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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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ClinicalTrials.gov Identifier: NCT02751918
Recruitment Status : Completed
First Posted : April 26, 2016
Last Update Posted : November 22, 2019
Sponsor:
Information provided by (Responsible Party):
Bayer

Tracking Information
First Submitted Date  ICMJE April 22, 2016
First Posted Date  ICMJE April 26, 2016
Last Update Posted Date November 22, 2019
Actual Study Start Date  ICMJE June 8, 2016
Actual Primary Completion Date August 23, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 7, 2018)
  • Maximum tolerated dose (MTD) of Anetumab ravtansine in combination with pegylated liposomal doxorubicin when given every three weeks [ Time Frame: 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).
  • Incidence of serious and non-serious adverse events (AEs) [ Time Frame: Up to 6 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 22, 2016)
  • Maximum tolerated dose (MTD) of Anetumab ravtansine in combination with pegylated liposomal doxorubicin (at 30 mg/m2 of body surface area) when given every three weeks [ Time Frame: 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 (at 30 mg/m2 of body surface area) 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) [ Time Frame: Up to 6 months ]
Change History Complete list of historical versions of study NCT02751918 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 29, 2016)
  • 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 [ 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 [ Time Frame: Up to 17 months or until discontinuation of study, whichever comes first ]
    CR (complete response) PR (partial response) SD (stable disease) PD (progressive disease)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 22, 2016)
  • 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 [ 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 [ Time Frame: Up to 17 months or until discontinuation of study, whichever comes first ]
    CR (complete response) PR (partial response) SD (stable disease) PD (progressive disease)
  • Incidence of positive anti-drug antibody titer [ Time Frame: Up to 17 months or until discontinuation of study, whichever comes first ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase Ib Study of Anetumab Ravtansine in Combination With Pegylated Liposomal Doxorubicin in Patients With Recurrent Mesothelin-expressing Platinum-resistant Cancer
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ovarian Neoplasms
Intervention  ICMJE
  • Drug: Anetumab ravtansine (BAY94-9343)
    Anetumab ravtansine will be administered on Day 1 of every 21-day treatment cycle.
  • Drug: Pegylated Liposomal Doxorubicin
    Pegylated liposomal doxoribicin will be administered on Day 1 of every 21-day treatment cycle.
Study Arms  ICMJE Experimental: Anetumab ravtansine
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.
Interventions:
  • Drug: Anetumab ravtansine (BAY94-9343)
  • Drug: Pegylated Liposomal Doxorubicin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 26, 2019)
65
Original Estimated Enrollment  ICMJE
 (submitted: April 22, 2016)
40
Actual Study Completion Date  ICMJE October 31, 2019
Actual Primary Completion Date August 23, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Moldova, Republic of,   Spain,   United States
Removed Location Countries France,   Japan
 
Administrative Information
NCT Number  ICMJE NCT02751918
Other Study ID Numbers  ICMJE 18326
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bayer
Study Sponsor  ICMJE Bayer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bayer Study Director Bayer
PRS Account Bayer
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP