BI836845 Plus Enzalutamide in Castrate Resistant Prostate Cancer (CRPC)

NCT02204072 | Completed Phase 1 Results

• 2 other identifiers: 1280.82013-004011-41
• Study Type: interventional
• Target: 120
• Locations: 8 countries
• Sites: 27

Brief Summary

The overall aim of the trial is to investigate the safety and anti-tumour activity of an experimental drug BI 836845 taken together with the prostate cancer drug, enzalutamide, compared to enzalutamide given alone, in castrate resistant prostate cancer (CRPC) patients that have previously been treated and failed on docetaxel and abiraterone treatments. Initially, a tolerability and safety phase (phase Ib escalation) will be performed to confirm the maximum tolerated dose (MTD), or recommended doses of both BI 836845 and enzalutamide that can be taken together. Once the MTD, or recommended phase II dose, have been determined an expansion cohort will also be explored (phase Ib expansion) in CRPC patients already taking enzalutamide and have a rise in prostate serum antigen (PSA) levels. Patients may not have received prior docetaxel or abiraterone. Patients in this cohort will receive the MTD, or recommended phase II dose, of BI 836845 and enzalutamide determined in the phase Ib escalation phase. The randomised trial (phase II) will be an open label, parallel group study design in a 1:1 ratio to which patients will receive either BI 836845 plus enzalutamide (Arm A) at the MTD/recommended doses, or enzalutamide alone (Arm B). In all parts of the trial safety, anti-tumour activity will be assessed, in addition to circulating tumour cells (CTC), prostate serum antigen (PSA) response and progression, and determination of Overall Survival (OS).

Conditions

Prostatic Neoplasms, Castration-Resistant

Outcome Measures

Primary Outcomes (4)

• Phase Ib Escalation Part: Number of Patients With Dose Limiting Toxicities (DLTs)

  Number of patients with DLTs were used to determine the maximum tolerated dose (MTD) in the Phase Ib escalation part. The MTD in this study was defined as the highest protocol dose level of xentuzumab in combination with enzalutamide, at which no more than 1 out of 6 patients in a cohort experienced a DLT during the MTD evaluation period.

  From first administration of xentuzumab up to start of Cycle 2, up to 28 days.

• Phase Ib Escalation Part: Maximum Tolerated Dose (MTD) Based on the Occurrence of Dose Limiting Toxicity (DLT) During the First Treatment Course

  Maximum tolerated dose (MTD) based on the occurrence of dose limiting toxicity (DLT) during the first treatment course. The MTD in this study was defined as the highest protocol dose level of xentuzumab in combination with enzalutamide, at which no more than 1 out of 6 patients in a cohort experienced a DLT during the MTD evaluation period.

  From first administration of xentuzumab up to start of Cycle 2, up to 28 days.

• Phase Ib Expansion Part: Prostate Specific Antigen (PSA) Response

  The primary endpoint of the Phase Ib expansion part was PSA response. PSA response was defined as a decline in PSA value \>50% compared to baseline which was confirmed by the next available value occurring at least 3 weeks later. The confirmatory value had to be at least 50% lower than the baseline, but could be higher than the first PSA value taken into account for response. However the confirmatory value was not allowed to be 50% higher than this first PSA value. If it was ≥ 50% higher than the first PSA value, the next available sample was to be taken to determine if response had been achieved. The date of response was the date that the first 50% (or greater) decline was observed. Number of participants with response is reported.

  At Cycle 1 Day 1 before study treatment and from Cycle 3 Day 1 and Day 1 of every cycle thereafter until the end of treatment, up to 35 months.

• Phase II Part: Progression Free Survival (PFS) Based on Investigator Assessment

  PFS was defined as the time from randomisation until radiological tumour progression in bone (based on Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria) or soft tissue (based on modified RECIST 1.1) or death from any cause, whichever occurred earlier. Clinical disease progression was not considered for determination of a PFS event, unless the outcome of the progression was death. Median PFS time in months is reported. PFS was calculated as follows: For patients with 'event' as an outcome for PFS (according to modified RECIST version 1.1 or PCWG2): PFS \[days\] = date of outcome - date of randomisation + 1. For patients with 'censored' as an outcome for PFS (according to modified RECIST version 1.1 or PCWG2): PFS (censored) \[days\] = date of outcome - date of randomisation + 1.

  From randomisation until radiological tumor progression or death from any cause, whichever occurred earlier, up to 1269 days.

Secondary Outcomes (11)

• Phase Ib Expansion Part: Progression Free Survival (PFS) Based on Investigator Assessment

  From first treatment administration of any study medication until radiological tumor progression or death from any cause, whichever occurred earlier, up to 1114 days.

• Phase Ib Expansion Part: Changes in Circulating Tumour Cells (CTC) Response - CTC Reduction From >=5 to <5 Cells Per 7.5 mL Blood for at Least One Post-baseline Time Point

  Prior to study drug administration at Day 1 Cycle 1, Day 1 Cycle 2, Day 1 Cycle 3, Day 1 Cycle 5, Day 1 Cycle 7 and every 12 weeks thereafter, up to end of treatment. Up to 35 months.

• Phase II Part: Radiological Progression Free Survival (PFS), Based on Central Review

  From randomisation until radiological tumor progression or death from any cause, whichever occurred earlier, up to 1269 days.

• Phase II Part: Overall Survival (OS)

  From randomisation until radiological tumor progression or death from any cause (until cut-off date for final analysis), whichever occurred earlier, up to 1269 days.

• Phase II Part: Time to Prostate Specific Antigen (PSA) Progression

  At screening, at Cycle 1 Day 1 and from Cycle 3 Day 1 and at Day 1 of every cycle thereafter until end of treatment, up to 40.1 months.

Study Arms (2)

BI 836845 & Enzalutamide

EXPERIMENTAL

Drug: BI 836845; Drug: Enzalutamide

Enzalutamide

ACTIVE COMPARATOR

Drug: Enzalutamide

Interventions

BI 836845 DRUG

BI 836845 & Enzalutamide

Enzalutamide DRUG

Enzalutamide

Eligibility Criteria

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

You may qualify if:

• The patient has histologically, or cytologically, confirmed adenocarcinoma of the prostate.
• Male patient aged, equal to, or more than,18 years old.
• Patients with radiographic evidence of metastatic prostate cancer (stage M1 or D2). Distant metastases evaluable by radionuclide bone scan, CT scan, or MRI within 28 days before the start of study treatment.
• Patients with a prostate serum antigen (PSA), equal to, or more than, 5 nanograms per mililiter (ng/mL).
• Patients with prior surgical or chemical castration with a serum testosterone of \<50 ng/mL. If the method of castration is luteinizing hormone releasing level hormone (LHRH) agonists, the patient must be willing to continue the use of LHRH agonists during protocol treatment.
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.
• Cardiac left ventricular function with resting ejection fraction \>50% as determined by echocardiogram (ECHO) or multigated acquisition scan (MUGA).
• Absolute neutrophil count (ANC) \>=1500/microlitre (uL).
• Haemoglobin \>=9 gram per deciliter (g/dL).
• Platelets \>=100,000/uL.
• Bilirubin \<= 1.5 times the upper limit of normal (ULN).
• Aspartate transaminase (AST) and alanine transaminase (ALT) \<= 2.5 times the ULN(or \<= 5 times the ULN if liver metastases are present).
• Creatinine \<= 1.5 x ULN.
• International normalized ratio (INR) \</= 2 and a partial thromboplastin time (PTT) \</= 5 seconds above the ULN (unless on oral anticoagulant therapy). Patients receiving full dose anticoagulation therapy are eligible provided they meet all other criteria, are on a stable dose of oral anticoagulant or low molecular weight heparin (except warfarin or coumarin-like anticoagulants, which are not permitted).
• Fasting plasma glucose \< 8.9 millimols per liter (mmol/L) (\< 160 milligrams per deciliter (mg/dL) and glycated haemoglobin (hemoglobin A1c (HbA1c)) \< 8.0%.

You may not qualify if:

• Prior therapy with agents targeting Insulin Growth Factor (IGF) and/or Insulin Growth Factor Receptor (IGFR) pathway.
• Patients that have been treated with any of the following within 4 weeks of starting trial treatment: chemotherapy, immunotherapy, biological therapies, molecular targeted, hormone therapy (except LHRH agonists and LHRH antagonists), radiotherapy (except in case of localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture which can then be completed within 2 weeks prior to study treatment).
• Use of any investigational drug within 4 weeks before start of trial treatment or concomitantly with this trial.
• Patients that have been treated with strong cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) inhibitors, CYP2C8 inducers, within 2 weeks of starting the trial treatment.
• Fridericia´s Corrected QT interval (QTcF) prolongation \> 450 ms or QT prolongation deemed clinically relevant by the investigator (e.g., congenital long QT syndrome). The QTcF will be calculated as the mean of the 3 ECGs taken at screening.
• Patients with small cell or neuroendocrine tumours.
• Patients with known or suspected leptomeningeal metastases.
• Uncontrolled or poorly controlled hypertension.
• Known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness.
• Patients with epilepsy, seizures, or predisposing factors for seizure as judged by the investigator.
• Patients unable to comply with the protocol as judged by the investigator.
• Active alcohol or active drug abuse as judged by the investigator.
• A history of allergy to human monoclonal antibodies.
• Patients who are sexually active and unwilling to use a medically acceptable method of contraception, e.g. condom plus spermicide use for participating males, plus another form of birth control such as implants, injectables, combined oral contraceptives, intrauterine devices for female partners, during the trial and for at least three months after end of active therapy. Men unwilling to agree to not donate sperm while on trial drug and up to 6 months following the last dose of trial drug.
• Previous or concomitant malignancies at any other site with the exception of the following:

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (27)

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

NewYork-Presbyterian/Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Oregon Health and Sciences University

Portland, Oregon, 97239, United States

Location

Prince of Wales Hospital

Hong Kong, 999077, Hong Kong

Location

Queen Mary Hospital

Hong Kong, 999077, Hong Kong

Location

Erasmus MC - Daniel den Hoed

Rotterdam, 3075 EA, Netherlands

Location

Tweesteden Ziekenhuis, locatie Tilburg

Tilburg, 5042 AD, Netherlands

Location

National Cancer Centre Singapore

Singapore, 169610, Singapore

Location

OncoCare Cancer Centre

Singapore, 258499, Singapore

Location

Tan Tock Seng Hospital

Singapore, 308433, Singapore

Location

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Asan Medical Center

Seoul, 138-736, South Korea

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Duran i Reynals

L'Hospitalet de Llobregat, 08908, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

The Clatterbridge Cancer Centre

Bebington, Wirral, CH63 4JY, United Kingdom

Location

Velindre Cancer Centre

Cardiff, CF14 2TL, United Kingdom

Location

The Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

The Royal Marsden Hospital, Sutton

Sutton, SM2 5PT, United Kingdom

Location

Related Links

• Related Info

MeSH Terms

Conditions

Prostatic Neoplasms, Castration-Resistant

Interventions

xentuzumab; enzalutamide

Condition Hierarchy (Ancestors)

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

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

clintriage.rdg@boehringer-ingelheim.com

18002430127

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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2014
• First Posted: July 30, 2014
• Study Start: November 11, 2014
• Primary Completion: October 18, 2019
• Study Completion: June 1, 2023
• Last Updated: July 15, 2025
• Results First Posted: July 15, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.

Locations

NL (2); ES (7); US (3); HK (2); KR (2); GB (5); SG (3); TW (3)