Medical OncologyPhase 1NCT02439346
Phase I Dose Escalation and Expansion of Oral BAY 1143269 in Combination With Intravenous Docetaxel
A Phase 1 study testing BAY1143269 tablet in people with Medical Oncology, run by Bayer at 4 sites in 2 countries.
Trial summary
Determine the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics (PK), and/or recommended Phase II dose (RP2D) of oral BAY 1143269 given alone or in combination with intravenous (IV) docetaxel in subjects with advanced solid tumors. 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?
- BAY1143269 tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 15 Jun 2015to 24 Apr 2017
- 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
- Male or female subjects aged > 18 years
- Subjects must have histologically or cytologically confirmed locally advanced or metastatic solid tumors and must be refractory to any standard therapy, or have no standard therapy available, or have actively refused any standard therapy or, in the investigator's opinion, experimental treatment in this study is clinically and ethically acceptable for the subject.
- Subjects must have at least 1 measurable or evaluable tumor lesion according to RECIST 1.1 (Response Evaluation Criteria in Solid Tumors, version 1.1)
- Subjects must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Subjects must have a life expectancy of at least 12 weeks
- Subjects must have adequate bone marrow function as assessed by the following: hemoglobin >=9.0 g/dL or >=5.6 mmol/L, absolute neutrophil count (ANC) >=1.500/mm^3 or >=1.5 x 10^9/L (CTCAE Grade <=1), platelet count >= 100000/mm^3 or >=100 x 10^9/L
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- Subjects must have adequate kidney function, as assessed by the estimated glomerular filtration rate (eGFR) >=60 mL/min per 1.73 m*2 [Common Terminology Criteria for Adverse Events(CTCAE Grade <=1)] calculated by the Modification of Diet in Renal Disease Study Group (MDRD) formula
- Subjects must have adequate liver function assessed by: total bilirubin <= 1.0 x upper limit of normal (ULN), aspartate aminotransferase (ALT) <= 3.0 x ULN (CTCAE Grade <=1) or, if receiving BAY1143269 in combination with IV docetaxel, AST and ALT <=1.5 x ULN if concomitant with alkaline phosphatase increase >2.5 x ULN
- Subjects must have adequate coagulation as assessed by: international normalized ratio (INR) or prothrombin time (PT) <=1.5 times ULN (CTCAE Grade <=1), partial thromboplastin time (PTT) <=1.5 x ULN (CTCAE Grade <=1)
- Women of reproductive potential must have a negative serum beta human chorionic gonadotropin (b-HCG) pregnancy test within 7 days before the first dose of study drug. Women of reproductive potential and men with female partners of childbearing potential must agree to consistently use highly effective contraception between signing the informed consent and 60 days after the last administration of study drug
Who cannot join
- Subjects who have a 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 bladder tumors (Ta and Tis) or any previous cancer curatively treated <3 years before the first dose of study drug
- Subjects who have a history of, or current evidence of bleeding disorder, i.e. any hemorrhage / bleeding event of CTCAE Grade >= 2 <4 weeks before the first dose of study drug.
- Subjects who have new or progressive brain or meningeal or spinal metastases
- Subjects who have a history of, or current evidence of uncontrolled cardiovascular disease or a left ventricular ejection fraction (LVEF) <50%
- Women who are pregnant or breast-feeding
- Subjects experiencing unresolved toxicity of previous antitumor therapy (excluding alopecia) which is CTCAE Grade >1 at screening
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- Subjects who are current smokers or users of other tobacco products or have quit <90 days before first dose of study drug
- Subjects taking or likely to take strong and moderate CYP2D6 inhibitors, strong CYP1A1 inhibitors, and/or CYP1A1/CYP1A2 sensitive substrates or with narrow therapeutic index. Subjects receiving oral BAY1143269 and IV docetaxel must not take or be likely to take strong CYP3A1 inhibitors
- Subjects who have received systemic antitumor therapy within 4 weeks or radiotherapy to target lesions within 3 weeks before the first dose of study drug, which is longer
- Subjects who had received investigational drug treatment, including BAY1143269 and docetaxel, outside of this study within 4 weeks before the first dose of study drug, or for small molecules within the 5 half-lives of the agent before the first dose of study drug, whichever is longer
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
United States3 sites
Study site
Dallas, Texas, 75246
Study site
Houston, Texas, 77030
Study site
San Antonio, Texas, 78229
About this study
Official title: An Open-label, Non-randomized, Multicenter Phase I Study to Characterize the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Maximum Tolerated Dose of Oral MKNK1 Inhibitor BAY 1143269 Given Alone or in Combination With Intravenous Docetaxel in Subjects With Advanced Solid Tumors
Determine the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics (PK), and/or recommended Phase II dose (RP2D) of oral BAY 1143269 given alone or in combination with intravenous (IV) docetaxel in subjects with advanced solid tumors.
Read the detailed description
BAY 1143269 is a potent and selective, orally administered novel inhibitor of mitogen-activated protein kinase interacting serine/threonine-protein kinase 1 (MKNK1). MKNK1 activity is essential for the phosphorylation of eukaryotic translation initiation factor 4E (eIF4E), which promotes the synthesis of oncogenic proteins, inhibits apoptosis, and helps tumor cells survive under stress. Increased p-EIF4E levels were found in tumor tissues from cancer patients. MKNK also functions as a mediator of pro-inflammatory cytokine production.
Established anti-mitotic drugs such as vinca alkaloids, taxanes, or epothilones activate the spindle assembly checkpoint (SAC), a key surveillance mechanism that monitors the attachment of spindle microtubules to the kinetochores of the chromosomes during pro-metaphase and halts the transitions to anaphase until all chromosomes are bi-oriented, fully attached, and correctly tensed at the metaphase plate. These antimitotic drugs destabilize or stabilize the spindle microtubules and cause mitotic arrest. Prolonged arrest in mitosis forces a cell either into a mitotic exit without cytokinesis or into a mitotic catastrophe leading to cell death. MKNK1 inhibitors allow cell apoptosis and increase tumor death. The combination of taxane and MKNK1 inhibitor can ultimately delay tumor progression and may provide a useful anticancer therapeutic approach.
This study will attempt to answer the following questions:
- What is the maximum tolerated dose (MTD) of BAY 1143269 when given alone or in combination with docetaxel?
- What is the safety profile and pharmacokinetics of BAY1143269 when given at the MTD?
- What are the adverse events of BAY 1161909 when given at different dose levels with docetaxel?
- Conditions
- Medical Oncology
- Being tested
- BAY1143269 tablet
- Keywords
- Advanced solid tumors, Docetaxel, mitogen-activated protein (MAP) kinase-interacting serine / threonine-protein kinase 1, also known as Mnk1 (MKNK1 inhibitor), Taxanes, Non-small cell lung cancer
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BAY1143269 tabletDrug
BAY 1143269 5 mg or 25 mg tablet. Each treatment cycle will last 21 days.
| Study group | Role | What they receive |
|---|---|---|
| BAY1143269 5 mg | Experimental | Subjects received BAY1143269 5 milligram (mg) tablet orally, once daily (QD) from Day 1 to 21 in treatment cycle until evidence of tumor progression, unacceptable toxicity, consent withdrawal, or withdrawal from the study at the discretion of the investigator. A treatment cycle consisted of 21 days. Receives: Drug: BAY1143269 tablet |
| BAY1143269 10 mg | Experimental | Subjects received BAY1143269 10 mg (2*5 mg) tablet orally, QD from Day 1 to 21 in treatment cycle until evidence of tumor progression, unacceptable toxicity, consent withdrawal, or withdrawal from the study at the discretion of the investigator. A treatment cycle consisted of 21 days. Receives: Drug: BAY1143269 tablet |
| BAY1143269 25 mg | Experimental | Subjects received BAY1143269 25 mg tablet orally, QD from Day 1 to 21 in treatment cycle until evidence of tumor progression, unacceptable toxicity, consent withdrawal, or withdrawal from the study at the discretion of the investigator. A treatment cycle consisted of 21 days. Receives: Drug: BAY1143269 tablet |
| BAY1143269 50 mg | Experimental | Subjects received BAY1143269 50 mg (2*25 mg) tablet orally, QD from Day 1 to 21 in treatment cycle until evidence of tumor progression, unacceptable toxicity, consent withdrawal, or withdrawal from the study at the discretion of the investigator. A treatment cycle consisted of 21 days. Receives: Drug: BAY1143269 tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Oral BAY1143269 Alone and in Combination With Intravenous Docetaxel
The MTD of oral BAY1143269 given alone was defined as the maximum dose at which the predicted incidence of dose-limiting toxicities (DLTs) during Cycle 1 is below 30 percent (%).
Measured: Up to 2 years
Maximum Observed Drug Concentration (Cmax) in Plasma After Single and Multiple Dose Administration of BAY1143269
Maximum observed concentration of BAY1143269 in plasma after single dose and multiple dose administration was measured.
Measured: Cycle 1, 2 Day 1: Pre-dose to 24 hours post-dose
Area Under the Concentration-time Curve From Time Zero to 24 Hours [AUC(0-24)] After Single and Multiple Dose Administration of BAY1143269
Area under the concentration-time curve from zero to 24 hours after single dose and multiple dose administration of BAY1143269 in plasma was measured.
Measured: Cycle 1, 2 Day 1: Pre-dose to 24 hours post-dose
Secondary outcomes (1)
Tumor response
Tumor response was assessed by Response Evaluation Criteria in Solid Tumors(RECIST V1.1). Evaluation of target lesions included CR(Disappearance of all target lesions),PR(at least a 30% decrease in sum of diameters of target lesions),PD:at least a 20% increase in sum of diameters of target lesions, taking smallest sum recorded as reference since treatment started or appearance of one or more new lesions) and Stable disease(SD:neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD).Evaluation of non-target lesions included CR(disappearance of all non-target lesions and normalization of tumor marker level),Non-CR/PD(Persistence of 1 or more non target lesions and/or maintenance of tumor marker level above normal limits) and PD(Appearance of 1 or more new lesions and/or unequivocal progression of existing non target lesions).
Measured: Baseline; end of Cycle 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2015 (estimated)
- Study start15 Jun 2015
- Primary completion27 Mar 2017
- Study completion24 Apr 2017
Why it stopped: Study stopped due to project prioritization
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 15 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
- NCT02439346
- Sponsor's protocol ID
- 17450
- Other IDs
- 2014-004810-27, 2014
- Status last verified
- Mar 2018
- First submitted
- 7 May 2015
- Last updated
- 7 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Luo H, Huang S. Inhibition of MNK pathway sensitizes nasopharyngeal carcinoma to radiotherapy. Anticancer Drugs. 2024 Feb 1;35(2):155-162. doi: 10.1097/CAD.0000000000001542. Epub 2023 Sep 11.
PubMed 37694854
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Non-randomized, Multicenter Phase I Study to Characterize the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Maximum Tolerated Dose of Oral MKNK1 Inhibitor BAY 1143269 Given Alone or in Combination With Intravenous Docetaxel in Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT02439346
- Acronym / sponsor ID
- 17450
- Conditions
- Medical Oncology
- Keywords
- Advanced solid tumors, Docetaxel, mitogen-activated protein (MAP) kinase-interacting serine / threonine-protein kinase 1, also known as Mnk1 (MKNK1 inhibitor), Taxanes, Non-small cell lung cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study stopped due to project prioritization
- Enrolment
- 15 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 15 Jun 2015 (actual)
- Primary completion
- 27 Mar 2017 (actual)
- Study completion
- 24 Apr 2017 (actual)
- First posted
- 8 May 2015 (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.
Determine the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics (PK), and/or recommended Phase II dose (RP2D) of oral BAY 1143269 given alone or in combination with intravenous (IV) docetaxel in subjects with advanced solid tumors.
Detailed description
BAY 1143269 is a potent and selective, orally administered novel inhibitor of mitogen-activated protein kinase interacting serine/threonine-protein kinase 1 (MKNK1). MKNK1 activity is essential for the phosphorylation of eukaryotic translation initiation factor 4E (eIF4E), which promotes the synthesis of oncogenic proteins, inhibits apoptosis, and helps tumor cells survive under stress. Increased p-EIF4E levels were found in tumor tissues from cancer patients. MKNK also functions as a mediator of pro-inflammatory cytokine production.
Established anti-mitotic drugs such as vinca alkaloids, taxanes, or epothilones activate the spindle assembly checkpoint (SAC), a key surveillance mechanism that monitors the attachment of spindle microtubules to the kinetochores of the chromosomes during pro-metaphase and halts the transitions to anaphase until all chromosomes are bi-oriented, fully attached, and correctly tensed at the metaphase plate. These antimitotic drugs destabilize or stabilize the spindle microtubules and cause mitotic arrest. Prolonged arrest in mitosis forces a cell either into a mitotic exit without cytokinesis or into a mitotic catastrophe leading to cell death. MKNK1 inhibitors allow cell apoptosis and increase tumor death. The combination of taxane and MKNK1 inhibitor can ultimately delay tumor progression and may provide a useful anticancer therapeutic approach.
This study will attempt to answer the following questions:
- What is the maximum tolerated dose (MTD) of BAY 1143269 when given alone or in combination with docetaxel?
- What is the safety profile and pharmacokinetics of BAY1143269 when given at the MTD?
- What are the adverse events of BAY 1161909 when given at different dose levels with docetaxel?
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| BAY1143269 5 mg | Experimental | Drug: BAY1143269 tabletSubjects received BAY1143269 5 milligram (mg) tablet orally, once daily (QD) from Day 1 to 21 in treatment cycle until evidence of tumor progression, unacceptable toxicity, consent withdrawal, or withdrawal from the study at the discretion of the investigator. A treatment cycle consisted of 21 days. |
| BAY1143269 10 mg | Experimental | Drug: BAY1143269 tabletSubjects received BAY1143269 10 mg (2*5 mg) tablet orally, QD from Day 1 to 21 in treatment cycle until evidence of tumor progression, unacceptable toxicity, consent withdrawal, or withdrawal from the study at the discretion of the investigator. A treatment cycle consisted of 21 days. |
| BAY1143269 25 mg | Experimental | Drug: BAY1143269 tabletSubjects received BAY1143269 25 mg tablet orally, QD from Day 1 to 21 in treatment cycle until evidence of tumor progression, unacceptable toxicity, consent withdrawal, or withdrawal from the study at the discretion of the investigator. A treatment cycle consisted of 21 days. |
| BAY1143269 50 mg | Experimental | Drug: BAY1143269 tabletSubjects received BAY1143269 50 mg (2*25 mg) tablet orally, QD from Day 1 to 21 in treatment cycle until evidence of tumor progression, unacceptable toxicity, consent withdrawal, or withdrawal from the study at the discretion of the investigator. A treatment cycle consisted of 21 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female subjects aged > 18 years
- Subjects must have histologically or cytologically confirmed locally advanced or metastatic solid tumors and must be refractory to any standard therapy, or have no standard therapy available, or have actively refused any standard therapy or, in the investigator's opinion, experimental treatment in this study is clinically and ethically acceptable for the subject.
- Subjects must have at least 1 measurable or evaluable tumor lesion according to RECIST 1.1 (Response Evaluation Criteria in Solid Tumors, version 1.1)
- Subjects must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Subjects must have a life expectancy of at least 12 weeks
Key exclusion criteria (10 listed)
- Subjects who have a 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 bladder tumors (Ta and Tis) or any previous cancer curatively treated <3 years before the first dose of study drug
- Subjects who have a history of, or current evidence of bleeding disorder, i.e. any hemorrhage / bleeding event of CTCAE Grade >= 2 <4 weeks before the first dose of study drug.
- Subjects who have new or progressive brain or meningeal or spinal metastases
- Subjects who have a history of, or current evidence of uncontrolled cardiovascular disease or a left ventricular ejection fraction (LVEF) <50%
- Women who are pregnant or breast-feeding
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 |
|---|---|---|
| BAY1143269 tabletBAY 1143269 5 mg or 25 mg tablet. Each treatment cycle will last 21 days. | Drug | BAY1143269 10 mg, BAY1143269 25 mg, BAY1143269 5 mg, BAY1143269 50 mg |
Primary outcome
Maximum Tolerated Dose (MTD) of Oral BAY1143269 Alone and in Combination With Intravenous Docetaxel
Time frame: Up to 2 years
The MTD of oral BAY1143269 given alone was defined as the maximum dose at which the predicted incidence of dose-limiting toxicities (DLTs) during Cycle 1 is below 30 percent (%).
Maximum Observed Drug Concentration (Cmax) in Plasma After Single and Multiple Dose Administration of BAY1143269
Time frame: Cycle 1, 2 Day 1: Pre-dose to 24 hours post-dose
Maximum observed concentration of BAY1143269 in plasma after single dose and multiple dose administration was measured.
Area Under the Concentration-time Curve From Time Zero to 24 Hours [AUC(0-24)] After Single and Multiple Dose Administration of BAY1143269
Time frame: Cycle 1, 2 Day 1: Pre-dose to 24 hours post-dose
Area under the concentration-time curve from zero to 24 hours after single dose and multiple dose administration of BAY1143269 in plasma was measured.
1 secondary outcome
Tumor response
Time frame: Baseline; end of Cycle 2
Results and safety
The study was stopped early (reason given: Study stopped due to project prioritization). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2018.
- Derived from this study: PubMed 37694854Luo H, Huang S. Inhibition of MNK pathway sensitizes nasopharyngeal carcinoma to radiotherapy. Anticancer Drugs. 2024 Feb 1;35(2):155-162. doi: 10.1097/CAD.0000000000001542. Epub 2023 Sep 11.
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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
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BAY1143269 tablet in people with Medical Oncology, run by Bayer at 4 sites in 2 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 10 inclusion and 10 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: stopped early, as of the sponsor's last update on 7 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, United Kingdom. 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 was stopped early (reason given: Study stopped due to project prioritization). Results are not available in the source record.
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?
Maximum Tolerated Dose (MTD) of Oral BAY1143269 Alone and in Combination With Intravenous Docetaxel (time frame: Up to 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02439346, which also lists 1 linked publication.
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 7 Mar 2018.