Phase Ib Study of Anetumab Ravtansine in Combination With Pegylated Liposomal Doxorubicin in Patients With Recurrent Mesothelin-expressing Platinum-resistant Cancer

Phase 1

Completed

• Conditions: Ovarian Neoplasms
• Interventions: Drug: Anetumab ravtansine (BAY94-9343); Drug: Pegylated Liposomal Doxorubicin

• Registration Number: NCT02751918
• Lead Sponsor: Bayer

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-04-22
• Study First Submitted QC: 2016-04-22
• Study First Posted: 2016-04-26
• Study Start: 2016-06-08
• Primary Completion: 2019-08-23
• Study Completion: 2019-10-31
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-21
• Last Update Posted: 2019-11-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 65

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Anetumab ravtansine	Pegylated Liposomal Doxorubicin	Anetumab ravtansine in combination with pegylated liposomal doxorubicin in subjects with mesothelin-expressing platinum-resistant recurrent ovarian, fallopian tube, or primary peritoneal cancer. Increase/Decrease of Anetumab ravtansine until maximum tolerated dose identified.
Anetumab ravtansine	Anetumab ravtansine (BAY94-9343)	Anetumab ravtansine in combination with pegylated liposomal doxorubicin in subjects with mesothelin-expressing platinum-resistant recurrent ovarian, fallopian tube, or primary peritoneal cancer. Increase/Decrease of Anetumab ravtansine until maximum tolerated dose identified.

Primary Outcome Measures

Name	Time	Method
Incidence of serious and non-serious adverse events (AEs)	Up to 6 months
Maximum tolerated dose (MTD) of Anetumab ravtansine in combination with pegylated liposomal doxorubicin when given every three weeks	Up to 6 months, minimum: 1 cycle (=21days)	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).

Secondary Outcome Measures

Name	Time	Method
Cmax of total pegylated liposomal doxorubicin	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	Up to 17 months or until discontinuation of study, whichever comes first	CR (complete response) PR (partial response) SD (stable disease) PD (progressive disease)
Cmax (maximum drug concentration in plasma after first dose administration) of Anetumab ravtansine analytes (Antibody drug conjugates, Total Antibody, metabolites DM4, and DM4-Me)	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 (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)	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	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 positive neutralizing antibody titer	Up to 17 months or until discontinuation of study, whichever comes first
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)	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) of total pegylated liposomal doxorubicin	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 positive anti-drug antibody titer	Up to 17 months or until discontinuation of study, whichever comes first

Trial Locations

Locations (9)

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; 🇧🇪 Leuven, Belgium

The Institute of Oncology; 🇲🇩 Chisinau, Moldova, Republic of

Ciutat Sanitària i Universitaria de la Vall d'Hebron; 🇪🇸 Barcelona, Spain

Clínica Universidad de Navarra CUN; 🇪🇸 Pamplona, Spain

Instituto Valenciano de Oncología; 🇪🇸 Valencia, Spain

Clinica Universidad de Navarra CUN en Madrid; 🇪🇸 Madrid, Spain