Anetumab ravtansine is developed for the treatment of patients with recurrent platinum-resistant ovarian cancer. The purpose of the proposed trial is to identify the maximum tolerated dose of anetumab ravtansine that could be safely combined with pegylated liposomal doxorubicin in this indication.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
65
Anetumab ravtansine will be administered on Day 1 of every 21-day treatment cycle.
Pegylated liposomal doxoribicin will be administered on Day 1 of every 21-day treatment cycle.
Rocky Mountain Cancer Centers
Aurora, Colorado, United States
Yale University School of Medicine
New Haven, Connecticut, United States
Oklahoma University Health Science Center
Oklahoma City, Oklahoma, United States
UZ Leuven Gasthuisberg
Maximum tolerated dose (MTD) of Anetumab ravtansine in combination with pegylated liposomal doxorubicin when given every three weeks
MTD is defined as the highest dose of anetumab ravtansine administered in combination with pegylated liposomal doxorubicin that can be given such that not more than 1 of 6 subjects at a given dose level experiences a dose-limiting toxicity (DLT).
Time frame: Up to 6 months, minimum: 1 cycle (=21days)
Incidence of serious and non-serious adverse events (AEs)
Time frame: Up to 6 months
AUC (area under the plasma concentration vs. time curve from zero to infinity after single (first) dose) of Anetumab ravtansine analytes (Antibody drug conjugates, Total Antibody, metabolites DM4, and DM4-Me)
Time frame: At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 24h, 48h, 168h, 336h and 504h post-dose, beginning on day 1 of cycle 1
AUC(0-tlast) (AUC from time zero to the last data point > lower limit of quantification) of Anetumab ravtansine analytes (Antibody drug conjugates, Total Antibody, metabolites DM4, and DM4-Me)
Time frame: At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 24h, 48h, 168h, 336h and 504h post-dose, beginning on day 1 of cycle 1
Cmax (maximum drug concentration in plasma after first dose administration) of Anetumab ravtansine analytes (Antibody drug conjugates, Total Antibody, metabolites DM4, and DM4-Me)
Time frame: At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 24h, 48h, 168h, 336h and 504h post-dose, beginning on day 1 of cycle 1
AUC of total pegylated liposomal doxorubicin
Time frame: At pre-dose, 0.5h, 1h, 2h, 3h, 6h, 8h, 22h, 46h, and 166h post-dose , beginning on day 1 of cycle 1
AUC(0-tlast) of total pegylated liposomal doxorubicin
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Leuven, Belgium
The Institute of Oncology
Chisinau, Moldova
Ciutat Sanitària i Universitaria de la Vall d'Hebron
Barcelona, Spain
Clinica Universidad de Navarra CUN en Madrid
Madrid, Spain
Clínica Universidad de Navarra CUN
Pamplona, Spain
Instituto Valenciano de Oncología
Valencia, Spain
Time frame: At pre-dose, 0.5h, 1h, 2h, 3h, 6h, 8h, 22h, 46h, and 166h post-dose , beginning on day 1 of cycle 1
Cmax of total pegylated liposomal doxorubicin
Time frame: At pre-dose, 0.5h, 1h, 2h, 3h, 6h, 8h, 22h, 46h, and 166h post-dose, beginning on day 1 of cycle 1
Incidence of patients with CR, PR, SD or PD according to RECIST 1.1
CR (complete response) PR (partial response) SD (stable disease) PD (progressive disease)
Time frame: Up to 17 months or until discontinuation of study, whichever comes first
Incidence of positive anti-drug antibody titer
Time frame: Up to 17 months or until discontinuation of study, whichever comes first
Incidence of positive neutralizing antibody titer
Time frame: Up to 17 months or until discontinuation of study, whichever comes first