check_circleStudy Completed

Medical Oncology

Thorough ECG (electrocardiogram) and drug interaction study with anetumab ravtansine and itraconazole

Trial purpose

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

Key Participants Requirements

Sex

Both

Age

18 - N/A
  • - Subjects must have histologically confirmed, locally advanced or metastatic solid cancers of the following histological types:
    a.) predominantly epithelial (≥50% tumor component) pleural or peritoneal mesothelioma
    b.) epithelial ovarian cancer (fallopian tube and primary peritoneal cancers are eligible)
    c.) adenocarcinoma of the pancreas,
    d.) triple-negative adenocarcinoma of the breast
    e.) non-small-cell adenocarcinoma of the lung
    f.) gastric cancer (including gastro-esophageal junction)
    g.) colon cancer
    h.) cholangiocarcinoma
    i.) Thymic carcinoma
    - Subjects must have no standard therapy available, or have actively refused standard therapy
    - Subjects must provide samples of archival tumor tissue collected and submitted anytime during the study
    - Subjects must have a life expectancy of at least 12 weeks
    - Subjects must have ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1
    - Subjects must have adequate bone marrow, renal and hepatic function and coagulation
    - Subjects must have normal or clinically insignificant ECG at screening
    - Women of reproductive potential must have a negative serum pregnancy test obtained within 3 days before the start of anetumab ravtansine
    - 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.
  • - 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
    - New or progressive brain or meningeal or spinal metastases
    - 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
    - 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
    - Had a major surgery or significant trauma within 4 weeks before the start of anetumab ravtansine
    - Had solid organ or bone marrow transplantation
    - Have LVEF (left ventricular ejection fraction) <50% at screening
    - Have QTc >450 ms or heart rate ≥100 bpm or ≤45 bpm at screening
    - Poor CYP2D6 metabolizers based on the screening test for genetic polymorphisms in CYP2D6 metabolizing capacity

Trial summary

Enrollment Goal
63
Trial Dates
September 2016 - August 2019
Phase
Phase 1
Could I Receive a placebo
No
Products
Anetumab ravtansine (BAY94-9343)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
UCLA-Santa Monica Medical CenterSanta Monica, 90404, United States
Completed
University Hospitals Cleveland Medical CenterCleveland, 44106, United States
Completed
Henry Ford Health SystemDetroit, 48202, United States
Completed
Washington University School of MedicineSt. Louis, 63110, United States
Completed
Mary Crowley Medical Research CenterDallas, 75230, United States
Completed
Epworth HealthCareRichmond, 3122, Australia
Completed
Blacktown Cancer & Haematology CentreBlacktown, 2148, Australia
Completed
Ciutat Sanitària i Universitaria de la Vall d'HebronBarcelona, 08035, Spain
Completed
Fundacion Jimenez Diaz (Clinica de la Concepcion)Madrid, 28040, Spain
Completed
Hospital Virgen de la VictoriaMálaga, 29010, Spain
Completed
Centre Georges Francois Leclerc DijonDIJON, 21079, France
Completed
Hôpital Henri MondorCRETEIL, 94010, France
Completed
Hôpital de la Timone - MarseilleMARSEILLE, 13005, France
Completed
CU Saint-Luc/UZ St-LucBRUXELLES - BRUSSEL, 1200, Belgium
Completed
UZ GentGENT, 9000, Belgium
Withdrawn
UZ Leuven GasthuisbergLEUVEN, 3000, Belgium
Completed
Universitair Medisch Centrum St. RadboudNIJMEGEN, 6525 GA, Netherlands
Withdrawn
University College HospitalLondon, NW1 2BU, United Kingdom
Completed
Nederlands Kanker InstituutAMSTERDAM, 1066 CX, Netherlands
Completed
VUmcAMSTERDAM, 1081 HV, Netherlands
Withdrawn
Ochsner Medical Center - New OrleansNew Orleans, 70121-2429, United States
Withdrawn
Dartmouth Hitchock Medical CenterLebanon, 03756, United States
Withdrawn
Univ.of California-San Diego Moores Cancer CenterLa Jolla, 92093-1503, United States

Primary Outcome

  • PR interval duration
    ECG evaluation
    date_rangeTime Frame:
    Up to 2 months per patient
    enhanced_encryption
    Safety Issue:
    Yes
  • QRS interval duration
    ECG evaluation
    date_rangeTime Frame:
    Up to 2 months per patient
    enhanced_encryption
    Safety Issue:
    Yes
  • QT interval duration
    ECG evaluation
    date_rangeTime Frame:
    Up to 2 months per patient
    enhanced_encryption
    Safety Issue:
    Yes
  • Abnormal T/U waves
    ECG evaluation
    date_rangeTime Frame:
    Up to 2 months per patient
    enhanced_encryption
    Safety Issue:
    Yes
  • Heart rate
    ECG evaluation
    date_rangeTime Frame:
    Up to 2 months per patient
    enhanced_encryption
    Safety Issue:
    Yes
  • Cycle 1+2 AUC (area under the plasma concentration vs. time curve from zero to infinity after single (first) dose) of BAY94-9343 analytes
    date_rangeTime Frame:
    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
    enhanced_encryption
    Safety Issue:
    No
  • Cycle 1+2 AUC(0-tlast) (AUC from time zero to the last data point > LLOQ [lower limit of quantification]) of BAY94-9343 analytes
    date_rangeTime Frame:
    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
    enhanced_encryption
    Safety Issue:
    No
  • Cycle 1+2 Cmax (maximum drug concentration in plasma after the first dose administration) of BAY94-9343 analytes
    date_rangeTime Frame:
    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
    enhanced_encryption
    Safety Issue:
    No
  • QTcF (QT interval, corrected for heart rate according to Fridericia's formula) interval duration
    ECG evaluation
    date_rangeTime Frame:
    Up to 2 months per patient
    enhanced_encryption
    Safety Issue:
    Yes
  • QTcP (QT interval, corrected for heart rate using a population-specific correction) interval duration
    ECG evaluation
    date_rangeTime Frame:
    Up to 2 months per patient
    enhanced_encryption
    Safety Issue:
    Yes

Secondary Outcome

  • Incidence of serious adverse events
    date_rangeTime Frame:
    Up to 6 months per patient
    enhanced_encryption
    Safety Issue:
    Yes
  • Incidence of non-serious adverse events
    date_rangeTime Frame:
    Up to 6 months per patient
    enhanced_encryption
    Safety Issue:
    Yes
  • Incidence of positive anti-drug antibody titer
    date_rangeTime Frame:
    Up to 6 months per patient
    enhanced_encryption
    Safety Issue:
    No
  • Incidence of neutralizing antibody titers
    date_rangeTime Frame:
    Up to 6 months per patient
    enhanced_encryption
    Safety Issue:
    No
  • Cycle 3 Cmax,md (Cmax after multiple-dose administration) of BAY94-9343 analytes
    date_rangeTime Frame:
    At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 168h, 336h and 504h between 43rd and 64th days of the study
    enhanced_encryption
    Safety Issue:
    No
  • Cycle 3 AUC(0-tlast)md (AUC(0-tlast) after multiple-dose administration) of BAY94-9343 analytes
    date_rangeTime Frame:
    At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 168h, 336h and 504h between 43rd and 64th days of the study
    enhanced_encryption
    Safety Issue:
    No

Trial design

An open label, Phase I study to assess the effect of itraconazole (CYP3A4 and P-gp inhibitor) on the pharmacokinetics of anetumab ravtansine and to assess the ECG effects, safety and immunogenicity of anetumab ravtansine given as a single agent and together with itraconazole in subjects with mesothelin-expressing advanced solid cancers
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
N/A
Blinding
Open Label
Assignment
Single Group Assignment
Trial Arms
1