This study is open to Japanese adults with different types of advanced cancer that are positive for NRAS/KRAS mutations. This is a study in people for whom previous treatment was not successful or no standard treatment exists. The purpose of this study is to find the highest dose of BI 3011441 that Japanese people with advanced cancer can tolerate. BI 3011441 is a medicine that may turn off a signal by NRAS/KRAS that makes tumours grow. Participants take BI 3011441 as capsules once a day. Participants can stay in the study as long as they benefit from treatment and can tolerate it. The doctors collect information on any health problems of the participants.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
BI 3011441
National Cancer Center Hospital East
Chiba, Kashiwa, Japan
National Cancer Center Hospital
Tokyo, Chuo-ku, Japan
Japanese Foundation for Cancer Research
Tokyo, Koto-ku, Japan
Number of Patients With DLTs in the MTD Evaluation Period
Number of participants with Dose limiting toxicities (DLT) occurring during the first treatment cycle (first 4 weeks). DLT was defined as any of the following adverse events related to the treatment: * Haematologic toxicities: * Neutropenia Grade 4 lasting for \>7 days days without documented infection * Neutropenia Grade ≥3 with documented infection * Grade ≥3 febrile neutropenia * Grade 4 neutropenia defined as life-threatening consequences or urgent intervention indicated * Grade 5 neutropenia defined as a fatal neutropenia * Grade 3 thrombocytopenia associated with bleeding
Time frame: First treatment cycle, the first 28 days following the start of trial medication.
Maximum Tolerated Dose (MTD) of BI 3011441 Monotherapy
Maximum tolerated dose (MTD) of BI 3011441 monotherapy. The MTD was defined as the highest dose with less than 25% risk of the true dose-limiting toxicity (DLT) rate being equal or above 0.33 (EWOC criterion) during the MTD evaluation period. The analysis of the MTD was based on a Bayesian 2-parameter logistic regression model (BLRM) with overdose control.
Time frame: First treatment cycle, the first 28 days following the start of trial medication.
Number of Patients With DLTs During the Entire On-treatment Period
Number of participants with Dose limiting toxicities (DLT) occurring during the first treatment cycle (first 4 weeks). DLT was defined as any of the following adverse events related to the treatment: * Haematologic toxicities: * Neutropenia Grade 4 lasting for \>7 days days without documented infection * Neutropenia Grade ≥3 with documented infection * Grade ≥3 febrile neutropenia * Grade 4 neutropenia defined as life-threatening consequences or urgent intervention indicated * Grade 5 neutropenia defined as a fatal neutropenia * Grade 3 thrombocytopenia associated with bleeding
Time frame: From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days.
Number of Patients With Grade ≥3 Treatment-related Adverse Events
Number of participants with Grade ≥3 treatment-related adverse events is reported. The severity of AEs were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. The CTCAE grades are Grade 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).
Time frame: From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days.
Number of Patients With Treatment Related Adverse Events
Number of participants with drug-related adverse events (AEs) analysed as investigator defined drug-related AEs is presented. Medical judgment was used to determine the relationship between the AEs and the study medication, considering all relevant factors, including pattern of reaction, temporal relationship, de-challenge or re-challenge, confounding factors such as concomitant medication, concomitant diseases and relevant history.
Time frame: From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days.
Area Under the Concentration-time Curve of BI 3011441 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of BI 3011441 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported.
Time frame: Cycle 1: Day 1: Within 5 minutes (min) before and 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h and optionally 12h. and Day 2 : Within 5 minutes (min) before dosing on Day 2.
Area Under the Concentration-time Curve of BI 3011441 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point at Steady State (AUC0-tz,ss)
Area under the concentration-time curve of BI 3011441 in plasma over the time interval from 0 to the last quantifiable data point at steady state (AUC0-tz,ss) is reported.
Time frame: Cycle 1: Day 15: Within 5 minutes (min) before drug administration on Day 15, and 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h and optionally 12h. and Day 16 : Within 5 minutes (min) before dosing on Day 16.
Maximum Measured Concentration of BI 3011441 in Plasma After First Dose (Cmax)
Maximum measured concentration of BI 3011441 in plasma (Cmax) is reported.
Time frame: Cycle 1: Day 1: Within 5 minutes (min) before and 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h and optionally 12h. and Day 2 : Within 5 minutes (min) before dosing on Day 2.
Maximum Measured Concentration of BI 3011441 in Plasma at Steady State (Cmax,ss)
Maximum measured concentration of BI 3011441 in plasma at steady state (Cmax,ss) is reported. PK samples were collected at the following timepoints.
Time frame: Cycle 1: Day 15: Within 5 minutes (min) before drug administration on Day 15, and 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h and optionally 12h. and Day 16 : Within 5 minutes (min) before dosing on Day 16.
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