Phase Ib Study of Anetumab Ravtansine in Combination With Pegylated Liposomal Doxorubicin in Patients With Recurrent Mesothelin-expressing Platinum-resistant Cancer
Primary Purpose
Ovarian Neoplasms
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Anetumab ravtansine (BAY94-9343)
Pegylated Liposomal Doxorubicin
Sponsored by
About this trial
This is an interventional treatment trial for Ovarian Neoplasms focused on measuring Mesothelin-expressing platinum-resistant cancer
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
Sites / Locations
- Rocky Mountain Cancer Centers
- Yale University School of Medicine
- Oklahoma University Health Science Center
- UZ Leuven Gasthuisberg
- The Institute of Oncology
- Ciutat Sanitària i Universitaria de la Vall d'Hebron
- Clinica Universidad de Navarra CUN en Madrid
- Clínica Universidad de Navarra CUN
- Instituto Valenciano de Oncología
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Anetumab ravtansine
Arm Description
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.
Outcomes
Primary Outcome Measures
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).
Incidence of serious and non-serious adverse events (AEs)
Secondary Outcome Measures
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)
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)
Cmax (maximum drug concentration in plasma after first dose administration) of Anetumab ravtansine analytes (Antibody drug conjugates, Total Antibody, metabolites DM4, and DM4-Me)
AUC of total pegylated liposomal doxorubicin
AUC(0-tlast) of total pegylated liposomal doxorubicin
Cmax of total pegylated liposomal doxorubicin
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)
Incidence of positive anti-drug antibody titer
Incidence of positive neutralizing antibody titer
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02751918
Brief Title
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
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
June 8, 2016 (Actual)
Primary Completion Date
August 23, 2019 (Actual)
Study Completion Date
October 31, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Neoplasms
Keywords
Mesothelin-expressing platinum-resistant cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
65 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Anetumab ravtansine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Anetumab ravtansine (BAY94-9343)
Intervention Description
Anetumab ravtansine will be administered on Day 1 of every 21-day treatment cycle.
Intervention Type
Drug
Intervention Name(s)
Pegylated Liposomal Doxorubicin
Intervention Description
Pegylated liposomal doxoribicin will be administered on Day 1 of every 21-day treatment cycle.
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD) of Anetumab ravtansine in combination with pegylated liposomal doxorubicin when given every three weeks
Description
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)
Title
Incidence of serious and non-serious adverse events (AEs)
Time Frame
Up to 6 months
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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
Title
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
Title
AUC(0-tlast) 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
Title
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
Title
Incidence of patients with CR, PR, SD or PD according to RECIST 1.1
Description
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
Title
Incidence of positive anti-drug antibody titer
Time Frame
Up to 17 months or until discontinuation of study, whichever comes first
Title
Incidence of positive neutralizing antibody titer
Time Frame
Up to 17 months or until discontinuation of study, whichever comes first
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
Facility Name
Rocky Mountain Cancer Centers
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80012
Country
United States
Facility Name
Yale University School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520-8064
Country
United States
Facility Name
Oklahoma University Health Science Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
UZ Leuven Gasthuisberg
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
The Institute of Oncology
City
Chisinau
ZIP/Postal Code
2025
Country
Moldova, Republic of
Facility Name
Ciutat Sanitària i Universitaria de la Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Clinica Universidad de Navarra CUN en Madrid
City
Madrid
ZIP/Postal Code
28027
Country
Spain
Facility Name
Clínica Universidad de Navarra CUN
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
Facility Name
Instituto Valenciano de Oncología
City
Valencia
ZIP/Postal Code
46009
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
Phase Ib Study of Anetumab Ravtansine in Combination With Pegylated Liposomal Doxorubicin in Patients With Recurrent Mesothelin-expressing Platinum-resistant Cancer
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