Clinical trial NCT02751918: Phase Ib Study of Anetumab Ravtansine in Combination With Pegylated Liposomal Doxorubicin in Patients With Recurrent Mesothelin-expressing Platinum-resistant Cancer
Official title: An Open-label Phase Ib Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Maximum Tolerated Dose of Anetumab Ravtansine in Combination With Pegylated Liposomal Doxorubicin 30 mg/m2 Given Every 3 Weeks in Subjects With Mesothelin-expressing Platinum-resistant Recurrent Ovarian, Fallopian Tube or Primary Peritoneal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ovarian Neoplasms
Keywords: Mesothelin-expressing platinum-resistant cancer
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2016-04-26
Enrollment: 65
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Subjects with locally invasive or metastatic, epithelial ovarian, fallopian tube, or primary peritoneal cancer
* Subjects must provide samples of tumor tissue
* Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

* Subjects with low-grade ovarian, fallopian tube, or Primary peritoneal cancer
* Women who are pregnant or breast feeding
* Subjects who have an active hepatitis B virus or hepatitis C virus infection requiring treatment as defined in the protocol

Primary outcomes:
measure: Maximum tolerated dose (MTD) of Anetumab ravtansine in combination with pegylated liposomal doxorubicin when given every three weeks
timeFrame: Up to 6 months, minimum: 1 cycle (=21days)
measure: Incidence of serious and non-serious adverse events (AEs)
timeFrame: Up to 6 months
Secondary outcomes:
measure: 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)
timeFrame: 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
measure: 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)
timeFrame: 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
measure: Cmax (maximum drug concentration in plasma after first dose administration) of Anetumab ravtansine analytes (Antibody drug conjugates, Total Antibody, metabolites DM4, and DM4-Me)
timeFrame: 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
measure: AUC of total pegylated liposomal doxorubicin
timeFrame: At pre-dose, 0.5h, 1h, 2h, 3h, 6h, 8h, 22h, 46h, and 166h post-dose , beginning on day 1 of cycle 1
measure: AUC(0-tlast) of total pegylated liposomal doxorubicin
timeFrame: At pre-dose, 0.5h, 1h, 2h, 3h, 6h, 8h, 22h, 46h, and 166h post-dose , beginning on day 1 of cycle 1
measure: Cmax of total pegylated liposomal doxorubicin
timeFrame: At pre-dose, 0.5h, 1h, 2h, 3h, 6h, 8h, 22h, 46h, and 166h post-dose, beginning on day 1 of cycle 1
measure: Incidence of patients with CR, PR, SD or PD according to RECIST 1.1
timeFrame: Up to 17 months or until discontinuation of study, whichever comes first
measure: Incidence of positive anti-drug antibody titer
timeFrame: Up to 17 months or until discontinuation of study, whichever comes first
measure: Incidence of positive neutralizing antibody titer
timeFrame: Up to 17 months or until discontinuation of study, whichever comes first
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Oklahoma City
country: United States
facility: Oklahoma University Health Science Center
state: Oklahoma
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Chisinau
country: Moldova, Republic of
facility: The Institute of Oncology
city: Barcelona
country: Spain
facility: Ciutat Sanitària i Universitaria de la Vall d'Hebron
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra CUN en Madrid
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra CUN
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: