Copanlisib (BAY80-6946) Drug-drug Interaction and Cardiovascular Safety Study in Advanced Solid Tumour Patients

Official Title

An Open-label Non-randomized, Phase 1 Study to Evaluate the Effect of (a) Itraconazole or Rifampin on the Pharmacokinetics of a Single Intravenous Dose of Copanlisib and (b) Copanlisib on Cardiovascular Safety in Subjects With Advanced Solid Tumours

Summary:

In summary, copanlisib is metabolized mainly by the CYP3A4 enzyme, thus a study to evaluate potential DDI (drug-drug interaction) of copanlisib with concomitant CYP3A4 modulators such as Itraconazole (CYP3A4 inhibitor) and Rifampin (CYP3A4 inducer) is necessary. With this regard this study aims to evaluate the effect of Itraconazole or Rifampin on the absorbtion, distribution, metabolization and elimination of Copanlisib (BAY80-6946) . In addition, as parameters of cardiovascular safety , the effect of copanlisib on the heart's ability to pump blood and to rule out copanlisib's potential for causing a specific type of life-threatening arrhythmia, QT/QTc intervals and left ventricular ejection fraction will be evaluated.

Trial Description

Primary Outcome:

  • Area under the curve of Copanlisib [AUC (0-168)]
  • Area under the curve of Copanlisib [AUC (0-168)] with Itraconazole
  • AUC (0-168) of Copanlisib with Rifampin
  • Area under the curve of Copanlisib (AUC)
  • Area under the curve of Copanlisib (AUC) with Itraconazole
  • AUC of Copanlisib with Rifampin
  • Maximum concentration attained after dosing (Cmax) of Copanlisib
  • Maximum concentration attained after dosing (Cmax) of Copanlisib with Itraconazole
  • Maximum concentration attained after dosing (Cmax) of Copanlisib with Rifampin
  • Time-matched largest change of QT interval (Frederica's correction) [QTcF] after dosing of Copanlisip
Secondary Outcome:
  • Area under the curve from dosing to last measurement [AUC(0-tlast)] of Copanlisib
  • Area under the curve from dosing to last measurement [AUC(0-tlast)] of Copanlisib with Itraconazole
  • Area under the curve from dosing to last measurement [AUC(0-tlast)] of Copanlisib with Rifampin
  • Time from dosing to attainment of Cmax (tmax) of Copanlisib
  • Time from dosing to attainment of Cmax (tmax) of Copanlisib with Itraconazole
  • Time from dosing to attainment of Cmax (tmax) of Copanlisib with Rifampin
  • Time from dosing to last measurement (tlast) of Copanlisib
  • Time from dosing to last measurement (tlast) of Copanlisib with Itraconazole
  • Time from dosing to last measurement (tlast) of Copanlisib with Rifampin
  • Terminal half-life (t1/2) of Copanlisib
  • Terminal half-life (t1/2) of Copanlisib with Itraconazole
  • Terminal half-life (t1/2) of Copanlisib with Rifampin
  • Urine [AE,ur(0-24)] after dosing of Copanlisib
  • Urine [AE,ur(0-24)] after dosing of Copanlisib with Itraconazole
  • Urine [AE,ur(0-24)] after dosing of Copanlisib with Rifampin
  • Number of participants with adverse events as a measure of safety and tolerability of Copanlisib
  • Effect of Copanlisib on PR intervals
  • Effect of Copanlisib on QRS intervals
  • Effect of Copanlisib on ECG waveform morphology
  • Effect of Copanlisib on left ventricular ejection fraction (LVEF)
The PI3K/AKT/mammalian target of rapamycin (mTOR) pathway is one of the prominent pathways that promote cellular survival and constitutively is activated in many types of cancer. Class I PI3K receptor is downstream of most cancer associated tyrosine kinase growth factor receptors. PI3K inhibitors are expected to be effective not only in PI3K pathway-driven tumours but also in combination with other chemotherapy agents. The management of metabolic effects is an issue that must be addressed in the development of anticancer agents targeting the PI3K-Akt-mTOR pathway. Copanlisib (BAY 80-6946) is a novel PI3K inhibitor being developed for the treatment of advanced and refractory malignancies.

View this trial on ClinicalTrials.gov

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Resources

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