BI 860585 Dose Escalation Single Agent and in Combination With Exemestane or With Paclitaxel in Patients With Various Advanced and/or Metastatic Solid Tumors
- Registration Number
- NCT01938846
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
The primary objective of the trial is to determine the maximum tolerated doses (MTD) of BI 860585 alone and in combination with exemestane or paclitaxel. To determine the MTDs, patients are entered sequentially into escalating dose cohorts. Secondary objectives are objective response and disease control according to RECIST criteria version 1.1
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 90
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BI 860585 BI 860585 Multiple ascending doses of BI 860585 administered continuously in a 28-day cycle, including food interaction cohorts BI 860585 + paclitaxel paclitaxel Multiple ascending doses of BI 860585 in combination with fixed dose paclitaxel BI 860585 + exemestane BI 860585 Multiple ascending doses of BI 860585 in combination with fixed dose exemestane BI 860585 + paclitaxel BI 860585 Multiple ascending doses of BI 860585 in combination with fixed dose paclitaxel BI 860585 + exemestane exemestane Multiple ascending doses of BI 860585 in combination with fixed dose exemestane
- Primary Outcome Measures
Name Time Method The Maximum Tolerated Dose (MTD) for Each Treatment Arm 28 days (Maximum tolerated dose (MTD) evaluation period (First Treatment Cycle)) The Maximum Tolerated Dose (MTD) for each treatment arm was the dose that was 1 dose cohort below that at which ≥2 of 6 patients had experienced DLT. i.e., the MTD was the highest dose studied for which the DLT incidence was no more than 17% (i.e. 1 of 6 patients) during the first treatment course.
The Number of Patients With Dose-Limiting Toxicities (DLTs) in the First Course of Each Treatment Arm 28 days (Maximum tolerated dose (MTD) evaluation period (First Treatment Cycle)) The number of patients with Dose-Limiting Toxicities (DLTs) in the first course of each treatment arm to identify the Maximum Tolerated Dose (MTD) for BI 860585 monotherapy and BI 860585 in combination with exemestane of paclitaxel.
- Secondary Outcome Measures
Name Time Method Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to 24 Hours (AUC0-24) Pharmacokinetic samples were collected at pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 23.917 hours after administration of BI 860585. AUC0-24, area under the concentration-time curve in plasma of BI 860585 over the time interval from 0 to 24 hours after single administration of BI 860585
Objective Response Rate (Complete Response or Partial Response as Per the Response Evaluation Criteria In Solid Tumors Criteria [RECIST], Version 1.1) From the date of first treatment administration until the earliest of disease progression, death, or last adequate tumour assessment before new anti-cancer therapy; data collected up to cut-off date 30 Jun 2017, Up to 1389 days As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for objective response rate (Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions) for target lesions assessed by Magnetic resonance imaging (MRI) and Computed tomography (CT)
Disease Control Rate/Clinical Benefit Rate (Complete Response, Partial Response or Stable Disease as Per Response Evaluation Criteria In Solid Tumors Criteria [RECIST], Version 1.1) From the date of first treatment administration until the earliest of disease progression, death, or last adequate tumour assessment before new anti-cancer therapy. As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for disease control rate/clinical benefit rate (Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression) for target lesions assessed by Magnetic resonance imaging (MRI) and Computed tomography (CT)
Half Life of BI 860585 (t1/2) Pharmacokinetic samples were collected at pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 23.917 hours after administration of BI 860585. t ½, half-life of BI 860585 in plasma over a dosing interval after single administration of BI 860585
Maximum Measured Concentration of BI 860585 (Cmax) Pharmacokinetic samples were collected at pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 23.917 hours after administration of BI 860585. Cmax, maximum measured concentration of BI 860585 in plasma over a dosing interval after single administration of BI 860585
Time to Maximum Concentration of BI 860585 (Tmax) Pharmacokinetic samples were collected at pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 23.917 hours after administration of BI 860585. Tmax, Time to maximum concentration of BI 860585 in plasma over a dosing interval after single administration of BI 860585
Half Life of BI 860585 at Steady State (t1/2,ss) Pharmacokinetic samples were collected at pre-dose and at 504.5, 505, 506, 507, 508, 510, 512, 527.917 hours after drug administration. t1/2,ss, half-life of BI 860585 in plasma at steady state after multiple administration of BI 860585 (Day 22) in BI 860585 monotherapy and in combination with exemestane and paclitaxel.
Duration of Clinical Benefit From the date of first treatment administration until the earliest of disease progression, death, or last adequate tumour assessment before new anti-cancer therapy; data collected up to cut-off date 30 Jun 2017, Up to 1389 days Duration of clinical benefit (Disease control) was defined as the time between first treatment administration until the earliest of disease progression or death, for patients with disease control.
Duration of Objective Response From the date of first treatment administration until the earliest of disease progression, death, or last adequate tumour assessment before new anti-cancer therapy; data collected up to cut-off date 30 Jun 2017, Up to 1389 days Duration of objective response was defined as the time from first objective response until the earliest of progression or death, for patients with objective response.
Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to Infinity (AUC0-∞) Pharmacokinetic samples were collected at pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 23.917 hours after administration of BI 860585. AUC0-∞, area under the concentration-time curve in plasma of BI 860585 over the time interval from 0 to infinity after single administration of BI 860585
Maximum Measured Concentration of BI 860585 in Plasma at Steady State (Cmax,ss) Pharmacokinetic samples were collected at pre-dose and at 504.5, 505, 506, 507, 508, 510, 512, 527.917 hours after drug administration. Cmax,ss, maximum measured concentration at steady state after multiple administration of BI 860585 (Day 22) in BI 860585 monotherapy and in combination with exemestane and paclitaxel.
Area Under the Concentration-time Curve of BI 860585 in Plasma Over a Dosing Interval at Steady State (AUCτ,ss) Pharmacokinetic samples were collected at pre-dose and at 504.5, 505, 506, 507, 508, 510, 512, 527.917 hours after drug administration. AUCτ,ss, area under the concentration-time curve of BI 860585 in plasma over the dosing interval at steady state after multiple administration of BI 860585 (Day 22) in BI 860585 monotherapy and in combination with exemestane and paclitaxel.
Time to Maximum Concentration of BI 860585 at Steady State (Tmax,ss) Pharmacokinetic samples were collected at pre-dose and at 504.5, 505, 506, 507, 508, 510, 512, 527.917 hours after drug administration. tmax,ss, Time to maximum concentration of BI 860585 at steady state after multiple administration of BI 860585 (Day 22) in BI 860585 monotherapy and in combination with exemestane and paclitaxel.
Trial Locations
- Locations (4)
UNIV UZ Gent
🇧🇪Gent, Belgium
Brussels - UNIV Saint-Luc
🇧🇪Bruxelles, Belgium
Azienda Ospedaliera di Parma
🇮🇹Parma, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy