Thorough ECG (Electrocardiogram) and Drug Interaction Study With Anetumab Ravtansine and Itraconazole
- Conditions
- Medical Oncology
- Interventions
- Drug: Anetumab ravtansine (BAY94-9343)
- Registration Number
- NCT02824042
- Lead Sponsor
- Bayer
- Brief Summary
Characterize the safety, tolerability, ECG effects, pharmacokinetics and immunogenicity of anetumab ravtansine given as single agent and after inhibition of CYP3A4 and P-gp by concomitant administration of itraconazole in subjects with mesothelin-expressing advanced solid cancers
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 63
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Subjects must have histologically confirmed, locally advanced or metastatic solid cancers of the following histological types:
- predominantly epithelial (≥50% tumor component) pleural or peritoneal mesothelioma
- epithelial ovarian cancer (fallopian tube and primary peritoneal cancers are eligible)
- adenocarcinoma of the pancreas,
- triple-negative adenocarcinoma of the breast
- non-small-cell adenocarcinoma of the lung
- gastric cancer (including gastro-esophageal junction)
- colon cancer
- cholangiocarcinoma
- Thymic carcinoma
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Subjects must have no standard therapy available, or have actively refused standard therapy
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Subjects must provide samples of archival tumor tissue collected and submitted anytime during the study
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Subjects must have a life expectancy of at least 12 weeks
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Subjects must have ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1
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Subjects must have adequate bone marrow, renal and hepatic function and coagulation
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Subjects must have normal or clinically insignificant ECG at screening
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Women of reproductive potential must have a negative serum pregnancy test obtained within 3 days before the start of anetumab ravtansine
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Women of childbearing potential and fertile men must agree to use adequate contraception when sexually active. This applies from the time period between signing of the informed consent until at least 6 months after the last administration of the last study drug. Male patients with a female partner of childbearing potential must use a condom and ensure that an additional form of contraception is also used during treatment and until 6 months after last study drug administration.
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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
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New or progressive brain or meningeal or spinal metastases
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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 ophthalmologist's or the investigator's discretion
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History or current evidence of
- biliary cirrhosis
- malignant biliary obstruction unless the bile flow to the gastrointestinal tract is maintained by a fully operational biliary stent
- CTCAE (Common Terminology Criteria for Adverse Events) Grade ≥2 bleeding disorder within 4 weeks before the start of anetumab ravtansine
- uncontrolled cardiovascular disease or uncontrolled hypertension
- Long QT Syndrome
- HIV infection
- Hepatitis B or C infection
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Had a major surgery or significant trauma within 4 weeks before the start of anetumab ravtansine
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Had solid organ or bone marrow transplantation
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Have LVEF (left ventricular ejection fraction) <50% at screening
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Have QTc >450 ms or heart rate ≥100 bpm or ≤45 bpm at screening
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Poor CYP2D6 metabolizers based on the screening test for genetic polymorphisms in CYP2D6 metabolizing capacity
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Anetumab ravtansine Anetumab ravtansine (BAY94-9343) The evaluation of multiple ECG parameters and the drug-drug interaction (DDI) potential of anetumab ravtansine parameters when administered alone and together with itraconazole 100 mg oral capsules will be conducted in 2 sequential parts. On Cycle 1 Day 1, anetumab ravtansine will be given alone at a dose of 6.5 mg/kg in Part 1 and Part 2. On Cycle 2 Day 1, anetumab ravtansine will be given together with itraconazole at a dose of 0.6 mg/kg in Part 1, and at a dose of 6.5 mg/kg (planned) in Part 2. Anetumab ravtansine Itraconazole The evaluation of multiple ECG parameters and the drug-drug interaction (DDI) potential of anetumab ravtansine parameters when administered alone and together with itraconazole 100 mg oral capsules will be conducted in 2 sequential parts. On Cycle 1 Day 1, anetumab ravtansine will be given alone at a dose of 6.5 mg/kg in Part 1 and Part 2. On Cycle 2 Day 1, anetumab ravtansine will be given together with itraconazole at a dose of 0.6 mg/kg in Part 1, and at a dose of 6.5 mg/kg (planned) in Part 2.
- Primary Outcome Measures
Name Time Method PR interval duration Up to 2 months per patient ECG evaluation
QT interval duration Up to 2 months per patient ECG evaluation
Cycle 1+2 AUC (area under the plasma concentration vs. time curve from zero to infinity after single (first) dose) of BAY94-9343 analytes At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 10h, 24h, 48h, 168h, 336h, 480h and 504h after each dose during first 42 days of the study Cycle 1+2 Cmax (maximum drug concentration in plasma after the first dose administration) of BAY94-9343 analytes At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 10h, 24h, 48h, 168h, 336h, 480h and 504h after each dose during first 42 days of the study QTcF (QT interval, corrected for heart rate according to Fridericia's formula) interval duration Up to 2 months per patient ECG evaluation
Cycle 1+2 AUC(0-tlast) (AUC from time zero to the last data point > LLOQ [lower limit of quantification]) of BAY94-9343 analytes At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 10h, 24h, 48h, 168h, 336h, 480h and 504h after each dose during first 42 days of the study Abnormal T/U waves Up to 2 months per patient ECG evaluation
QRS interval duration Up to 2 months per patient ECG evaluation
Heart rate Up to 2 months per patient ECG evaluation
QTcP (QT interval, corrected for heart rate using a population-specific correction) interval duration Up to 2 months per patient ECG evaluation
- Secondary Outcome Measures
Name Time Method Incidence of non-serious adverse events Up to 6 months per patient Incidence of serious adverse events Up to 6 months per patient Incidence of positive anti-drug antibody titer Up to 6 months per patient Cycle 3 Cmax,md (Cmax after multiple-dose administration) of BAY94-9343 analytes At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 168h, 336h and 504h between 43rd and 64th days of the study Cycle 3 AUC(0-tlast)md (AUC(0-tlast) after multiple-dose administration) of BAY94-9343 analytes At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 168h, 336h and 504h between 43rd and 64th days of the study Incidence of neutralizing antibody titers Up to 6 months per patient
Trial Locations
- Locations (18)
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Blacktown Cancer & Haematology Centre
🇦🇺Blacktown, New South Wales, Australia
Centre Georges Francois Leclerc Dijon
🇫🇷Dijon, France
Hôpital de la Timone - Marseille
🇫🇷Marseille, France
Hôpital Henri Mondor
🇫🇷Creteil, France
Fundacion Jimenez Diaz (Clinica de la Concepcion)
🇪🇸Madrid, Spain
Ciutat Sanitària i Universitaria de la Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Virgen de la Victoria
🇪🇸Málaga, Spain
UCLA-Santa Monica Medical Center
🇺🇸Santa Monica, California, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Mary Crowley Medical Research Center
🇺🇸Dallas, Texas, United States
Epworth HealthCare
🇦🇺Richmond, Victoria, Australia
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
CU Saint-Luc/UZ St-Luc
🇧🇪Bruxelles - Brussel, Belgium
UZ Gent
🇧🇪Gent, Belgium
Nederlands Kanker Instituut
🇳🇱Amsterdam, Netherlands
VUmc
🇳🇱Amsterdam, Netherlands
Universitair Medisch Centrum St. Radboud
🇳🇱Nijmegen, Netherlands