- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02696642
Phase I Study of Anetumab Ravtansine in Hepatic or Renal Impairment
July 6, 2021 updated by: Bayer
An Open Label Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Immunogenicity of Anetumab Ravtansine in Subjects With Mesothelin-expressing Advanced Solid Cancers and Different Stages of Concurrent Hepatic or Renal Impairment
To characterize the safety, tolerability, pharmacokinetics and immunogenicity of anetumab ravtansine in subjects with advanced solid cancers and with different degrees of hepatic or renal impairment
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
54
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Caen, France, 14073
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Dijon, France, 21079
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Lille Cedex, France, 59020
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Lyon Cedex, France, 69008
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Marseille Cedex 5, France, 13385
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Saint Herblain, France, 44805
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Toulouse Cedex 9, France, 31059
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Chisinau, Moldova, Republic of, 2025
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Male or female subjects aged ≥18 years
- Histologically or cytologically confirmed, locally advanced or metastatic solid cancers known to express mesothelin on the tumor cell surface (e.g. predominantly epithelial [>=50% tumor component] pleural or peritoneal mesothelioma, epithelial ovarian cancer [including the fallopian tube or primary peritoneal], adenocarcinoma of the pancreas, triple-negative adenocarcinoma of the breast, non-small-cell adenocarcinoma of the lung, endometrial cancer, serous uterine cancer, gastric cancer [including the gastro-esophageal junction], colon cancer, cholangiocarcinoma, thymic carcinoma, etc.). Subjects with resected primary cancers who have documented metastases or local recurrence are eligible.
- Subjects must have no standard therapy available, or have actively refused standard therapy
Subjects must meet the criteria for one of the 4 treatment groups:
- Group A: Adequate hepatic and renal function (controls)
- Group B: Mild hepatic impairment, i.e. Grade A according to the Child-Pugh Classification (total score of 5 or 6) and adequate renal function
- Group C: Moderate hepatic impairment, i.e. Grade B according to the Child-Pugh Classification (total score of 7, 8 or 9) and adequate renal function
- Group D: Moderate renal impairment, i.e. eGFR (estimated glomerular filtration rate) <60 and ≥30 mL/min per 1.73 m*2 and hepatic function better than, or equal to mild impairment according to the Child-Pugh Classification (total score ≤6)
- Adequate bone marrow function
- Life expectancy of at least 12 weeks
- ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1 (control and mild hepatic impairment groups), or 0-2 (moderate hepatic impairment and moderate renal impairment groups)
Exclusion Criteria:
- Subjects who have a previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study, except cervical carcinoma in situ, treated basal cell carcinoma, superficial noninvasive bladder tumors or any previous cancer curatively treated >3 years before the start of anetumab ravtansine
- Subjects who have new or progressive brain or meningeal or spinal metastases
- Subjects who have Gilbert's syndrome or other benign congenital hyperbilirubinemia are not eligible for the mild or moderate hepatic impairment or moderate renal impairment groups.
- Subjects who have a history or current evidence of bleeding disorder, i.e. any hemorrhage/bleeding event of CTCAE (Common Terminology Criteria for Adverse Events) Grade ≥2 bleeding within 4 weeks before the start of anetumab ravtansine
- Subjects who have a history or current evidence of uncontrolled cardiovascular disease or hypertension.
- Fridericia-corrected QT interval (QTcF) >480 ms, heart rate ≥100 beats per minute (bpm) or ≤45 bpm, LVEF (left ventricular ejection fraction) <50%
- Subjects with corneal epitheliopathy or any eye disorder that may predispose the subjects to drug-induced corneal epitheliopathy or may interfere with diagnosis of treatment-emergent corneal epitheliopathy at the investigator's discretion in consultation with an ophthalmologist.
- Subjects who have received systemic anticancer therapy (except pemetrexed, cisplatin, carboplatin and topical or intracavitary treatments with negligible absorption in systemic circulation ) within 4 weeks before the start of anetumab ravtansine, or within 5 half-lives of the anticancer agent before the start of anetumab ravtansine, whichever is longer. Mitomycin C or nitrosoureas must be excluded within 6 weeks before the start of anetumab ravtansine.
- Subjects who have received radiotherapy within 4 weeks before the start of anetumab ravtansine
- Use of drugs that, in the opinion of the investigator, have a strong potential for renal or hepatic toxicity within 2 weeks before the start of anetumab ravtansine until the EoT visit.
- Use of strong cytochrome P450 3A4 (CYP3A4) inhibitors or strong CYP3A4 inducers within 2 weeks before the start of anetumab ravtansine until the EoT visit
- Women who are pregnant or breast-feeding
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Control group
Anetumab ravtansine was given at 6.5 mg/kg body weight (BW) as a 1 hour intravenous (IV) infusion once every 3 weeks (Q3W) for subjects with adequate hepatic and renal function.
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All subjects received anetumab ravtansine 6.5 mg/kg BW (body weight) once every three weeks
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Experimental: mild HI group
Anetumab ravtansine was given at 6.5 mg/kg BW as a 1 hour IV infusion Q3W for subjects with mild hepatic impairment (HI).
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All subjects received anetumab ravtansine 6.5 mg/kg BW (body weight) once every three weeks
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Experimental: moderate HI group
Anetumab ravtansine was given at 6.5 mg/kg BW as a 1 hour IV infusion Q3W for subjects with moderate hepatic impairment (HI).
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All subjects received anetumab ravtansine 6.5 mg/kg BW (body weight) once every three weeks
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Experimental: moderate RI group
Anetumab ravtansine was given at 6.5 mg/kg BW as a 1 hour IV infusion Q3W for subjects with moderate renal impairment (RI).
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All subjects received anetumab ravtansine 6.5 mg/kg BW (body weight) once every three weeks
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Number of subjects with treatment-emergent adverse events (TEAEs) and significant abnormalities in safety assessments related to anetumab ravtansine (BAY94-9343) in each of the 4 treatment groups
Time Frame: After the first application of the study drug up until the safety follow up visit, i.e., 30-35 days after the last dose of the study drug.
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After the first application of the study drug up until the safety follow up visit, i.e., 30-35 days after the last dose of the study drug.
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AUC for antibody drug conjugate (ADC), total antibody (TA), derivative 4 of maytansine (DM4), and S methyl derivate of DM4 (DM4-Me) after single (first) dose administration of anetumab ravtansine (BAY94-9343) in Cycle 1
Time Frame: From pre-dose until 504 hours post dose during cycle 1
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From pre-dose until 504 hours post dose during cycle 1
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AUC(0-tlast) for ADC, TA, DM4 and DM4-Me after single (first) dose administration of anetumab ravtansine (BAY94-9343) in Cycle 1
Time Frame: From pre-dose until 504 hours post dose during cycle 1
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From pre-dose until 504 hours post dose during cycle 1
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Cmax for ADC, TA, DM4 and DM4-Me after single (first) dose administration of anetumab ravtansine (BAY94-9343) in Cycle 1
Time Frame: From pre-dose until 504 hours post dose during cycle 1
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From pre-dose until 504 hours post dose during cycle 1
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Cmax,md for ADC, TA, DM4 and DM4-Me in Cycle 3
Time Frame: From pre-dose until 504 hours post dose during cycle 3
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From pre-dose until 504 hours post dose during cycle 3
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AUC(0-tlast)md for ADC, TA, DM4 and DM4-Me in Cycle 3
Time Frame: From pre-dose until 504 hours post dose during cycle 3
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From pre-dose until 504 hours post dose during cycle 3
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Number of subjects with positive immunogenicity results for anti anetumab ravtansine (BAY94-9343) antibodies (anti drug antibody [ADA])
Time Frame: From pre-dose on Day1 of Cycle 1 until the safety follow-up visit, i.e., 30-35 days after the last dose of the study drug
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From pre-dose on Day1 of Cycle 1 until the safety follow-up visit, i.e., 30-35 days after the last dose of the study drug
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Number of subjects with positive immunogenicity results for anetumab ravtansine (BAY94-9343) neutralizing antibody (NAB)
Time Frame: From pre-dose on Day1 of Cycle 1 until the safety follow-up visit, i.e., 30-35 days after the last dose of the study drug
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From pre-dose on Day1 of Cycle 1 until the safety follow-up visit, i.e., 30-35 days after the last dose of the study drug
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 14, 2016
Primary Completion (Actual)
July 31, 2018
Study Completion (Actual)
August 19, 2019
Study Registration Dates
First Submitted
February 26, 2016
First Submitted That Met QC Criteria
February 26, 2016
First Posted (Estimate)
March 2, 2016
Study Record Updates
Last Update Posted (Actual)
July 9, 2021
Last Update Submitted That Met QC Criteria
July 6, 2021
Last Verified
July 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 18327 (Other Identifier: City of Hope Comprehensive Cancer Center)
- 2015-003897-33 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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