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Trial record 1 of 1 for:    NCT02696642
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Phase I Study of Anetumab Ravtansine in Hepatic or Renal Impairment

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ClinicalTrials.gov Identifier: NCT02696642
Recruitment Status : Completed
First Posted : March 2, 2016
Last Update Posted : September 4, 2019
Sponsor:
Information provided by (Responsible Party):
Bayer

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Neoplasms Drug: Anetumab ravtansine (BAY94-9343) Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : April 14, 2016
Actual Primary Completion Date : July 31, 2018
Actual Study Completion Date : August 19, 2019

Arm Intervention/treatment
Experimental: Anetumab ravtansine [hepatic control]
Subjects with adequate hepatic and renal function (controls)
Drug: Anetumab ravtansine (BAY94-9343)
All subjects will receive anetumab ravtansine 6.5 mg/kg BW (body weight) once every three weeks

Experimental: Anetumab ravtansine [mild impaired]
Subjects with mild hepatic impairment (Child-Pugh Class A and eGFR [estimated glomerular filtration rate] ≥60 mL/min/1.73 m2)
Drug: Anetumab ravtansine (BAY94-9343)
All subjects will receive anetumab ravtansine 6.5 mg/kg BW (body weight) once every three weeks

Experimental: Anetumab ravtansine [moderate impaired1]
Subjects with moderate hepatic impairment (Child-Pugh Class B and and eGFR ≥60 mL/min/1.73 m2)
Drug: Anetumab ravtansine (BAY94-9343)
All subjects will receive anetumab ravtansine 6.5 mg/kg BW (body weight) once every three weeks

Experimental: Anetumab ravtansine [moderate impaired2]
Moderate renal function impairment will be assessed by eGFR <60 and ≥30 mL/min per 1.73 m2
Drug: Anetumab ravtansine (BAY94-9343)
All subjects will receive anetumab ravtansine 6.5 mg/kg BW (body weight) once every three weeks




Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events (TEAEs, both serious and non-serious) or other abnormalities in safety assessments of BAY94-9343 [ Time Frame: Approximately 6 months per patient ]
  2. Cycle 1 AUC (area under the plasma concentration vs. time curve from zero to infinity after single (first) dose) of BAY94-9343 analytes [ Time Frame: At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 24h, 48h, 168h, 336h and 504h during cycle 1 ]
  3. Cycle 1 AUC(0-tlast) (AUC from time zero to the last data point > LLOQ [lower limit of quantification]) of BAY94-9343 analytes [ Time Frame: At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 24h, 48h, 168h, 336h and 504h during cycle 1 ]
  4. Cycle 1 Cmax (maximum drug concentration in plasma after the first dose administration) of BAY94-9343 analytes [ Time Frame: At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 24h, 48h, 168h, 336h and 504h during cycle 3 ]

Secondary Outcome Measures :
  1. Cycle 3 Cmax,md (Cmax after multiple-dose administration) of BAY94-9343 analytes [ Time Frame: At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 24h, 48h, 168h, 336h and 504h during cycle 3 ]
    Subjects will be eligible for the analysis of the secondary PK objective if they complete at least the first 3 treatment cycles (Cycle 1 to Cycle 3)

  2. Cycle 3 AUC(0-tlast)md (AUC(0-tlast) after multiple-dose administration) of BAY94-9343 analytes [ Time Frame: At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 24h, 48h, 168h, 336h and 504h during cycle 3 ]
    Subjects will be eligible for the analysis of the secondary PK objective if they complete at least the first 3 treatment cycles (Cycle 1 to Cycle 3)

  3. Immunogenicity as defined by the titer of anti-anetumab ravtansine antibodies (ADA) [ Time Frame: Approximately 6 months per patient ]
  4. Immunogenicity as defined by incidence of neutralizing antibodies (NA) [ Time Frame: Approximately 6 months per patient ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 m2 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02696642


Locations
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France
Caen, France, 14073
Dijon, France, 21000
Lille Cedex, France, 59020
Lyon Cedex, France, 69008
Marseille, France, 13915
Saint Herblain, France, 44805
Toulouse Cedex 9, France, 31059
Moldova, Republic of
Chisinau, Moldova, Republic of, 2025
Sponsors and Collaborators
Bayer
Investigators
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Study Director: Bayer Study Director Bayer

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Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02696642    
Other Study ID Numbers: 18327
2015-003897-33 ( EudraCT Number )
First Posted: March 2, 2016    Key Record Dates
Last Update Posted: September 4, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bayer:
mesothelin-expressing advanced solid cancers
Additional relevant MeSH terms:
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Renal Insufficiency
Kidney Diseases
Urologic Diseases
Maytansine
Immunoconjugates
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs