Medical OncologyPhase 1NCT02824042
Thorough ECG (Electrocardiogram) and Drug Interaction Study With Anetumab Ravtansine and Itraconazole
A Phase 1 study testing Anetumab ravtansine (BAY94-9343) and Itraconazole in people with Medical Oncology, run by Bayer at 18 sites in 6 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Medical Oncology
- What is being tested?
- Anetumab ravtansine (BAY94-9343) and Itraconazole
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 18 sitesin 6 countries
- Study dates
- 7 Sep 2016to 5 Aug 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- gastric cancer (including gastro-esophageal junction)
- colon cancer
- cholangiocarcinoma
- 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.
Who cannot join
- 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
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- 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 locations and contacts
18 sites in 6 countries.
18 sites in 6 countries
United States5 sites
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106-2602
Mary Crowley Medical Research Center
Dallas, Texas, 75230
Henry Ford Health System
Detroit, Michigan, 48202
UCLA-Santa Monica Medical Center
Santa Monica, California, 90404
Washington University School of Medicine
St Louis, Missouri, 63110
France3 sites
Hôpital Henri Mondor
Créteil, 94010
Centre Georges Francois Leclerc Dijon
Dijon, 21079
Hôpital de la Timone - Marseille
Marseille, 13005
Netherlands3 sites
Nederlands Kanker Instituut
Amsterdam, 1066 CX
VUmc
Amsterdam, 1081 HV
Universitair Medisch Centrum St. Radboud
Nijmegen, 6525 GA
Spain3 sites
Ciutat Sanitària i Universitaria de la Vall d'Hebron
Barcelona, 08035
Fundacion Jimenez Diaz (Clinica de la Concepcion)
Madrid, 28040
Hospital Virgen de la Victoria
Málaga, 29010
Australia2 sites
Blacktown Cancer & Haematology Centre
Blacktown, New South Wales, 2148
Epworth HealthCare
Richmond, Victoria, 3122
Belgium2 sites
CU Saint-Luc/UZ St-Luc
Bruxelles - Brussel, 1200
UZ Gent
Ghent, 9000
About this study
Official 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
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
- Conditions
- Medical Oncology
- Being tested
- Anetumab ravtansine (BAY94-9343), Itraconazole
- Keywords
- Phase 1, Solid tumors, Mesothelin, Itraconazole, PK DDI, ECG thorough QTC
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anetumab ravtansine (BAY94-9343)Drug
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)
ItraconazoleDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| Anetumab ravtansine | Experimental | 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. Receives: Drug: Anetumab ravtansine (BAY94-9343); Drug: Itraconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
PR interval duration
ECG evaluation
Measured: Up to 2 months per patient
QRS interval duration
ECG evaluation
Measured: Up to 2 months per patient
QT interval duration
ECG evaluation
Measured: Up to 2 months per patient
Abnormal T/U waves
ECG evaluation
Measured: Up to 2 months per patient
Heart rate
ECG evaluation
Measured: Up to 2 months per patient
Cycle 1+2 AUC (area under the plasma concentration vs. time curve from zero to infinity after single (first) dose) of BAY94-9343 analytes
Measured: 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 AUC(0-tlast) (AUC from time zero to the last data point > LLOQ [lower limit of quantification]) of BAY94-9343 analytes
Measured: 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
Measured: 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
ECG evaluation
Measured: Up to 2 months per patient
QTcP (QT interval, corrected for heart rate using a population-specific correction) interval duration
ECG evaluation
Measured: Up to 2 months per patient
Secondary outcomes (6)
Incidence of serious adverse events
Measured: Up to 6 months per patient
Incidence of non-serious adverse events
Measured: Up to 6 months per patient
Incidence of positive anti-drug antibody titer
Measured: Up to 6 months per patient
Incidence of neutralizing antibody titers
Measured: Up to 6 months per patient
Cycle 3 Cmax,md (Cmax after multiple-dose administration) of BAY94-9343 analytes
Measured: 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
Measured: At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 168h, 336h and 504h between 43rd and 64th days of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2016 (estimated)
- Study start7 Sep 2016
- Primary completion27 Jun 2018
- Study completion5 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Medical OncologyStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bayer Study Director, Study director, Bayer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02824042
- Sponsor's protocol ID
- 18329
- Other IDs
- 2017-001978-42, 2017
- Status last verified
- Jul 2020
- First submitted
- 27 Jun 2016
- Last updated
- 31 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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.
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02824042
- Acronym / sponsor ID
- 18329
- Conditions
- Medical Oncology
- Keywords
- Phase 1, Solid tumors, Mesothelin, Itraconazole, PK DDI, ECG thorough QTC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 7 Sep 2016 (actual)
- Primary completion
- 27 Jun 2018 (actual)
- Study completion
- 5 Aug 2019 (actual)
- First posted
- 6 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anetumab ravtansine | Experimental | Drug: Anetumab ravtansine (BAY94-9343), Drug: ItraconazoleThe 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Subjects must have histologically confirmed, locally advanced or metastatic solid cancers of the following histological types:
- 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
Key exclusion criteria (16 listed)
- 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
- Had a major surgery or significant trauma within 4 weeks before the start of anetumab ravtansine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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) | Drug | Anetumab ravtansine |
| ItraconazoleItraconazole 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) | Drug | Anetumab ravtansine |
Primary outcome
PR interval duration
Time frame: Up to 2 months per patient
ECG evaluation
QRS interval duration
Time frame: Up to 2 months per patient
ECG evaluation
QT interval duration
Time frame: Up to 2 months per patient
ECG evaluation
Abnormal T/U waves
Time frame: Up to 2 months per patient
ECG evaluation
Heart rate
Time frame: 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
Time 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
Cycle 1+2 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, 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
Time 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
QTcF (QT interval, corrected for heart rate according to Fridericia's formula) interval duration
Time frame: Up to 2 months per patient
ECG evaluation
QTcP (QT interval, corrected for heart rate using a population-specific correction) interval duration
Time frame: Up to 2 months per patient
ECG evaluation
6 secondary outcomes
Incidence of serious adverse events
Time frame: Up to 6 months per patient
Incidence of non-serious adverse events
Time frame: Up to 6 months per patient
Incidence of positive anti-drug antibody titer
Time frame: Up to 6 months per patient
Incidence of neutralizing antibody titers
Time frame: Up to 6 months per patient
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, 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
Time 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2020.
- Click here to find information about studies related to Bayer Healthcare products conducted in EuropeLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bayer Study Director study director
Bayer
18 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Anetumab ravtansine (BAY94-9343) and Itraconazole in people with Medical Oncology, run by Bayer at 18 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, France, Netherlands, Spain, Australia and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PR interval duration (time frame: Up to 2 months per patient). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2020.