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

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ClinicalTrials.gov Identifier: NCT01938846
Recruitment Status : Completed
First Posted : September 10, 2013
Results First Posted : January 4, 2019
Last Update Posted : January 4, 2019
Sponsor:
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Neoplasms Drug: BI 860585 Drug: exemestane Drug: paclitaxel Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 5, 2013
Actual Primary Completion Date : July 30, 2016
Actual Study Completion Date : June 22, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: BI 860585
Multiple ascending doses of BI 860585 administered continuously in a 28-day cycle, including food interaction cohorts
Drug: BI 860585
BI 860585 multiple dose escalation, once daily

Experimental: BI 860585 + paclitaxel
Multiple ascending doses of BI 860585 in combination with fixed dose paclitaxel
Drug: BI 860585
BI 860585 multiple dose escalation, once daily

Drug: paclitaxel
paclitaxel once weekly

Experimental: BI 860585 + exemestane
Multiple ascending doses of BI 860585 in combination with fixed dose exemestane
Drug: exemestane
exemestane once daily

Drug: BI 860585
BI 860585 multiple dose escalation, once daily




Primary Outcome Measures :
  1. The Number of Patients With Dose-Limiting Toxicities (DLTs) in the First Course of Each Treatment Arm [ Time Frame: 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.

  2. The Maximum Tolerated Dose (MTD) for Each Treatment Arm [ Time Frame: 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 Outcome Measures :
  1. Objective Response Rate (Complete Response or Partial Response as Per the Response Evaluation Criteria In Solid Tumors Criteria [RECIST], Version 1.1) [ 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 ]
    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)

  2. 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) [ 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. ]
    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)

  3. Duration of Clinical Benefit [ 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 ]
    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.

  4. Duration of 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 ]
    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.

  5. Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to Infinity (AUC0-∞) [ 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. ]
    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

  6. Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to 24 Hours (AUC0-24) [ 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. ]
    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

  7. Half Life of BI 860585 (t1/2) [ 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. ]
    t ½, half-life of BI 860585 in plasma over a dosing interval after single administration of BI 860585

  8. Maximum Measured Concentration of BI 860585 (Cmax) [ 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. ]
    Cmax, maximum measured concentration of BI 860585 in plasma over a dosing interval after single administration of BI 860585

  9. Time to Maximum Concentration of BI 860585 (Tmax) [ 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. ]
    Tmax, Time to maximum concentration of BI 860585 in plasma over a dosing interval after single administration of BI 860585

  10. Area Under the Concentration-time Curve of BI 860585 in Plasma Over a Dosing Interval at Steady State (AUCτ,ss) [ 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. ]
    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.

  11. Half Life of BI 860585 at Steady State (t1/2,ss) [ 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. ]
    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.

  12. Time to Maximum Concentration of BI 860585 at Steady State (Tmax,ss) [ 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. ]
    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.

  13. Maximum Measured Concentration of BI 860585 in Plasma at Steady State (Cmax,ss) [ 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. ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01938846


Locations
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Belgium
Brussels - UNIV Saint-Luc
Bruxelles, Belgium, 1200
UNIV UZ Gent
Gent, Belgium, 9000
Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milano, Italy, 20133
Azienda Ospedaliera di Parma
Parma, Italy, 43126
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
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Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  Study Documents (Full-Text)

Documents provided by Boehringer Ingelheim:
Statistical Analysis Plan  [PDF] August 17, 2016
Study Protocol  [PDF] February 13, 2015


Additional Information:
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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01938846     History of Changes
Other Study ID Numbers: 1325.1
2013-000765-36 ( EudraCT Number )
First Posted: September 10, 2013    Key Record Dates
Results First Posted: January 4, 2019
Last Update Posted: January 4, 2019
Last Verified: June 2018

Additional relevant MeSH terms:
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Paclitaxel
Albumin-Bound Paclitaxel
Exemestane
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs