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.
- Conditions
- eoplasmata, maligne en niet-gespecificeerd: lokaal gevorderde of metastatische solide kankersoorten met mesotheline-expressie.Mesothelin-expressing advanced solid cancers
- Registration Number
- NL-OMON46366
- Lead Sponsor
- Bayer
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 8
- 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 or, in the investigator*s opinion, treatment in this study is clinically and ethically acceptable for the subject.;- Subjects must provide samples of archival tumor tissue collected and submitted anytime during the study.
- Subjects must have positive mesothelin expression in the archival tumor tissue, defined as the membrane intensity score of 1+, 2+ or 3+ (on the 0-3 scale) expressed on the membrane of >=5% of tumor cells combined.;- Life expectancy of at least 12 weeks.;- ECOG 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.;- Negative pregnancy test if woman of reproductive potential.;- If of reproductive potential, must agree to use adequate contraception as per protocol.
- 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 greater than or equal to 3 years before the start of anetumab ravtansine.;- New or progressive brain or meningeal or spinal metastases.;- Poor CYP2D6 metabolizers based on the screening test for CYP2D6 genetic polymorphisms.;- 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;- Left ventricular ejection fraction (LVEF) <50% at screening.;- Have QTc >450 ms or heart rate >=100 bpm or <=45 bpm at screening.;- Solid organ or bone marrow transplantation.;- Major surgery or significant trauma within 4 weeks before the start of anetumab ravtansine.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- ECG parameters (PR, QRS, QT/QTcF/QTcP interval duration, abnormal T and U<br /><br>waves, heart rate)<br /><br>- Cycle 1+2 AUC (area under the plasma concentration vs. time curve from zero<br /><br>to infinity after single (first) dose) of BAY94-9343 analytes<br /><br>- Cycle 1+2 AUC(0-tlast) (AUC from time zero to the last data point > LLOQ<br /><br>[lower limit of quantification]) of BAY94-9343 analytes<br /><br>- Cycle 1+2 Cmax (maximum drug concentration in plasma after the first dose<br /><br>administration) of BAY94-9343 analytes</p><br>
- Secondary Outcome Measures
Name Time Method <p>- Incidence of serious and non-serious adverse events<br /><br>- Incidence of positive anti-drug antibody titer<br /><br>- Cycle 3 Cmax,md (Cmax after multiple-dose administration) of BAY94-9343<br /><br>analytes<br /><br>- Cycle 3 AUC(0-tlast)md (AUC(0-tlast) after multiple-dose administration) of<br /><br>BAY94-9343 analytes<br /><br>- Incidence of neutralizing antibody titers</p><br>