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About
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).
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Inclusion criteria
Inclusion criteria only for patients entering phase Ib escalation and phase II:
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:
Inclusion criterion only for patients entering phase Ib expansion cohort:
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:
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:
Additional exclusion criterion for patients undergoing tumour biopsy:
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120 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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