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

Conditions

Lurbinectedin alone — 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 — 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.

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

Active Comparator: 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.
Active Comparator: 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)

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) ]