Clinical trial NCT01938846: BI 860585 Dose Escalation Single Agent and in Combination With Exemestane or With Paclitaxel in Patients With Various Advanced and/or Metastatic Solid Tumors
Official title: An Open Label Phase I Dose Finding Study of BI 860585 Administered Orally in a Continuous Dosing Schedule as Single Agent and in Combination With Exemestane or With Paclitaxel in Patients With Various Advanced and/or Metastatic Solid Tumours
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2013-09-10
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: The Number of Patients With Dose-Limiting Toxicities (DLTs) in the First Course of Each Treatment Arm
timeFrame: 28 days (Maximum tolerated dose (MTD) evaluation period (First Treatment Cycle))
measure: The Maximum Tolerated Dose (MTD) for Each Treatment Arm
timeFrame: 28 days (Maximum tolerated dose (MTD) evaluation period (First Treatment Cycle))
Secondary outcomes:
measure: Objective Response Rate (Complete Response or Partial Response as Per the Response Evaluation Criteria In Solid Tumors Criteria [RECIST], Version 1.1)
timeFrame: 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
measure: 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)
timeFrame: From the date of first treatment administration until the earliest of disease progression, death, or last adequate tumour assessment before new anti-cancer therapy.
measure: Duration of Clinical Benefit
timeFrame: 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
measure: Duration of Objective Response
timeFrame: 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
measure: Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to Infinity (AUC0-∞)
timeFrame: 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.
measure: Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to 24 Hours (AUC0-24)
timeFrame: 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.
measure: Half Life of BI 860585 (t1/2)
timeFrame: 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.
measure: Maximum Measured Concentration of BI 860585 (Cmax)
timeFrame: 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.
measure: Time to Maximum Concentration of BI 860585 (Tmax)
timeFrame: 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.
measure: Area Under the Concentration-time Curve of BI 860585 in Plasma Over a Dosing Interval at Steady State (AUCτ,ss)
timeFrame: Pharmacokinetic samples were collected at pre-dose and at 504.5, 505, 506, 507, 508, 510, 512, 527.917 hours after drug administration.
measure: Half Life of BI 860585 at Steady State (t1/2,ss)
timeFrame: Pharmacokinetic samples were collected at pre-dose and at 504.5, 505, 506, 507, 508, 510, 512, 527.917 hours after drug administration.
measure: Time to Maximum Concentration of BI 860585 at Steady State (Tmax,ss)
timeFrame: Pharmacokinetic samples were collected at pre-dose and at 504.5, 505, 506, 507, 508, 510, 512, 527.917 hours after drug administration.
measure: Maximum Measured Concentration of BI 860585 in Plasma at Steady State (Cmax,ss)
timeFrame: Pharmacokinetic samples were collected at pre-dose and at 504.5, 505, 506, 507, 508, 510, 512, 527.917 hours after drug administration.
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Brussels - UNIV Saint-Luc
city: Gent
country: Belgium
facility: UNIV UZ Gent
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Parma
country: Italy
facility: Azienda Ospedaliera di Parma
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: