Clinical Trial: BI836845 Plus Enzalutamide in Castrate Resistant Prostate Cancer (CRPC)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase Ib/II, Multicentre, Open Label, Randomized Study of BI 836845 in Combination With Enzalutamide, Versus Enzalutamide Alone, in Metastatic Castration-Resistant Prostate Cancer (CRPC) Following D

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).


Detailed Summary:
Sponsor: Boehringer Ingelheim

Current Primary Outcome:

  • Number of patients with dose limiting toxicities (phase Ib escalation) [ Time Frame: 6 months ]
  • Maximum tolerated dose (phase Ib escalation) [ Time Frame: 6 months ]
  • Prostate Surface Antigen (PSA) response - defined as a decline in PSA value >50%, which is confirmed by a second value 3 to 4 weeks apart (phase Ib expansion) [ Time Frame: Up to 3 years ]
  • Radiological Progression free survival - time from randomisation to disease progression based on investigator assessment in bone, or soft tissue, or death (phase II) [ Time Frame: Up to 3 years ]


Original Primary Outcome:

  • Number of patients with dose limiting toxicities (phase Ib escalation) [ Time Frame: 6 months ]
  • Maximum tolerated dose (phase Ib escalation) [ Time Frame: 6 months ]
  • PSA response - defined as a decline in PSA value >50%, which is confirmed by a second value 3 or more weeks later (phase Ib expansion) [ Time Frame: Up to 3 years ]
  • Radiological progression free survival - defined as time from randomisation to disease progression based on central review in bone or soft tissue based on modified RECIST 1.1 where applicable, or death (phase II) [ Time Frame: Up to 3 years ]


Current Secondary Outcome:

  • Overall survival - defined as the time from randomisation to death from any cause (phase II) [ Time Frame: Up to 3 years ]
  • Time to prostate serum antigen (PSA) progression - defined as the date that a 25% or greater increase in PSA, and an absolute increase of 2 ng/mL or more from the nadir, is documented, which is confirmed by a second value 3 or more weeks later (phase II) [ Time Frame: Up to 3 years ]
  • Maximum decline in PSA - compared to baseline that occurs at any point after treatment start (phase II) [ Time Frame: Up to 3 years ]
  • Percentage change in PSA - from baseline to week 12 of treatment (phase II) [ Time Frame: Up to 3 years ]
  • CTC response-CTC reduction compared to baseline for at least one time point after treatment start assessed by maximum change in CTC counts compared to baseline that occurs at any point after treatment start (phase II) [ Time Frame: Up to 3 years ]
  • Radiological progression free survival - defined as time from randomisation to disease progression based on investigator assessment in bone based on PCWG2 or soft tissue based on modified RECIST 1.1 where applicable, or death (phase Ib expansion) [ Time Frame: Up to 3 years ]
  • Changes in CTC response - CTC reduction compared to baseline for at least one time point after treatment start assessed by CTC decline from, equal to, or more than, 5 to <5 cells per 7.5ml blood (phase II) [ Time Frame: Up to 3 years ]
  • Changes in circulating tumour cells (CTC) response - CTC reduction compared to baseline for at least one time point after treatment defined as CTC decline from, equal to, or more than, 5 to <5 cells per 7.5ml blood (phase Ib expansion) [ Time Frame: Up to 3 years ]
  • PSA response - defined as a decline in PSA value >50%, which is confirmed by a second value 3 to 4 weeks apart (phase II) [ Time Frame: Up to 3 years ]


Original Secondary Outcome:

  • Changes in circulating tumour cells (CTC) response - CTC reduction compared to baseline for at least one time point after treatment start assessed by CTC fall from, equal to, or more than, 5 to <5 cells per 7.5ml blood (phase Ib expansion) [ Time Frame: Up to 3 years ]
  • CTC response - CTC reduction compared to baseline for at least one time point after treatment start assessed by a decline of at least 30% in CTC counts (phase Ib expansion) [ Time Frame: Up to 3 years ]
  • Radiological progression free survival - defined as time from randomisation to disease progression based on central review in bone or soft tissue based on modified RECIST 1.1 where applicable, or death (phase Ib expansion) [ Time Frame: Up to 3 years ]
  • Overall survival - defined as the time from randomisation to death from any cause (phase II) [ Time Frame: Up to 3 years ]
  • Time to prostate serum antigen (PSA) progression - defined as the date that a 25% or greater increase in PSA, and an absolute increase of 2 ng/mL or more from the nadir, is documented, which is confirmed by a second value 3 or more weeks later (phase II) [ Time Frame: Up to 3 years ]
  • Maximum decline in PSA - compared to baseline that occurs at any point after treatment start (phase II) [ Time Frame: Up to 3 years ]
  • Percentage change in PSA - from baseline to week 12 of treatment (phase II) [ Time Frame: Up to 3 years ]
  • PSA response - defined as a decline in PSA value >50%, which is confirmed by a second value 3 or more weeks later (phase II) [ Time Frame: Up to 3 years ]
  • CTC response - CTC reduction compared to baseline for at least one time point after treatment start assessed by CTC fall from, equal to, or more than, 5 to <5 cells per 7.5ml blood (phase II) [ Time Frame: Up to 3 years ]
  • CTC response-CTC reduction compared to baseline for at least one time point after treatment start assessed by maximum change in CTC counts compared to baseline that occurs at any point after treatment start (phase II) [ Time Frame: Up to 3 years ]


Information By: Boehringer Ingelheim

Dates:
Date Received: July 29, 2014
Date Started: November 11, 2014
Date Completion: January 30, 2018
Last Updated: May 17, 2017
Last Verified: May 2017