Solid TumorsPhase 1NCT02746081
Phase I Study of BAY1436032 in IDH1-mutant Advanced Solid Tumors
A Phase 1 study testing BAY1436032 in people with Solid Tumors, run by Bayer at 13 sites in 4 countries.
Trial summary
The primary objective of this study is: Determine the safety, tolerability, maximum tolerated dose (MTD) or recommended Phase II dose (RP2D) of BAY 1436032 in patients with isocitrate dehydrogenase-1 (IDH1)-R132X-mutant advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors
- What is being tested?
- BAY1436032
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- 13 sitesin 4 countries
- Study dates
- 26 May 2016to 3 Dec 2024
- 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 patients ≥ 18 years of age
- Patients with a histologically confirmed solid tumor:
- Tumor must harbor an IDH1-R132X mutation
- Disease must be evaluable as per RECIST 1.1 or RANO (for gliomas). At least one measurable target lesion is required in expansion cohort patients
- Patients with advanced cancer who are refractory to, have demonstrated intolerance to, or have refused access to, available standard therapies
- Glioma patients must have completed chemoradiotherapy at least 12 weeks prior to screening and their baseline scan
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- Patient must be able to provide a formalin-fixed and paraffin-embedded (FFPE) tumor tissue specimen prior to treatment. The specimen may have been taken at any time during the course of the disease and may be from the primary tumor or from a metastasis
- Patient must be able to take oral medication and comply with protocol procedures and scheduled visits
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Negative serum or urine pregnancy test must be obtained within 7 days prior to the first dose of study drug in women of childbearing potential. Negative results must be available prior to study drug administration. Pregnancy tests will be repeated regularly during treatment
- Sexually active women and men of reproductive potential must agree to use highly effective contraception. This applies for the period between signing of the informed consent and 3 months after the last administration of study drug. These procedures should be documented in source documents. The investigator or a designated associate is requested to advise the patient on how to achieve highly effective birth control. Highly effective contraception includes:
- Established use of oral, injected or implanted hormonal methods of contraception
- Placement of certain intrauterine devices (IUD) or intrauterine systems (IUS)
- Hysterectomy, or vasectomy of the partner (provided that partner is the sole sexual partner of the woman of childbearing potential trial participant and that the vasectomized partner has received medical assessment of the surgical success) In addition, the use of condoms for patients or their partners is required
- Ability to understand and the willingness to sign a written informed consent. A signed informed consent, including consent for biomarker analyses, must be obtained prior to any study-specific procedures
- Adequate blood clotting as defined by international normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 times ULN (patients on anticoagulation with an agent such as warfarin or heparin or rivoraxaban will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists). For patients on warfarin, close monitoring of at least weekly evaluations will be performed until INR is stable based on a measurement at pre-dose, as defined by the local standard of care
- Adequate bone marrow, liver, and renal functions as assessed by the following laboratory requirements to be conducted within 7 days prior to the first dose of study drug:
- Hemoglobin ≥ 9.0 g/dL;
- Absolute neutrophil count (ANC) ≥ 1.5x10^9/L;
- Platelet count ≥ 100x10^9/L.
- Total bilirubin ≤ 1.5 times the upper limit of normal (ULN). For intrahepatic cholangiocarcinoma (IHCC) patients only, total bilirubin ≤ 2.5 times ULN is acceptable
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times ULN (≤ 5 times ULN for patients with impaired liver function due primary tumor or metastatic disease)
- Estimated glomerular filtration rate (eGFR) ≥ 40 mL/min per 1.73 m^2 according to the Modification of Diet in Renal Disease Study Group (MDRD) formula
- Minimum life expectancy of 3 months per the judgment of the investigator
Who cannot join
- Known hypersensitivity to the study drug or excipients of the preparation or any agent given in association with this study
- History of cardiac disease, including congestive heart failure of New York Heart Association (NYHA) class >II, unstable angina (anginal symptoms at rest) or new-onset angina (within 6 months prior to study entry), myocardial infarction within 6 months prior to study entry, or cardiac arrhythmias requiring anti-arrhythmic therapy except for beta-blockers and digoxin; evidence for uncontrolled coronary artery disease (e.g. angina pectoris, myocardial infarction within 6 months prior to study entry, major regional wall motion abnormalities upon baseline echocardiography or multiple-gated acquisition [MUGA] scan). Patients with a pacemaker are also excluded
- Left ventricular ejection fraction (LVEF) < 40% as measured by echocardiography or MUGA scan performed at Screening
- Uncontrolled hypertension defined as systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg, despite medical management
- Patients who have an active clinically significant infection of the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2
- Previous or coexisting cancer(s) distinct in primary site or histology from the cancer evaluated in this study EXCEPT:
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- Appropriately treated cervical cancer in-situ, non-melanoma skin cancers, or superficial bladder tumors (Ta and Tis)
- Any cancer that was curatively treated at least 3 years before entry into this study
- Unresolved specific chronic toxicity of previous treatment of grade > 1 except for alopecia or hemoglobin ≤9.0 g/dL (or ≤5.6 mmol/L)
- Major surgery, significant trauma, wide-field radiotherapy, or therapy with monoclonal antibodies within 4 weeks before the first dose of study drug
- Treatment with investigational or approved anti-cancer drugs within 4 weeks before the start of BAY1436032 treatment and during the study (glioma patients must have completed chemoradiotherapy at least 12 weeks prior to screening and their baseline scan; see inclusion criteria #2)
- Pregnant women. Women of reproductive potential must have a negative serum or urine pregnancy test performed within 7 day
- Prior treatment with any therapy targeting mutant IDH1 (including BAY1436032)
Trial locations and contacts
13 sites in 4 countries.
13 sites in 4 countries
Germany5 sites
Study site
Essen, North Rhine-Westphalia, 45147
Study site
Frankfurt am Main, Hesse, 60590
Study site
Heidelberg, Baden-Wurttemberg, 69115
Study site
München, Bavaria, 81377
Study site
Tübingen, Baden-Wurttemberg, 72076
United States4 sites
Study site
Charlottesville, Virginia, 22903
Study site
Houston, Texas, 77030
Study site
Los Angeles, California, 90001
Study site
Los Angeles, California, 90012
Japan3 sites
Study site
Chuo-ku, Tokyo, 104-0045
Study site
Kashiwa, Chiba, 277-8577
Study site
Nagoya, Aichi-ken, 466-8560
About this study
Official title: An Open-label, Non-randomized, Multicenter Phase I Study to Determine the Maximum Tolerated or Recommended Phase II Dose of Oral Mutant IDH1 Inhibitor BAY1436032 and to Characterize Its Safety, Tolerability, Pharmacokinetics and Preliminary Pharmacodynamic and Anti-tumor Activity in Patients With IDH1-R132X-mutant Advanced Solid Tumors
The primary objective of this study is:
- Determine the safety, tolerability, maximum tolerated dose (MTD) or recommended Phase II dose (RP2D) of BAY 1436032 in patients with isocitrate dehydrogenase-1 (IDH1)-R132X-mutant advanced solid tumors.
The secondary objectives of this study are:
- Evaluate the pharmacokinetics (PK) of BAY1436032 in patients with IDH1-R132X-mutant advanced solid tumors.
- Evaluate the effect of a standard high-fat, high calorie meal on the PK of BAY1436032.
- Assess pharmacodynamic (PD) effects and evidence of clinical efficacy associated with BAY1436032 administration in patients with IDH1-R132X-mutant advanced solid tumors.
- Conditions
- Solid Tumors
- Being tested
- BAY1436032
- Keywords
- BAY1436032, Solid tumors, IDH1, Cancer, Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Efficacy, Food-effect
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BAY1436032Drug
The selected starting dose of BAY1436032 is 300 mg/day (150 mg BID) to be administered orally continuously in tablet form in 21-day cycles. Adjustments to this schedule may be made if warranted by information collected during the course of the study. The maximum feasible dose of BAY1436032 is expected to be 3000 mg/day.
| Study group | Role | What they receive |
|---|---|---|
| BAY1436032 | Experimental | Dose escalation: Patients with any type of IDH1-R132X-mutant solid tumor may be eligible for enrollment. A minimum of 3 patients per cohort will be treated. If dose limiting toxicities (DLTs) occur, Bayesian dose-DLT modeling will be performed to help guide dosing decisions and to identify the maximum tolerated dose (MTD). If the MTD is not reached, a recommended phase II dose (RP2D) will be chosen based on available safety, tolerability, PK, PD and clinical efficacy data.
Dose expansion: The dose and schedule that was determined to be most appropriate in the dose escalation part of the study, which may be the MTD and / or the RP2D, will be used. Cohorts will consist of patients with the following IDH-R132X-mutant tumor types: (1) anaplastic glioma; (2) glioblastoma; (3) intrahepatic cholangiocarcinoma; (4) tumor types other than those in Cohorts 1-3. Receives: Drug: BAY1436032 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) of BAY1436032
MTD is defined as the maximum dose at which the predicted incidence of DLTs during Cycle 1 (DLT evaluation period) is ≤25%.
Measured: 21 days
Number of participants with adverse events as a measure of safety and tolerability of BAY1436032
Safety and tolerability variables will include AEs, laboratory safety tests, ECGs, and vital signs.
Measured: Up to 30 months
Recommended Phase II Dose (RP2D) of BAY1436032
If the MTD is not reached, the primary variable will be the RP2D, defined based on all available safety, PK, PD, biomarker, and efficacy data collected after the start of BAY1436032 treatment.
Measured: Up to 20 months
Secondary outcomes (10)
Objective response rate (partial and complete response)
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or for gliomas Response Assessment in Neuro-Oncology (RANO)
Measured: Up to 30 months
Duration of response
Measured: Up to 30 months
Progression free survival (PFS)
For expansion part only
Measured: Up to 30 months
Cmax of BAY1436032
Measured: on C1D-2 and C1D1
AUC(0-12) of BAY1436032
Measured: on C1D-2 and C1D1
AUC(0-24) of BAY1436032
Measured: on C1D-2 and C1D1
C(max,md) of BAY1436032
Measured: on C1D15
AUC(0-12)md of BAY1436032
Measured: on C1D15
Change of 2-hydroxyglutarate (2-HG) concentration in plasma from baseline
Measured: Up to 30 months
Change of 2-hydroxyglutarate (2-HG) concentration in urine from baseline
Measured: Up to 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2016 (estimated)
- Study start26 May 2016
- Primary completion8 Nov 2018
- Study completion3 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorsStudies 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
- 81 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
- NCT02746081
- Sponsor's protocol ID
- 18239
- Other IDs
- 2015-003483-37, 2015
- Status last verified
- Dec 2024
- First submitted
- 8 Apr 2016
- Last updated
- 18 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2024. 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 Determine the Maximum Tolerated or Recommended Phase II Dose of Oral Mutant IDH1 Inhibitor BAY1436032 and to Characterize Its Safety, Tolerability, Pharmacokinetics and Preliminary Pharmacodynamic and Anti-tumor Activity in Patients With IDH1-R132X-mutant Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT02746081
- Acronym / sponsor ID
- 18239
- Conditions
- Solid Tumors
- Keywords
- BAY1436032, Solid tumors, IDH1, Cancer, Safety, Tolerability, Pharmacokinetics, Pharmacodynamics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 26 May 2016 (actual)
- Primary completion
- 8 Nov 2018 (actual)
- Study completion
- 3 Dec 2024 (actual)
- First posted
- 21 Apr 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.
The primary objective of this study is:
- Determine the safety, tolerability, maximum tolerated dose (MTD) or recommended Phase II dose (RP2D) of BAY 1436032 in patients with isocitrate dehydrogenase-1 (IDH1)-R132X-mutant advanced solid tumors.
The secondary objectives of this study are:
- Evaluate the pharmacokinetics (PK) of BAY1436032 in patients with IDH1-R132X-mutant advanced solid tumors.
- Evaluate the effect of a standard high-fat, high calorie meal on the PK of BAY1436032.
- Assess pharmacodynamic (PD) effects and evidence of clinical efficacy associated with BAY1436032 administration in patients with IDH1-R132X-mutant advanced solid tumors.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BAY1436032 | Experimental | Drug: BAY1436032Dose escalation: Patients with any type of IDH1-R132X-mutant solid tumor may be eligible for enrollment. A minimum of 3 patients per cohort will be treated. If dose limiting toxicities (DLTs) occur, Bayesian dose-DLT modeling will be performed to help guide dosing decisions and to identify the maximum tolerated dose (MTD). If the MTD is not reached, a recommended phase II dose (RP2D) will be chosen based on available safety, tolerability, PK, PD and clinical efficacy data. Dose expansion: The dose and schedule that was determined to be most appropriate in the dose escalation part of the study, which may be the MTD and / or the RP2D, will be used. Cohorts will consist of patients with the following IDH-R132X-mutant tumor types: (1) anaplastic glioma; (2) glioblastoma; (3) intrahepatic cholangiocarcinoma; (4) tumor types other than those in Cohorts 1-3. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Male or female patients ≥ 18 years of age
- Patients with a histologically confirmed solid tumor:
- Patient must be able to provide a formalin-fixed and paraffin-embedded (FFPE) tumor tissue specimen prior to treatment. The specimen may have been taken at any time during the course of the disease and may be from the primary tumor or from a metastasis
- Patient must be able to take oral medication and comply with protocol procedures and scheduled visits
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Key exclusion criteria (13 listed)
- Known hypersensitivity to the study drug or excipients of the preparation or any agent given in association with this study
- History of cardiac disease, including congestive heart failure of New York Heart Association (NYHA) class >II, unstable angina (anginal symptoms at rest) or new-onset angina (within 6 months prior to study entry), myocardial infarction within 6 months prior to study entry, or cardiac arrhythmias requiring anti-arrhythmic therapy except for beta-blockers and digoxin; evidence for uncontrolled coronary artery disease (e.g. angina pectoris, myocardial infarction within 6 months prior to study entry, major regional wall motion abnormalities upon baseline echocardiography or multiple-gated acquisition [MUGA] scan). Patients with a pacemaker are also excluded
- Left ventricular ejection fraction (LVEF) < 40% as measured by echocardiography or MUGA scan performed at Screening
- Uncontrolled hypertension defined as systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg, despite medical management
- Patients who have an active clinically significant infection of the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2
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 |
|---|---|---|
| BAY1436032The selected starting dose of BAY1436032 is 300 mg/day (150 mg BID) to be administered orally continuously in tablet form in 21-day cycles. Adjustments to this schedule may be made if warranted by information collected during the course of the study. The maximum feasible dose of BAY1436032 is expected to be 3000 mg/day. | Drug | BAY1436032 |
Primary outcome
Maximum tolerated dose (MTD) of BAY1436032
Time frame: 21 days
MTD is defined as the maximum dose at which the predicted incidence of DLTs during Cycle 1 (DLT evaluation period) is ≤25%.
Number of participants with adverse events as a measure of safety and tolerability of BAY1436032
Time frame: Up to 30 months
Safety and tolerability variables will include AEs, laboratory safety tests, ECGs, and vital signs.
Recommended Phase II Dose (RP2D) of BAY1436032
Time frame: Up to 20 months
If the MTD is not reached, the primary variable will be the RP2D, defined based on all available safety, PK, PD, biomarker, and efficacy data collected after the start of BAY1436032 treatment.
10 secondary outcomes
Objective response rate (partial and complete response)
Time frame: Up to 30 months
Duration of response
Time frame: Up to 30 months
Progression free survival (PFS)
Time frame: Up to 30 months
Cmax of BAY1436032
Time frame: on C1D-2 and C1D1
AUC(0-12) of BAY1436032
Time frame: on C1D-2 and C1D1
AUC(0-24) of BAY1436032
Time frame: on C1D-2 and C1D1
C(max,md) of BAY1436032
Time frame: on C1D15
AUC(0-12)md of BAY1436032
Time frame: on C1D15
Change of 2-hydroxyglutarate (2-HG) concentration in plasma from baseline
Time frame: Up to 30 months
Change of 2-hydroxyglutarate (2-HG) concentration in urine from baseline
Time frame: Up to 30 months
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 18 Dec 2024.
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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
13 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 BAY1436032 in people with Solid Tumors, run by Bayer at 13 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 24 inclusion and 13 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 18 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Germany, United States, Japan, Denmark. 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?
Maximum tolerated dose (MTD) of BAY1436032 (time frame: 21 days). 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 18 Dec 2024.