NeoplasmsPhase 1NCT01915576
Phase I Dose Escalation Study With an Allosteric AKT 1/2 Inhibitor in Patients
A Phase 1 study testing BAY1125976 in people with Neoplasms, run by Bayer at 7 sites in 4 countries.
Trial summary
This is the first study where BAY1125976 is given to humans. Patients (all comers) will receive the study drug treatment in a dose-escalation scheme (no placebo group) to determine the safety, tolerability and maximum tolerated dose (MTD) of BAY1125976. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- BAY1125976
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 79 participants
- Where
- 7 sitesin 4 countries
- Study dates
- Sep 2013to Dec 2016
- 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
- For dose escalation cohorts: Subjects with advanced, histologically or cytologically confirmed solid tumors are eligible. Subjects' tumors (all comers) must be refractory to standard treatment with no standard therapy available, or subjects actively refuse any treatment, which would be regarded standard. In addition, the investigator must judge the experimental treatment as clinically and ethically acceptable
- For expansion cohort only: Subjects with histologically or cytologically proven metastatic breast cancer (with and without AKT1 E17K (G49A) mutation) or subjects with known AKT1 E17K (G49A) mutation in any other advanced solid tumor with at least one line of chemotherapy in the metastatic setting and not amenable to surgery with curative intent
- Subjects must have measurable disease (Response evaluation criteria in solid tumors (RECIST 1.1)
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 2
- Bone marrow, liver and renal functions as assessed by adequate laboratory methods to be conducted within 7 days prior to starting study treatment
- Subjects must provide tumor biopsies before treatment
- Recovery to CTCAE (Common Terminology Criteria for Adverse Events Version 4.03) Grade 0 or Grade 1 or recovery to baseline preceding the prior treatment of any previous drug / procedure-related toxicity (except alopecia, anemia, and hypothyroidism)
Who cannot join
- History of cardiac disease including congestive heart failure > New York Heart Association (NYHA) Class II
- Subjects with type 1 or type 2 diabetes mellitus
- Subjects with fasting glucose >125 mg/dL in 2 independent measurements or glycated hemoglobin (HbA1c) ≥ 7%
- Moderate and severe hepatic impairment, i.e. Child-Pugh B or C
- Active infections of CTCAE (Common Terminology Criteria for Adverse Events Version 4.03) Grade >2 or infections of CTCAE Grade 2 not responding to therapy
- Symptomatic metastatic brain or meningeal tumors unless the patient is > 3 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry.
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- Subjects undergoing renal dialysis
- 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, Tis \& T1) or any cancer curatively treated > 3 years prior to study entry
- Autologous bone marrow transplant or stem cell rescue within 4 months of study entry
- Treatment with oral steroids (dose ≥ 10 mg/day of methylprednisolone or equivalent)
- Clinically relevant findings in the ECG such as a second- or third-degree AV block, prolongation of the QRS complex over 120 msec or of the QTcF-interval over 450 msec
- Acute toxic effects of previous anticancer chemotherapy or immunotherapy have to be normalized to CTCAE Grade equal or lower than 1 (excluding alopecia)
Trial locations and contacts
7 sites in 4 countries.
7 sites in 4 countries
United States4 sites
Study site
Boston, Massachusetts, 02215
Study site
Houston, Texas, 77030
Study site
Santa Monica, California, 90404
Study site
St Louis, Missouri, 63110
About this study
Official title: A Phase I, Multi-center, Non-randomized, Open-label, Dose Escalation Design Study to Characterize Safety, Tolerability, Pharmacokinetics and Maximum Tolerated Dose of BAY 1125976 in Subjects With Advanced Solid Tumors
This is the first study where BAY1125976 is given to humans. Patients (all comers) will receive the study drug treatment in a dose-escalation scheme (no placebo group) to determine the safety, tolerability and maximum tolerated dose (MTD) of BAY1125976. The relative bioavailability of liquid service formulation and tablets will be determined.
After the MTD is defined breast cancer patients with and without AKT1 mutation will be treated.
Read more
The study will also assess the pharmacokinetics, biomarker status, pharmacodynamic parameters and tumor response of BAY1125976.
BAY1125976 will be given daily as single oral application. Treatment will be stopped if the tumor continues to grow, if side effects, which the patient cannot tolerate, occur or if the patient decides to exit treatment.
- Conditions
- Neoplasms
- Being tested
- BAY1125976
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BAY1125976Drug
Oral administration once daily. Starting dose is 10 mg and will be escalated depending on any dose-limiting toxicities
BAY1125976Drug
Oral administration twice daily. Starting dose is 40mg twice daily and will be escalated depending on any dose-limiting toxicities
BAY1125976Drug
Oral administration of the defined MTD which shows optimal safety, PK profile, PD target inhibition and preliminary efficacy (once daily or twice daily) in different patient groups
| Study group | Role | What they receive |
|---|---|---|
| BAY1125976 [once daily, dose-esc.] | Experimental | Oral administration once daily. Starting dose is 10 mg and will be escalated depending on any dose-limiting toxicities Receives: Drug: BAY1125976 |
| BAY1125976 [twice daily, dose-esc.] | Experimental | Oral administration twice daily. Starting dose is 40mg twice daily and will be escalated depending on any dose-limiting toxicities Receives: Drug: BAY1125976 |
| BAY1125976 [MTD] | Experimental | Oral administration of the defined MTD which shows optimal safety, PK profile, PD target inhibition and preliminary efficacy (once daily or twice daily) in different patient groups Receives: Drug: BAY1125976 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events as a measure of safety and tolerability
Measured: up to 2 years
Maximum tolerated dose (MTD) of BAY1125976
Measured: up to 2 years
Area under the plasma concentration vs time curve from zero to infinity after single (first) dose
Measured: at pre-dose and 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose
Secondary outcomes (2)
Food effect assessment
The effect of a high-fat, high-calorie meal on the pharmacokinetic parameters of BAY1125976 will be determined in 6 - 9 subjects in the MTD dose level or a lower dose level receiving the tablet for the cohort of the dose escalation part.
Measured: up to 2 years
Tumor response will be evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST) definitions
Measured: up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2013 (estimated)
- Study startSep 2013
- Primary completionJul 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeoplasmsStudies 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
- Single group
- Masking
- None (open label)
- Enrolment
- 79 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
- NCT01915576
- Sponsor's protocol ID
- 16447
- Other IDs
- 2012-004671-39
- Status last verified
- Dec 2016
- First submitted
- 29 Jul 2013
- Last updated
- 28 Dec 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Multi-center, Non-randomized, Open-label, Dose Escalation Design Study to Characterize Safety, Tolerability, Pharmacokinetics and Maximum Tolerated Dose of BAY 1125976 in Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01915576
- Acronym / sponsor ID
- 16447
- Conditions
- Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- Sep 2013
- Primary completion
- Jul 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 5 Aug 2013 (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.
This is the first study where BAY1125976 is given to humans. Patients (all comers) will receive the study drug treatment in a dose-escalation scheme (no placebo group) to determine the safety, tolerability and maximum tolerated dose (MTD) of BAY1125976. The relative bioavailability of liquid service formulation and tablets will be determined.
After the MTD is defined breast cancer patients with and without AKT1 mutation will be treated.
The study will also assess the pharmacokinetics, biomarker status, pharmacodynamic parameters and tumor response of BAY1125976.
BAY1125976 will be given daily as single oral application. Treatment will be stopped if the tumor continues to grow, if side effects, which the patient cannot tolerate, occur or if the patient decides to exit treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| BAY1125976 [once daily, dose-esc.] | Experimental | Drug: BAY1125976Oral administration once daily. Starting dose is 10 mg and will be escalated depending on any dose-limiting toxicities |
| BAY1125976 [twice daily, dose-esc.] | Experimental | Drug: BAY1125976Oral administration twice daily. Starting dose is 40mg twice daily and will be escalated depending on any dose-limiting toxicities |
| BAY1125976 [MTD] | Experimental | Drug: BAY1125976Oral administration of the defined MTD which shows optimal safety, PK profile, PD target inhibition and preliminary efficacy (once daily or twice daily) in different patient groups |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- For dose escalation cohorts: Subjects with advanced, histologically or cytologically confirmed solid tumors are eligible. Subjects' tumors (all comers) must be refractory to standard treatment with no standard therapy available, or subjects actively refuse any treatment, which would be regarded standard. In addition, the investigator must judge the experimental treatment as clinically and ethically acceptable
- For expansion cohort only: Subjects with histologically or cytologically proven metastatic breast cancer (with and without AKT1 E17K (G49A) mutation) or subjects with known AKT1 E17K (G49A) mutation in any other advanced solid tumor with at least one line of chemotherapy in the metastatic setting and not amenable to surgery with curative intent
- Subjects must have measurable disease (Response evaluation criteria in solid tumors (RECIST 1.1)
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 2
- Bone marrow, liver and renal functions as assessed by adequate laboratory methods to be conducted within 7 days prior to starting study treatment
Key exclusion criteria (12 listed)
- History of cardiac disease including congestive heart failure > New York Heart Association (NYHA) Class II
- Subjects with type 1 or type 2 diabetes mellitus
- Subjects with fasting glucose >125 mg/dL in 2 independent measurements or glycated hemoglobin (HbA1c) ≥ 7%
- Moderate and severe hepatic impairment, i.e. Child-Pugh B or C
- Active infections of CTCAE (Common Terminology Criteria for Adverse Events Version 4.03) Grade >2 or infections of CTCAE Grade 2 not responding to therapy
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 |
|---|---|---|
| BAY1125976Oral administration once daily. Starting dose is 10 mg and will be escalated depending on any dose-limiting toxicities | Drug | BAY1125976 [once daily, dose-esc.] |
| BAY1125976Oral administration twice daily. Starting dose is 40mg twice daily and will be escalated depending on any dose-limiting toxicities | Drug | BAY1125976 [twice daily, dose-esc.] |
| BAY1125976Oral administration of the defined MTD which shows optimal safety, PK profile, PD target inhibition and preliminary efficacy (once daily or twice daily) in different patient groups | Drug | BAY1125976 [MTD] |
Primary outcome
Number of participants with adverse events as a measure of safety and tolerability
Time frame: up to 2 years
Maximum tolerated dose (MTD) of BAY1125976
Time frame: up to 2 years
Area under the plasma concentration vs time curve from zero to infinity after single (first) dose
Time frame: at pre-dose and 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose
2 secondary outcomes
Food effect assessment
Time frame: up to 2 years
Tumor response will be evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST) definitions
Time frame: up to 2 years
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 28 Dec 2016.
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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
7 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BAY1125976 in people with Neoplasms, run by Bayer at 7 sites in 4 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 7 inclusion and 12 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 28 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, France, Germany, Switzerland. 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?
Number of participants with adverse events as a measure of safety and tolerability (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?
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 28 Dec 2016.