Phase I Study of BAY1436032 in IDH1-mutant Advanced Solid Tumors
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|ClinicalTrials.gov Identifier: NCT02746081|
Recruitment Status : Active, not recruiting
First Posted : April 21, 2016
Last Update Posted : April 23, 2021
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.
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumors||Drug: BAY1436032||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||81 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||May 26, 2016|
|Actual Primary Completion Date :||November 8, 2018|
|Estimated Study Completion Date :||December 31, 2021|
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.
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.
- 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.
- Objective response rate (partial and complete response) [ Time Frame: Up to 30 months ]Assessed by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or for gliomas Response Assessment in Neuro-Oncology (RANO)
- Duration of response [ Time Frame: Up to 30 months ]
- Progression free survival (PFS) [ Time Frame: Up to 30 months ]For expansion part only
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02746081
|United States, California|
|Los Angeles, California, United States, 90033|
|Santa Monica, California, United States, 90403|
|United States, Texas|
|Houston, Texas, United States, 77030|
|United States, Virginia|
|Charlottesville, Virginia, United States, 22908|
|Copenhagen, Denmark, 2100|
|Heidelberg, Baden-Württemberg, Germany, 69120|
|Tübingen, Baden-Württemberg, Germany, 72076|
|München, Bayern, Germany, 81377|
|Frankfurt, Hessen, Germany, 60596|
|Essen, Nordrhein-Westfalen, Germany, 45147|
|Nagoya, Aichi, Japan, 466-8560|
|Kashiwa-shi, Chiba, Japan, 277-8577|
|Chuo-ku, Tokyo, Japan, 104-0045|
|Study Director:||Bayer Study Director||Bayer|