BI836845 Plus Enzalutamide in Castrate Resistant Prostate Cancer (CRPC)

NCT ID: NCT02204072

Last Updated: 2025-07-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-11
• Study Completion Date: 2023-06-01

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BI 836845 & Enzalutamide

Group Type: EXPERIMENTAL

BI 836845

Intervention Type: DRUG

Enzalutamide

Intervention Type: DRUG

Enzalutamide

Group Type: ACTIVE_COMPARATOR

Enzalutamide

Intervention Type: DRUG

Interventions

BI 836845

Intervention Type: DRUG

Enzalutamide

Intervention Type: DRUG

Enzalutamide

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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%.

• Patients who have disease progression during, or after, receiving docetaxel and have had at least 12 weeks of treatment and in the opinion of the investigator are unlikely to derive significant benefit from additional docetaxel-based therapy, or were intolerant to therapy with this agent.
• Patients who have disease progression during, or after, receiving abiraterone treatment in any setting.
• Patients must have progressive disease defined as at least one of the following:

1. Progressive measurable disease: using conventional solid tumour criteria RECIST 1.1.

2. Bone scan progression: at least two new lesions on bone scan, plus a rising PSA as described in (c) below.

3. Increasing PSA level: at least two consecutive rising PSA values over a reference value (PSA #1) taken at least 1 week apart. A third PSA (PSA #3) is required to be greater than PSA #2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2.

Inclusion criterion only for patients entering phase Ib expansion cohort:

• Patients must be receiving continuous enzalutamide treatment and show a rise in PSA level: at least two consecutive rising PSA values over a reference value (PSA #1) taken at least 1 week apart. A third PSA (PSA #3) is required to be greater than PSA #2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2.
• Archive tumour tissue is available prior to recruitment for pharmacogenomic tests

Exclusion Criteria

• 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:

• benign basal cell carcinoma
• benign low grade transitional cell carcinoma of the bladder
• other effectively treated malignancy that has been in remission for more than 5 years and is considered to be cured
• Only for patients entering phase Ib dose escalation and phase II cohorts:
• Patients who have received more than 2 prior non-docetaxel containing cytotoxic chemotherapy regimens for Metastatic Castration-Resistant Prostate Cancer (mCRPC).
• Patients who have received a taxane based treatment or abiraterone, within 4 weeks before start of study treatment.
• Patients that have received prior enzalutamide in any setting will not be eligible.

Exclusion criterion only for patients entering phase Ib expansion cohort:

• Patients that have received prior taxane-based chemotherapy or abiraterone in any setting will not be eligible for the expansion cohort.

Additional exclusion criterion for patients undergoing tumour biopsy:

• For patients that are to undergo the tumour biopsy, a history of a hereditary bleeding disorder, or clinically relevant major bleeding event in the past 6 months, as judged by the investigator.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

Karmanos Cancer Institute

Detroit, Michigan, United States

NewYork-Presbyterian/Weill Cornell Medical Center

New York, New York, United States

Oregon Health and Sciences University

Portland, Oregon, United States

Prince of Wales Hospital

Hong Kong, , Hong Kong

Queen Mary Hospital

Hong Kong, , Hong Kong

Erasmus MC - Daniel den Hoed

Rotterdam, , Netherlands

Tweesteden Ziekenhuis, locatie Tilburg

Tilburg, , Netherlands

National Cancer Centre Singapore

Singapore, , Singapore

OncoCare Cancer Centre

Singapore, , Singapore

Tan Tock Seng Hospital

Singapore, , Singapore

Samsung Medical Center

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Hospital Vall d'Hebron

Barcelona, , Spain

Hospital Clínic de Barcelona

Barcelona, , Spain

Hospital Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Duran i Reynals

L'Hospitalet de Llobregat, , Spain

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Hospital Ramón y Cajal

Madrid, , Spain

Instituto Valenciano de Oncología

Valencia, , Spain

Taichung Veterans General Hospital

Taichung, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

The Clatterbridge Cancer Centre

Bebington, Wirral, , United Kingdom

Velindre Cancer Centre

Cardiff, , United Kingdom

The Christie Hospital

Manchester, , United Kingdom

Churchill Hospital

Oxford, , United Kingdom

The Royal Marsden Hospital, Sutton

Sutton, , United Kingdom

Countries

United States; Hong Kong; Netherlands; Singapore; South Korea; Spain; Taiwan; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.mystudywindow.com

Related Info

Other Identifiers

2013-004011-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1280.8

Identifier Type: -

Identifier Source: org_study_id