Characterize the safety, tolerability, ECG effects, pharmacokinetics and immunogenicity of anetumab ravtansine given as single agent and after inhibition of CYP3A4 and P-gp by concomitant administration of itraconazole in subjects with mesothelin-expressing advanced solid cancers
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
63
Anetumab ravtansine given IV On Day 1 of each 21-day treatment cycle Part 1: Cycle 1 Day 1: 6.5 mg/kg of body weight (BW) Cycle 2 Day 1: 0.6 mg/kg BW Part 2: Cycle 1 Day 1: 6.5 mg/kg BW Cycle 2 Day 1: 6.5 mg/kg BW (planned dose) Continuous treatment: Cycles ≥3 Day 1: 6.5 mg/kg BW once every 3 weeks (Q3W)
Itraconazole 100 mg oral capsules given by mouth Cycle 1 (Day 18): 200 mg twice daily (BID) (Days 19 - 21): 200 mg once daily (QD) Cycle 2 (Days 1-8): 200 mg QD 12 days in total (Part 1 or Part 2)
UCLA-Santa Monica Medical Center
Santa Monica, California, United States
Henry Ford Health System
Detroit, Michigan, United States
PR interval duration
ECG evaluation
Time frame: Up to 2 months per patient
QRS interval duration
ECG evaluation
Time frame: Up to 2 months per patient
QT interval duration
ECG evaluation
Time frame: Up to 2 months per patient
Abnormal T/U waves
ECG evaluation
Time frame: Up to 2 months per patient
Heart rate
ECG evaluation
Time frame: Up to 2 months per patient
Cycle 1+2 AUC (area under the plasma concentration vs. time curve from zero to infinity after single (first) dose) of BAY94-9343 analytes
Time frame: At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 10h, 24h, 48h, 168h, 336h, 480h and 504h after each dose during first 42 days of the study
Cycle 1+2 AUC(0-tlast) (AUC from time zero to the last data point > LLOQ [lower limit of quantification]) of BAY94-9343 analytes
Time frame: At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 10h, 24h, 48h, 168h, 336h, 480h and 504h after each dose during first 42 days of the study
Cycle 1+2 Cmax (maximum drug concentration in plasma after the first dose administration) of BAY94-9343 analytes
Time frame: At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 10h, 24h, 48h, 168h, 336h, 480h and 504h after each dose during first 42 days of the study
QTcF (QT interval, corrected for heart rate according to Fridericia's formula) interval duration
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Washington University School of Medicine
St Louis, Missouri, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States
Mary Crowley Medical Research Center
Dallas, Texas, United States
Blacktown Cancer & Haematology Centre
Blacktown, New South Wales, Australia
Epworth HealthCare
Richmond, Victoria, Australia
CU Saint-Luc/UZ St-Luc
Bruxelles - Brussel, Belgium
UZ Gent
Ghent, Belgium
Hôpital Henri Mondor
Créteil, France
...and 8 more locations
ECG evaluation
Time frame: Up to 2 months per patient
QTcP (QT interval, corrected for heart rate using a population-specific correction) interval duration
ECG evaluation
Time frame: Up to 2 months per patient
Incidence of serious adverse events
Time frame: Up to 6 months per patient
Incidence of non-serious adverse events
Time frame: Up to 6 months per patient
Incidence of positive anti-drug antibody titer
Time frame: Up to 6 months per patient
Incidence of neutralizing antibody titers
Time frame: Up to 6 months per patient
Cycle 3 Cmax,md (Cmax after multiple-dose administration) of BAY94-9343 analytes
Time frame: At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 168h, 336h and 504h between 43rd and 64th days of the study
Cycle 3 AUC(0-tlast)md (AUC(0-tlast) after multiple-dose administration) of BAY94-9343 analytes
Time frame: At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 168h, 336h and 504h between 43rd and 64th days of the study