rule with extrapolation to infinity.
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Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
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Pharmacokinetic Analysis: Cmax
Časové okno: Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
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The maximum plasma concentration (Cmax) will be obtained directly from the experimental data.
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Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
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Pharmacokinetic Analysis: T1/2
Časové okno: Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
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Terminal half-life (T1/2) will be obtained from the terminal rate constant calculated by linear regression using at least 3 observations.
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Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
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Pharmacokinetic Analysis: Total body clearance
Časové okno: Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
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Total body clearance (CL), calculated by dividing the administered dose by the AUC with extrapolation to infinity.
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Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
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Pharmacokinetic Analysis: Volume of distribution
Časové okno: Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
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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
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Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)
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Pharmacogenetics
Časové okno: Before treatment start along with PK sample on Day 1 of Cycle 1 (each cycle is 21 days)
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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.
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Before treatment start along with PK sample on Day 1 of Cycle 1 (each cycle is 21 days)
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Spolupracovníci a vyšetřovatelé
Sponzor
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Očekávaný)
Dokončení studie (Očekávaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
- Novotvary
- Fyziologické účinky léků
- Molekulární mechanismy farmakologického působení
- Antiinfekční látky
- Inhibitory enzymů
- Hormony, hormonální náhražky a antagonisté hormonů
- Cytochrom P-450 Inhibitory CYP3A
- Inhibitory enzymu cytochromu P-450
- Antagonisté hormonů
- Antifungální látky
- Inhibitory syntézy steroidů
- Inhibitory 14-alfa demetylázy
- Itrakonazol
Další identifikační čísla studie
- PM1183-A-018-20
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
produkt vyrobený a vyvážený z USA
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