A Study to Test Different Doses of BI 891065 Alone and in Combination With BI 754091 in Asian Patients With Different Types of Advanced Cancer (Solid Tumours)
- Conditions
- Neoplasm
- Interventions
- Drug: BI 891065
- Registration Number
- NCT04138823
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
The primary objective of this trial is:
Part A
- To determine the Maximum tolerated dose (MTD) and/or the recommended dose (RD) of BI 891065 monotherapy for further development in Asian patients with advanced solid tumours
Part B
- To determine the MTD and/or the RD of BI 891065 in combination with a fixed dose of BI 754091 at 240 mg for further development in Asian patients with advanced solid tumours
The secondary objectives are:
Part A
- To document the safety and tolerability, and characterise pharmacokinetics (PK) of BI 891065 as monotherapy in Asian patients with advanced solid tumours
Part B
- To document the safety and tolerability, and characterise PK of the combination therapy of BI 891065 and BI 754091 in Asian patients with advanced solid tumours
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 12
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A: 100 mg BI 891065 QD BI 891065 - Part A: 200 mg BI 891065 QD BI 891065 - Part A: 200 mg BI 891065 BID BI 891065 -
- Primary Outcome Measures
Name Time Method Part A: Number of Patients With Dose Limiting Toxicities (DLTs) in the MTD Evaluation Period First treatment cycle, 21 days from first administration of BI 891065. Any of the following adverse events (AEs) were classified as DLTs:
Haematologic toxicities:
* Any Grade 5 toxicity.
* Neutropenia ≥ Grade 4 lasting for \>7 days.
* Febrile neutropenia of any duration (absolute neutrophil count (ANC) \<1.0 X 10\^9 cells/Liter (L) and fever ≥38.5°Celsius (C)).
* Neutropenia ≥ Grade 3 with documented infection.
* Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with bleeding.
* Thrombocytopenia of any Grade which requires platelet transfusions.
* Grade 4 anaemia unexplained by underlying disease.
* Anaemia of any Grade which requires blood transfusions.
Non-haematological toxicities:
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 times upper level of normal (ULN) and concurrent total bilirubin \>2 times ULN without initial findings of cholestasis.
* ≥Grade 4 AST or ALT of any duration.
* Any ≥Grade 3 non-haematologic toxicity some exceptions as defined in the protocol.Part A: Maximum Tolerated Dose (MTD) of BI 891065 First treatment cycle, 21 days from first administration of BI 891065. Maximum tolerated dose (MTD) of BI 891065 in the Part A of the trial is reported.
MTD was defined as the highest dose with less than 25% risk of the true DLT rate being equal or above 33% during the MTD evaluation period.Part A: Number of Patients With Dose Limiting Toxicities (DLTs) During the Treatment Period From first administration of BI 891065 until the last administration + 30 days of residual effect period, up to 1164 days. Any of the following adverse events (AEs) were classified as DLTs:
Haematologic toxicities:
* Any Grade 5 toxicity.
* Neutropenia ≥ Grade 4 lasting for \>7 days.
* Febrile neutropenia of any duration (absolute neutrophil count (ANC) \<1.0 X 10\^9 cells/Liter (L) and fever ≥38.5°Celsius (C)).
* Neutropenia ≥ Grade 3 with documented infection.
* Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with bleeding.
* Thrombocytopenia of any Grade which requires platelet transfusions.
* Grade 4 anaemia unexplained by underlying disease.
* Anaemia of any Grade which requires blood transfusions.
Non-haematological toxicities:
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 times upper level of normal (ULN) and concurrent total bilirubin \>2 times ULN without initial findings of cholestasis.
* ≥Grade 4 AST or ALT of any duration.
* Any ≥Grade 3 non-haematologic toxicity some exceptions as defined in the protocol.
- Secondary Outcome Measures
Name Time Method Maximum Measured Concentration in Plasma of BI 891065 After Administration of the First Dose (Cmax) Within 5 minutes before and 0.5 hours (h), 1h, 2h, 3h, 5h, 6h, 7h, 8h, 10h, 24h, 36h and 48h after first BI 891065 administration. Maximum measured concentration in plasma of BI 891065 after administration of the first dose (Cmax) is reported.
Part A: Maximum Measured Concentration in Plasma of BI 891065 at Steady State (Cmax,ss) Within 5 minutes before and 0.5 hours (h), 1h, 2h, 3h, 5h, 6h, 7h, 8h, 10h and 24 h after drug administration of BI 891065 on Day 15 of Cycle 1. Maximum measured concentration in plasma of BI 891065 at steady state (Cmax,ss) is reported.
Part A: Area Under the Concentration-time Curve of BI 891065 in Plasma 24 Hours After Administration of the First Dose (AUC0-24) Within 5 minutes before and 0.5 hours (h), 1h, 2h, 3h, 5h, 6h, 7h, 8h, 10h and 24h after first administration of BI 891065 on Day 1 of Cycle 1. Area under the concentration-time curve of BI 891065 in plasma 24 hours after administration of the first dose (AUC0-24) is reported.
Part A: Area Under the Concentration-time Curve of BI 891065 in Plasma Over a Uniform Dosing Interval τ at Steady State (AUCτ,ss) Within 5 minutes before and 0.5 hours (h), 1h, 2h, 3h, 5h, 6h, 7h, 8h, 10h and 24 h after drug administration of BI 891065 on Day 15 of Cycle 1. Area under the concentration-time curve of BI 891065 in plasma over a uniform dosing interval τ at steady state (AUCτ,ss) is reported. τ=24 hours (h) for the once daily dosing arms and τ=12 h for the twice daily dosing arm.
Trial Locations
- Locations (1)
National Cancer Center Hospital
🇯🇵Tokyo, Chuo-ku, Japan