Neoplasms
Conditions
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
Interventions
DRUGBI 860585
BI 860585 multiple dose escalation, once daily
DRUGexemestane
exemestane once daily
DRUGpaclitaxel
paclitaxel once weekly
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Patients with histologically or cytologically confirmed diagnosis of advanced, measurable or evaluable, non-resectable and/or metastatic solid tumours, which has shown to be progressive; * Patients who have received previous standard of care therapy for their disease and have progressed; * 18 years or older; * Life expectancy \>= 3 months; * Written informed consent in accordance with International Conference on Harmonisation/Good Clinical Practice (ICH/GCP) and local legislation; * Eastern Cooperative Oncology Group (ECOG), performance score 0-2. Additional inclusion criteria for the combination arms: * Patients must have confirmed progressive disease within the last 6 months, (in case of measurable disease, progression should be confirmed according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria version 1.1; * Patients carrying a tumour for whom treatment with either exemestane or paclitaxel would be considered appropriate by the investigator; Additional inclusion criteria for expansion part: * Patients must have measurable progressive disease within the last 6 months documented/proven according to RECIST criteria version 1.1. * Patients entering the expansion cohorts must also have: * Arm A: any advanced/metastatic solid tumour suitable for biopsy and must have provided informed consent for biopsy and biomarker analysis. * Arm B: any cytologically or histologically confirmed ER+ (estrogen receptor positive) advanced/metastatic solid tumours for which treatment with exemestane would be considered appropriate by the investigator. * Arm C: any advanced/metastatic solid tumour for which treatment with paclitaxel would be considered appropriate by the investigator.
Exclusion criteria
* Serious concomitant non-oncological disease/illness considered by the investigator to be incompatible with the protocol; * Patients with untreated or symptomatic brain metastases; * Second malignancies requiring active therapy; * Clinical Congestive Heart Failure (CHF) Grade III-IV; * Myocardial infarction within the last 6 months prior to inclusion, or symptomatic coronary artery disease; * Adequate bone marrow, liver and renal function; * Patients with known HIV/hepatitis/active infectious disease considered by the investigator to be incompatible with the protocol; * Patients unable to take oral medication; * Chronic diarrhoea or other gastrointestinal disorders; * Treatment with anti-cancer-therapies: cytotoxic or standard chemotherapy, immunotherapy, radiotherapy, biological therapies, molecular targeted or other investigational drugs, within four weeks of the first treatment with the study medication (or within one week for non-cytotoxic drugs); * Recovery from previous surgery and anticancer medical treatments; * Hypersensitivity to combination drugs or excipients; * Patients with a history of uncontrolled diabetes mellitus.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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) |
| 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 |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 |
| 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) |
Countries
Belgium, Italy
Participant flow
Recruitment details
An open-label, Phase I, dose-finding study of BI 860585, a total of 90 patients received at least one dose of study medication.
Pre-assignment details
All patients were screened for eligibility to participate in the trial. Patients attended specialist sites which would then ensure that all patients met all inclusion/exclusion criteria. Patients were not to be entered to trial treatment if any one of the specific entry criteria were not met.
Participants by arm
| Arm | Count |
|---|---|
| BI 860585 Monotherapy Patients were administered with BI 860585 daily oral dose of 5 milligram starting dose) over 28-day treatment courses | 41 |
| BI 860585 + Exemestane Patients were administered with daily oral dose of BI 860585 in combination with 25 milligram/day standard fixed dose of Exemestane over 28-day treatment courses | 25 |
| BI 860585 + Paclitaxel Patients were administered with BI 860585 in combination with Paclitaxel weekly intravenous infusion of 60 milligram/meter\^2 for the first dose level/treatment cohort and 80 milligram/meter\^2 (the standard combination dose) for subsequent dose levels/treatment cohorts over 28-day treatment courses | 24 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 8 | 4 | 3 |
| Overall Study | Other than listed | 5 | 1 | 4 |
| Overall Study | Progressive disease | 26 | 18 | 16 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 1 |
Baseline characteristics
| Characteristic | BI 860585 Monotherapy | BI 860585 + Exemestane | BI 860585 + Paclitaxel | Total |
|---|---|---|---|---|
| Age, Continuous | 58.4 Years STANDARD_DEVIATION 13.8 | 58.3 Years STANDARD_DEVIATION 9.5 | 58.5 Years STANDARD_DEVIATION 10.2 | 58.4 Years STANDARD_DEVIATION 11.7 |
| Sex: Female, Male Female | 13 Participants | 23 Participants | 12 Participants | 48 Participants |
| Sex: Female, Male Male | 28 Participants | 2 Participants | 12 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 1 / 3 | 1 / 3 | 0 / 3 | 0 / 3 | 1 / 7 | 1 / 7 | 0 / 9 | 0 / 3 | 0 / 3 | 3 / 4 | 1 / 7 | 0 / 8 | 0 / 3 | 0 / 3 | 0 / 4 | 0 / 7 | 0 / 7 | 0 / 3 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 7 / 7 | 7 / 7 | 9 / 9 | 3 / 3 | 3 / 3 | 4 / 4 | 7 / 7 | 8 / 8 | 3 / 3 | 3 / 3 | 4 / 4 | 7 / 7 | 7 / 7 | 3 / 3 |
| serious Total, serious adverse events | 2 / 3 | 1 / 3 | 2 / 3 | 1 / 3 | 2 / 3 | 4 / 7 | 4 / 7 | 4 / 9 | 2 / 3 | 0 / 3 | 4 / 4 | 3 / 7 | 2 / 8 | 1 / 3 | 2 / 3 | 3 / 4 | 3 / 7 | 4 / 7 | 1 / 3 |
Outcome results
Primary
The Maximum Tolerated Dose (MTD) for Each Treatment Arm
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.
Time frame: 28 days (Maximum tolerated dose (MTD) evaluation period (First Treatment Cycle))
Population: Treated and Evaluable Set: The treated and evaluable set includes all patients who were administered at least one dose of study medication and who are evaluable with respect to DLT in the MTD evaluation period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BI 860585 Monotherapy | The Maximum Tolerated Dose (MTD) for Each Treatment Arm | Exemestane | NA Milligram (mg) |
| BI 860585 Monotherapy | The Maximum Tolerated Dose (MTD) for Each Treatment Arm | BI 860585 | 220 Milligram (mg) |
| BI 860585 Monotherapy | The Maximum Tolerated Dose (MTD) for Each Treatment Arm | Paclitaxel | NA Milligram (mg) |
| BI 860585 + Exemestane | The Maximum Tolerated Dose (MTD) for Each Treatment Arm | Exemestane | 25 Milligram (mg) |
| BI 860585 + Exemestane | The Maximum Tolerated Dose (MTD) for Each Treatment Arm | BI 860585 | 160 Milligram (mg) |
| BI 860585 + Exemestane | The Maximum Tolerated Dose (MTD) for Each Treatment Arm | Paclitaxel | NA Milligram (mg) |
| BI 860585 + Paclitaxel | The Maximum Tolerated Dose (MTD) for Each Treatment Arm | BI 860585 | 160 Milligram (mg) |
| BI 860585 + Paclitaxel | The Maximum Tolerated Dose (MTD) for Each Treatment Arm | Paclitaxel | 80 Milligram (mg) |
| BI 860585 + Paclitaxel | The Maximum Tolerated Dose (MTD) for Each Treatment Arm | Exemestane | NA Milligram (mg) |
Primary
The Number of Patients With Dose-Limiting Toxicities (DLTs) in the First Course of Each Treatment Arm
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.
Time frame: 28 days (Maximum tolerated dose (MTD) evaluation period (First Treatment Cycle))
Population: Treated and Evaluable Set: The treated and evaluable set includes all patients who were administered at least one dose of study medication and who are evaluable with respect to DLT in the MTD evaluation period.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BI 860585 Monotherapy | The Number of Patients With Dose-Limiting Toxicities (DLTs) in the First Course of Each Treatment Arm | Total with dose limiting toxicities | 4 Participants |
| BI 860585 + Exemestane | The Number of Patients With Dose-Limiting Toxicities (DLTs) in the First Course of Each Treatment Arm | Total with dose limiting toxicities | 4 Participants |
| BI 860585 + Paclitaxel | The Number of Patients With Dose-Limiting Toxicities (DLTs) in the First Course of Each Treatment Arm | Total with dose limiting toxicities | 2 Participants |
Secondary
Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to 24 Hours (AUC0-24)
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
Time frame: 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.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 860585 Monotherapy | Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to 24 Hours (AUC0-24) | 12900 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 20 |
| BI 860585 + Exemestane | Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to 24 Hours (AUC0-24) | 23400 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 30.7 |
| BI 860585 + Paclitaxel | Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to 24 Hours (AUC0-24) | 45400 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 29.6 |
| 40 mg BI 860585 | Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to 24 Hours (AUC0-24) | 83200 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 24.7 |
| 80 mg BI 860585 | Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to 24 Hours (AUC0-24) | 236000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 15.6 |
| 120 mg BI 860585 | Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to 24 Hours (AUC0-24) | 299000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 21.1 |
| 160 mg BI 860585 | Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to 24 Hours (AUC0-24) | 401000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 21.4 |
| 220 mg BI 860585 | Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to 24 Hours (AUC0-24) | 470000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 6.09 |
| 300 mg BI 860585 | Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to 24 Hours (AUC0-24) | 641000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 8.43 |
Secondary
Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to Infinity (AUC0-∞)
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
Time frame: 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.
Population: Pharmacokinetic Analysis Set (PKS): This patient set includes all evaluable patients in the treated set (TS) which provide at least one observation for at least one pharmacokinetic (PK) endpoint without important protocol violations relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 860585 Monotherapy | Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to Infinity (AUC0-∞) | 21100 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 27.3 |
| BI 860585 + Exemestane | Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to Infinity (AUC0-∞) | 51100 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 65.4 |
| BI 860585 + Paclitaxel | Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to Infinity (AUC0-∞) | 70300 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 26.4 |
| 40 mg BI 860585 | Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to Infinity (AUC0-∞) | 126000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 17.7 |
| 80 mg BI 860585 | Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to Infinity (AUC0-∞) | 425000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 28.5 |
| 160 mg BI 860585 | Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to Infinity (AUC0-∞) | 680000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 38.9 |
| 220 mg BI 860585 | Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to Infinity (AUC0-∞) | 791000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 12.3 |
| 300 mg BI 860585 | Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to Infinity (AUC0-∞) | 1030000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 10.5 |
Secondary
Area Under the Concentration-time Curve of BI 860585 in Plasma Over a Dosing Interval at Steady State (AUCτ,ss)
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 frame: Pharmacokinetic samples were collected at pre-dose and at 504.5, 505, 506, 507, 508, 510, 512, 527.917 hours after drug administration.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 860585 Monotherapy | Area Under the Concentration-time Curve of BI 860585 in Plasma Over a Dosing Interval at Steady State (AUCτ,ss) | 32000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 9.28 |
| BI 860585 + Exemestane | Area Under the Concentration-time Curve of BI 860585 in Plasma Over a Dosing Interval at Steady State (AUCτ,ss) | 63100 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 86.1 |
| BI 860585 + Paclitaxel | Area Under the Concentration-time Curve of BI 860585 in Plasma Over a Dosing Interval at Steady State (AUCτ,ss) | 103000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 3.91 |
| 40 mg BI 860585 | Area Under the Concentration-time Curve of BI 860585 in Plasma Over a Dosing Interval at Steady State (AUCτ,ss) | 163000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 6.34 |
| 80 mg BI 860585 | Area Under the Concentration-time Curve of BI 860585 in Plasma Over a Dosing Interval at Steady State (AUCτ,ss) | 442000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 21.8 |
| 160 mg BI 860585 | Area Under the Concentration-time Curve of BI 860585 in Plasma Over a Dosing Interval at Steady State (AUCτ,ss) | 840000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 23.9 |
| 220 mg BI 860585 | Area Under the Concentration-time Curve of BI 860585 in Plasma Over a Dosing Interval at Steady State (AUCτ,ss) | 838000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 24.3 |
| 300 mg BI 860585 | Area Under the Concentration-time Curve of BI 860585 in Plasma Over a Dosing Interval at Steady State (AUCτ,ss) | 1350000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 12.3 |
| 40 mg BI 860585+25 mg Exemestane | Area Under the Concentration-time Curve of BI 860585 in Plasma Over a Dosing Interval at Steady State (AUCτ,ss) | 271000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 12.9 |
| 80 mg BI 860585+25 mg Exemestane | Area Under the Concentration-time Curve of BI 860585 in Plasma Over a Dosing Interval at Steady State (AUCτ,ss) | 281000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 31.8 |
| 120 mg BI 860585+25 mg Exemestane | Area Under the Concentration-time Curve of BI 860585 in Plasma Over a Dosing Interval at Steady State (AUCτ,ss) | 676000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 30.7 |
| 160 mg BI 860585+25 mg Exemestane | Area Under the Concentration-time Curve of BI 860585 in Plasma Over a Dosing Interval at Steady State (AUCτ,ss) | 988000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 19.1 |
| 80 mg BI 860585+60 mg/m^2 Paclitaxel | Area Under the Concentration-time Curve of BI 860585 in Plasma Over a Dosing Interval at Steady State (AUCτ,ss) | 374000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 4.69 |
| 120 mg BI 860585+80 mg/m^2 Paclitaxel | Area Under the Concentration-time Curve of BI 860585 in Plasma Over a Dosing Interval at Steady State (AUCτ,ss) | 630000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 54.8 |
| 160 mg BI 860585+80 mg/m^2 Paclita | Area Under the Concentration-time Curve of BI 860585 in Plasma Over a Dosing Interval at Steady State (AUCτ,ss) | 730000 nanomol*hour/ Litre [nmol*h/L] | Geometric Coefficient of Variation 20.3 |
Secondary
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)
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)
Time frame: From the date of first treatment administration until the earliest of disease progression, death, or last adequate tumour assessment before new anti-cancer therapy.
Population: Treated Set: The treated set includes all patients who were administered at least one dose of any study medication (BI 860585, exemestane or paclitaxel).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BI 860585 Monotherapy | 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) | 8 Participants |
| BI 860585 + Exemestane | 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) | 7 Participants |
| BI 860585 + Paclitaxel | 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) | 14 Participants |
Secondary
Duration of Clinical Benefit
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.
Time frame: 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
Population: Patients with disease control from the treated set (Treated Set: The treated set includes all patients who were administered at least one dose of any study medication (BI 860585, exemestane or paclitaxel)).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BI 860585 Monotherapy | Duration of Clinical Benefit | 8.31 Months | Standard Deviation 4.78 |
| BI 860585 + Exemestane | Duration of Clinical Benefit | 10.06 Months | Standard Deviation 7.26 |
| BI 860585 + Paclitaxel | Duration of Clinical Benefit | 7.79 Months | Standard Deviation 3.3 |
Secondary
Duration of Objective Response
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.
Time frame: 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
Population: Patients with objective response from the treated set (Treated Set: The treated set includes all patients who were administered at least one dose of any study medication (BI 860585, exemestane or paclitaxel)).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BI 860585 + Exemestane | Duration of Objective Response | 9.16 Months | Standard Deviation 9.83 |
| BI 860585 + Paclitaxel | Duration of Objective Response | 4.42 Months | Standard Deviation 3.06 |
Secondary
Half Life of BI 860585 at Steady State (t1/2,ss)
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.
Time frame: Pharmacokinetic samples were collected at pre-dose and at 504.5, 505, 506, 507, 508, 510, 512, 527.917 hours after drug administration.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 860585 Monotherapy | Half Life of BI 860585 at Steady State (t1/2,ss) | 31.5 Hour (h) | Geometric Coefficient of Variation 8.73 |
| BI 860585 + Exemestane | Half Life of BI 860585 at Steady State (t1/2,ss) | 28.9 Hour (h) | Geometric Coefficient of Variation 47.4 |
| BI 860585 + Paclitaxel | Half Life of BI 860585 at Steady State (t1/2,ss) | 33.1 Hour (h) | Geometric Coefficient of Variation 10.2 |
| 40 mg BI 860585 | Half Life of BI 860585 at Steady State (t1/2,ss) | 21.3 Hour (h) | Geometric Coefficient of Variation 20 |
| 80 mg BI 860585 | Half Life of BI 860585 at Steady State (t1/2,ss) | 29.8 Hour (h) | Geometric Coefficient of Variation 7.67 |
| 160 mg BI 860585 | Half Life of BI 860585 at Steady State (t1/2,ss) | 27.6 Hour (h) | Geometric Coefficient of Variation 18.3 |
| 220 mg BI 860585 | Half Life of BI 860585 at Steady State (t1/2,ss) | 24.9 Hour (h) | Geometric Coefficient of Variation 22.2 |
| 40 mg BI 860585+25 mg Exemestane | Half Life of BI 860585 at Steady State (t1/2,ss) | 22.9 Hour (h) | Geometric Coefficient of Variation 13.8 |
| 80 mg BI 860585+25 mg Exemestane | Half Life of BI 860585 at Steady State (t1/2,ss) | 24.7 Hour (h) | Geometric Coefficient of Variation 68.4 |
| 120 mg BI 860585+25 mg Exemestane | Half Life of BI 860585 at Steady State (t1/2,ss) | 23.3 Hour (h) | Geometric Coefficient of Variation 7.82 |
| 160 mg BI 860585+25 mg Exemestane | Half Life of BI 860585 at Steady State (t1/2,ss) | 25.3 Hour (h) | Geometric Coefficient of Variation 25.9 |
| 120 mg BI 860585+80 mg/m^2 Paclitaxel | Half Life of BI 860585 at Steady State (t1/2,ss) | 24.2 Hour (h) | Geometric Coefficient of Variation 37.2 |
Secondary
Half Life of BI 860585 (t1/2)
t ½, half-life of BI 860585 in plasma over a dosing interval after single administration of BI 860585
Time frame: 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.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 860585 Monotherapy | Half Life of BI 860585 (t1/2) | 17.1 Hour (h) | Geometric Coefficient of Variation 14.5 |
| BI 860585 + Exemestane | Half Life of BI 860585 (t1/2) | 21.6 Hour (h) | Geometric Coefficient of Variation 50.1 |
| BI 860585 + Paclitaxel | Half Life of BI 860585 (t1/2) | 15.6 Hour (h) | Geometric Coefficient of Variation 11.8 |
| 40 mg BI 860585 | Half Life of BI 860585 (t1/2) | 14.2 Hour (h) | Geometric Coefficient of Variation 27.2 |
| 80 mg BI 860585 | Half Life of BI 860585 (t1/2) | 19.7 Hour (h) | Geometric Coefficient of Variation 28 |
| 160 mg BI 860585 | Half Life of BI 860585 (t1/2) | 17.2 Hour (h) | Geometric Coefficient of Variation 33.7 |
| 220 mg BI 860585 | Half Life of BI 860585 (t1/2) | 17.4 Hour (h) | Geometric Coefficient of Variation 11 |
| 300 mg BI 860585 | Half Life of BI 860585 (t1/2) | 16.9 Hour (h) | Geometric Coefficient of Variation 6.14 |
Secondary
Maximum Measured Concentration of BI 860585 (Cmax)
Cmax, maximum measured concentration of BI 860585 in plasma over a dosing interval after single administration of BI 860585
Time frame: 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.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 860585 Monotherapy | Maximum Measured Concentration of BI 860585 (Cmax) | 995 nanomole/Litre [nmol/L] | Geometric Coefficient of Variation 26.3 |
| BI 860585 + Exemestane | Maximum Measured Concentration of BI 860585 (Cmax) | 1590 nanomole/Litre [nmol/L] | Geometric Coefficient of Variation 21.5 |
| BI 860585 + Paclitaxel | Maximum Measured Concentration of BI 860585 (Cmax) | 3330 nanomole/Litre [nmol/L] | Geometric Coefficient of Variation 4.76 |
| 40 mg BI 860585 | Maximum Measured Concentration of BI 860585 (Cmax) | 6770 nanomole/Litre [nmol/L] | Geometric Coefficient of Variation 37.6 |
| 80 mg BI 860585 | Maximum Measured Concentration of BI 860585 (Cmax) | 16900 nanomole/Litre [nmol/L] | Geometric Coefficient of Variation 15 |
| 120 mg BI 860585 | Maximum Measured Concentration of BI 860585 (Cmax) | 18800 nanomole/Litre [nmol/L] | Geometric Coefficient of Variation 16.4 |
| 160 mg BI 860585 | Maximum Measured Concentration of BI 860585 (Cmax) | 28000 nanomole/Litre [nmol/L] | Geometric Coefficient of Variation 36 |
| 220 mg BI 860585 | Maximum Measured Concentration of BI 860585 (Cmax) | 32400 nanomole/Litre [nmol/L] | Geometric Coefficient of Variation 18.5 |
| 300 mg BI 860585 | Maximum Measured Concentration of BI 860585 (Cmax) | 51500 nanomole/Litre [nmol/L] | Geometric Coefficient of Variation 10.7 |
Secondary
Maximum Measured Concentration of BI 860585 in Plasma at Steady State (Cmax,ss)
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.
Time frame: Pharmacokinetic samples were collected at pre-dose and at 504.5, 505, 506, 507, 508, 510, 512, 527.917 hours after drug administration.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 860585 Monotherapy | Maximum Measured Concentration of BI 860585 in Plasma at Steady State (Cmax,ss) | 1730 nanomol/ Litre [nmol/L] | Geometric Coefficient of Variation 18.5 |
| BI 860585 + Exemestane | Maximum Measured Concentration of BI 860585 in Plasma at Steady State (Cmax,ss) | 3720 nanomol/ Litre [nmol/L] | Geometric Coefficient of Variation 47 |
| BI 860585 + Paclitaxel | Maximum Measured Concentration of BI 860585 in Plasma at Steady State (Cmax,ss) | 6630 nanomol/ Litre [nmol/L] | Geometric Coefficient of Variation 0.832 |
| 40 mg BI 860585 | Maximum Measured Concentration of BI 860585 in Plasma at Steady State (Cmax,ss) | 11600 nanomol/ Litre [nmol/L] | Geometric Coefficient of Variation 21.5 |
| 80 mg BI 860585 | Maximum Measured Concentration of BI 860585 in Plasma at Steady State (Cmax,ss) | 29700 nanomol/ Litre [nmol/L] | Geometric Coefficient of Variation 28.2 |
| 120 mg BI 860585 | Maximum Measured Concentration of BI 860585 in Plasma at Steady State (Cmax,ss) | 33700 nanomol/ Litre [nmol/L] | Geometric Coefficient of Variation 26.6 |
| 160 mg BI 860585 | Maximum Measured Concentration of BI 860585 in Plasma at Steady State (Cmax,ss) | 50100 nanomol/ Litre [nmol/L] | Geometric Coefficient of Variation 16.7 |
| 220 mg BI 860585 | Maximum Measured Concentration of BI 860585 in Plasma at Steady State (Cmax,ss) | 50500 nanomol/ Litre [nmol/L] | Geometric Coefficient of Variation 27.1 |
| 300 mg BI 860585 | Maximum Measured Concentration of BI 860585 in Plasma at Steady State (Cmax,ss) | 75700 nanomol/ Litre [nmol/L] | Geometric Coefficient of Variation 17.5 |
| 40 mg BI 860585+25 mg Exemestane | Maximum Measured Concentration of BI 860585 in Plasma at Steady State (Cmax,ss) | 16700 nanomol/ Litre [nmol/L] | Geometric Coefficient of Variation 3.63 |
| 80 mg BI 860585+25 mg Exemestane | Maximum Measured Concentration of BI 860585 in Plasma at Steady State (Cmax,ss) | 19600 nanomol/ Litre [nmol/L] | Geometric Coefficient of Variation 31.2 |
| 120 mg BI 860585+25 mg Exemestane | Maximum Measured Concentration of BI 860585 in Plasma at Steady State (Cmax,ss) | 43800 nanomol/ Litre [nmol/L] | Geometric Coefficient of Variation 30.5 |
| 160 mg BI 860585+25 mg Exemestane | Maximum Measured Concentration of BI 860585 in Plasma at Steady State (Cmax,ss) | 61400 nanomol/ Litre [nmol/L] | Geometric Coefficient of Variation 25.7 |
| 80 mg BI 860585+60 mg/m^2 Paclitaxel | Maximum Measured Concentration of BI 860585 in Plasma at Steady State (Cmax,ss) | 20500 nanomol/ Litre [nmol/L] | Geometric Coefficient of Variation 13.8 |
| 80 mg BI 860585+80 mg/m^2 Paclitaxel | Maximum Measured Concentration of BI 860585 in Plasma at Steady State (Cmax,ss) | 20700 nanomol/ Litre [nmol/L] | Geometric Coefficient of Variation 39.6 |
| 120 mg BI 860585+80 mg/m^2 Paclitaxel | Maximum Measured Concentration of BI 860585 in Plasma at Steady State (Cmax,ss) | 38900 nanomol/ Litre [nmol/L] | Geometric Coefficient of Variation 56.4 |
| 160 mg BI 860585+80 mg/m^2 Paclita | Maximum Measured Concentration of BI 860585 in Plasma at Steady State (Cmax,ss) | 35400 nanomol/ Litre [nmol/L] | Geometric Coefficient of Variation 40.7 |
Secondary
Objective Response Rate (Complete Response or Partial Response as Per the Response Evaluation Criteria In Solid Tumors Criteria [RECIST], Version 1.1)
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)
Time frame: 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
Population: Treated Set: The treated set includes all patients who were administered at least one dose of any study medication (BI 860585, exemestane or paclitaxel).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BI 860585 Monotherapy | Objective Response Rate (Complete Response or Partial Response as Per the Response Evaluation Criteria In Solid Tumors Criteria [RECIST], Version 1.1) | 0 Participants |
| BI 860585 + Exemestane | Objective Response Rate (Complete Response or Partial Response as Per the Response Evaluation Criteria In Solid Tumors Criteria [RECIST], Version 1.1) | 4 Participants |
| BI 860585 + Paclitaxel | Objective Response Rate (Complete Response or Partial Response as Per the Response Evaluation Criteria In Solid Tumors Criteria [RECIST], Version 1.1) | 5 Participants |
Secondary
Time to Maximum Concentration of BI 860585 at Steady State (Tmax,ss)
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.
Time frame: Pharmacokinetic samples were collected at pre-dose and at 504.5, 505, 506, 507, 508, 510, 512, 527.917 hours after drug administration.
Population: PKS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BI 860585 Monotherapy | Time to Maximum Concentration of BI 860585 at Steady State (Tmax,ss) | 6.00 Hour (h) |
| BI 860585 + Exemestane | Time to Maximum Concentration of BI 860585 at Steady State (Tmax,ss) | 2.02 Hour (h) |
| BI 860585 + Paclitaxel | Time to Maximum Concentration of BI 860585 at Steady State (Tmax,ss) | 2.00 Hour (h) |
| 40 mg BI 860585 | Time to Maximum Concentration of BI 860585 at Steady State (Tmax,ss) | 3.00 Hour (h) |
| 80 mg BI 860585 | Time to Maximum Concentration of BI 860585 at Steady State (Tmax,ss) | 2.00 Hour (h) |
| 120 mg BI 860585 | Time to Maximum Concentration of BI 860585 at Steady State (Tmax,ss) | 3.61 Hour (h) |
| 160 mg BI 860585 | Time to Maximum Concentration of BI 860585 at Steady State (Tmax,ss) | 3.10 Hour (h) |
| 220 mg BI 860585 | Time to Maximum Concentration of BI 860585 at Steady State (Tmax,ss) | 3.03 Hour (h) |
| 300 mg BI 860585 | Time to Maximum Concentration of BI 860585 at Steady State (Tmax,ss) | 5.00 Hour (h) |
| 40 mg BI 860585+25 mg Exemestane | Time to Maximum Concentration of BI 860585 at Steady State (Tmax,ss) | 3.98 Hour (h) |
| 80 mg BI 860585+25 mg Exemestane | Time to Maximum Concentration of BI 860585 at Steady State (Tmax,ss) | 2.00 Hour (h) |
| 120 mg BI 860585+25 mg Exemestane | Time to Maximum Concentration of BI 860585 at Steady State (Tmax,ss) | 3.00 Hour (h) |
| 160 mg BI 860585+25 mg Exemestane | Time to Maximum Concentration of BI 860585 at Steady State (Tmax,ss) | 2.02 Hour (h) |
| 80 mg BI 860585+60 mg/m^2 Paclitaxel | Time to Maximum Concentration of BI 860585 at Steady State (Tmax,ss) | 2.03 Hour (h) |
| 80 mg BI 860585+80 mg/m^2 Paclitaxel | Time to Maximum Concentration of BI 860585 at Steady State (Tmax,ss) | 4.92 Hour (h) |
| 120 mg BI 860585+80 mg/m^2 Paclitaxel | Time to Maximum Concentration of BI 860585 at Steady State (Tmax,ss) | 2.50 Hour (h) |
| 160 mg BI 860585+80 mg/m^2 Paclita | Time to Maximum Concentration of BI 860585 at Steady State (Tmax,ss) | 6.00 Hour (h) |
Secondary
Time to Maximum Concentration of BI 860585 (Tmax)
Tmax, Time to maximum concentration of BI 860585 in plasma over a dosing interval after single administration of BI 860585
Time frame: 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.
Population: PKS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BI 860585 Monotherapy | Time to Maximum Concentration of BI 860585 (Tmax) | 3.03 Hour (h) |
| BI 860585 + Exemestane | Time to Maximum Concentration of BI 860585 (Tmax) | 4.00 Hour (h) |
| BI 860585 + Paclitaxel | Time to Maximum Concentration of BI 860585 (Tmax) | 3.00 Hour (h) |
| 40 mg BI 860585 | Time to Maximum Concentration of BI 860585 (Tmax) | 2.00 Hour (h) |
| 80 mg BI 860585 | Time to Maximum Concentration of BI 860585 (Tmax) | 3.00 Hour (h) |
| 120 mg BI 860585 | Time to Maximum Concentration of BI 860585 (Tmax) | 6.00 Hour (h) |
| 160 mg BI 860585 | Time to Maximum Concentration of BI 860585 (Tmax) | 3.47 Hour (h) |
| 220 mg BI 860585 | Time to Maximum Concentration of BI 860585 (Tmax) | 3.00 Hour (h) |
| 300 mg BI 860585 | Time to Maximum Concentration of BI 860585 (Tmax) | 2.00 Hour (h) |