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

NCT01938846 | Completed Phase 1 Results

• 2 other identifiers: 1325.12013-000765-36
• Study Type: interventional
• Target: 90
• Locations: 2 countries
• Sites: 4

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

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  28 days (Maximum tolerated dose (MTD) evaluation period (First Treatment Cycle))

Secondary Outcomes (13)

• 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

• 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.

• 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 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

• 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.

Study Arms (3)

BI 860585

EXPERIMENTAL

Multiple ascending doses of BI 860585 administered continuously in a 28-day cycle, including food interaction cohorts

Drug: BI 860585

BI 860585 + paclitaxel

EXPERIMENTAL

Multiple ascending doses of BI 860585 in combination with fixed dose paclitaxel

Drug: BI 860585; Drug: paclitaxel

BI 860585 + exemestane

EXPERIMENTAL

Multiple ascending doses of BI 860585 in combination with fixed dose exemestane

Drug: exemestane; Drug: BI 860585

Interventions

BI 860585 DRUG

BI 860585 multiple dose escalation, once daily

BI 860585 + paclitaxel

exemestane DRUG

exemestane once daily

BI 860585 + exemestane

paclitaxel DRUG

paclitaxel once weekly

BI 860585 + paclitaxel

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.
• 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;
• 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.

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (4)

Brussels - UNIV Saint-Luc

Brussels, 1200, Belgium

Location

UNIV UZ Gent

Ghent, 9000, Belgium

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Azienda Ospedaliera di Parma

Parma, 43126, Italy

Location

MeSH Terms

Conditions

Neoplasms

Interventions

exemestane; Paclitaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Limitations and Caveats

The trial was discontinued at the end of the dose-escalation phase for each treatment arm, before starting the expansion phase.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Centre
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2013
• First Posted: September 10, 2013
• Study Start: September 5, 2013
• Primary Completion: July 30, 2016
• Study Completion: June 22, 2017
• Last Updated: January 4, 2019
• Results First Posted: January 4, 2019

Record last verified: 2018-06

Locations

BE (2); IT (2)