BI 860585 Dose Escalation Single Agent and in Combination With Exemestane or With Paclitaxel in Patients With Various Advanced and/or Metastatic Solid Tumors

Phase 1CompletedNCT01938846

Boehringer Ingelheim90 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Neoplasms

Interventions

BI 860585DRUG

BI 860585 multiple dose escalation, once daily

exemestaneDRUG

exemestane once daily

BI 860585DRUG

BI 860585 multiple dose escalation, once daily

BI 860585

Eligibility

Sex: ALLMin age: 18 YearsMax age: 99 Years

Medical Language ↔ Plain English

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.

Locations (4)

Brussels - UNIV Saint-Luc

Brussels, Belgium

UNIV UZ Gent

Ghent, Belgium

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy

Azienda Ospedaliera di Parma

Parma, Italy

Outcomes

Primary Outcomes

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))

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))

Secondary Outcomes

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

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)

Data from ClinicalTrials.gov

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