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

Ovarian Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02751918
• Other study ID #: 18326
• Status: Completed
• Phase: Phase 1
• Start date: June 8, 2016
• Est. completion date: October 31, 2019

Study information

• Verified date: November 2019
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: October 31, 2019
• Est. primary completion date: August 23, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Ovarian Neoplasms

Intervention

Drug:
• Anetumab ravtansine (BAY94-9343)
Anetumab ravtansine will be administered on Day 1 of every 21-day treatment cycle.
• Pegylated Liposomal Doxorubicin
Pegylated liposomal doxoribicin will be administered on Day 1 of every 21-day treatment cycle.

Locations

Country	Name	City	State
Belgium	UZ Leuven Gasthuisberg	Leuven
Moldova, Republic of	The Institute of Oncology	Chisinau
Spain	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
United States	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

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Belgium,  Moldova, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Up to 6 months, minimum: 1 cycle (=21days)
Primary	Incidence of serious and non-serious adverse events (AEs)		Up to 6 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)	Up to 17 months or until discontinuation of study, whichever comes first
Secondary	Incidence of positive anti-drug antibody titer		Up to 17 months or until discontinuation of study, whichever comes first
Secondary	Incidence of positive neutralizing antibody titer		Up to 17 months or until discontinuation of study, whichever comes first