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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02824042




Registration number
NCT02824042
Ethics application status
Date submitted
27/06/2016
Date registered
6/07/2016

Titles & IDs
Public title
Thorough ECG (Electrocardiogram) and Drug Interaction Study With Anetumab Ravtansine and Itraconazole
Scientific title
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
Secondary ID [1] 0 0
2017-001978-42
Secondary ID [2] 0 0
18329
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Medical Oncology 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Anetumab ravtansine (BAY94-9343)
Treatment: Drugs - Itraconazole

Experimental: Anetumab ravtansine - 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.


Treatment: Drugs: Anetumab ravtansine (BAY94-9343)
Anetumab ravtansine given IV On Day 1 of each 21-day treatment cycle Part 1: Cycle 1 Day 1: 6.5 mg/kg of body weight (BW) Cycle 2 Day 1: 0.6 mg/kg BW Part 2: Cycle 1 Day 1: 6.5 mg/kg BW Cycle 2 Day 1: 6.5 mg/kg BW (planned dose) Continuous treatment: Cycles =3 Day 1: 6.5 mg/kg BW once every 3 weeks (Q3W)

Treatment: Drugs: Itraconazole
Itraconazole 100 mg oral capsules given by mouth Cycle 1 (Day 18): 200 mg twice daily (BID) (Days 19 - 21): 200 mg once daily (QD) Cycle 2 (Days 1-8): 200 mg QD 12 days in total (Part 1 or Part 2)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
PR interval duration
Timepoint [1] 0 0
Up to 2 months per patient
Primary outcome [2] 0 0
QRS interval duration
Timepoint [2] 0 0
Up to 2 months per patient
Primary outcome [3] 0 0
QT interval duration
Timepoint [3] 0 0
Up to 2 months per patient
Primary outcome [4] 0 0
Abnormal T/U waves
Timepoint [4] 0 0
Up to 2 months per patient
Primary outcome [5] 0 0
Heart rate
Timepoint [5] 0 0
Up to 2 months per patient
Primary outcome [6] 0 0
Cycle 1+2 AUC (area under the plasma concentration vs. time curve from zero to infinity after single (first) dose) of BAY94-9343 analytes
Timepoint [6] 0 0
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
Primary outcome [7] 0 0
Cycle 1+2 AUC(0-tlast) (AUC from time zero to the last data point > LLOQ [lower limit of quantification]) of BAY94-9343 analytes
Timepoint [7] 0 0
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
Primary outcome [8] 0 0
Cycle 1+2 Cmax (maximum drug concentration in plasma after the first dose administration) of BAY94-9343 analytes
Timepoint [8] 0 0
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
Primary outcome [9] 0 0
QTcF (QT interval, corrected for heart rate according to Fridericia's formula) interval duration
Timepoint [9] 0 0
Up to 2 months per patient
Primary outcome [10] 0 0
QTcP (QT interval, corrected for heart rate using a population-specific correction) interval duration
Timepoint [10] 0 0
Up to 2 months per patient
Secondary outcome [1] 0 0
Incidence of serious adverse events
Timepoint [1] 0 0
Up to 6 months per patient
Secondary outcome [2] 0 0
Incidence of non-serious adverse events
Timepoint [2] 0 0
Up to 6 months per patient
Secondary outcome [3] 0 0
Incidence of positive anti-drug antibody titer
Timepoint [3] 0 0
Up to 6 months per patient
Secondary outcome [4] 0 0
Incidence of neutralizing antibody titers
Timepoint [4] 0 0
Up to 6 months per patient
Secondary outcome [5] 0 0
Cycle 3 Cmax,md (Cmax after multiple-dose administration) of BAY94-9343 analytes
Timepoint [5] 0 0
At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 168h, 336h and 504h between 43rd and 64th days of the study
Secondary outcome [6] 0 0
Cycle 3 AUC(0-tlast)md (AUC(0-tlast) after multiple-dose administration) of BAY94-9343 analytes
Timepoint [6] 0 0
At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 168h, 336h and 504h between 43rd and 64th days of the study

Eligibility
Key inclusion criteria
* Subjects must have histologically confirmed, locally advanced or metastatic solid cancers of the following histological types:

1. predominantly epithelial (=50% tumor component) pleural or peritoneal mesothelioma
2. epithelial ovarian cancer (fallopian tube and primary peritoneal cancers are eligible)
3. adenocarcinoma of the pancreas,
4. triple-negative adenocarcinoma of the breast
5. non-small-cell adenocarcinoma of the lung
6. gastric cancer (including gastro-esophageal junction)
7. colon cancer
8. cholangiocarcinoma
9. 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/09/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
5/08/2019
Sample size
Target
Accrual to date
Final
63
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Blacktown Cancer & Haematology Centre - Blacktown
Recruitment hospital [2] 0 0
Epworth HealthCare - Richmond
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
3122 - Richmond
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Belgium
State/province [6] 0 0
Bruxelles - Brussel
Country [7] 0 0
Belgium
State/province [7] 0 0
Gent
Country [8] 0 0
France
State/province [8] 0 0
Creteil
Country [9] 0 0
France
State/province [9] 0 0
Dijon
Country [10] 0 0
France
State/province [10] 0 0
Marseille
Country [11] 0 0
Netherlands
State/province [11] 0 0
Amsterdam
Country [12] 0 0
Netherlands
State/province [12] 0 0
Nijmegen
Country [13] 0 0
Spain
State/province [13] 0 0
Barcelona
Country [14] 0 0
Spain
State/province [14] 0 0
Madrid
Country [15] 0 0
Spain
State/province [15] 0 0
Málaga

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bayer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02824042