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 Disease Progression on Docetaxel-Based Chemotherapy and Abiraterone
Overview
- Phase
- Phase 1
- Intervention
- BI 836845
- Conditions
- Prostatic Neoplasms, Castration-Resistant
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 120
- Locations
- 27
- Primary Endpoint
- Phase Ib Escalation Part: Number of Patients With Dose Limiting Toxicities (DLTs)
- Status
- Completed
- Last Updated
- 9 months ago
Overview
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
BI 836845 & Enzalutamide
Intervention: BI 836845
BI 836845 & Enzalutamide
Intervention: Enzalutamide
Enzalutamide
Intervention: Enzalutamide
Outcomes
Primary Outcomes
Phase Ib Escalation Part: Number of Patients With Dose Limiting Toxicities (DLTs)
Time Frame: From first administration of xentuzumab up to start of Cycle 2, up to 28 days.
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.
Phase Ib Escalation Part: Maximum Tolerated Dose (MTD) Based on the Occurrence of Dose Limiting Toxicity (DLT) During the First Treatment Course
Time Frame: From first administration of xentuzumab up to start of Cycle 2, up to 28 days.
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.
Phase Ib Expansion Part: Prostate Specific Antigen (PSA) Response
Time Frame: 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.
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.
Phase II Part: Progression Free Survival (PFS) Based on Investigator Assessment
Time Frame: From randomisation until radiological tumor progression or death from any cause, whichever occurred earlier, up to 1269 days.
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.
Secondary Outcomes
- 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.)
- Phase II Part: Maximum Decline in Prostate Specific Antigen (PSA)(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.)
- Phase II Part: Percentage Change in Prostate Specific Antigen (PSA) at Week 12(At baseline and at Week 12.)
- Phase II Part: Prostate Specific Antigen (PSA) Response(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.)
- Phase II Part: Circulating Tumour Cells (CTC) Reduction Defined as CTC Decline From ≥5 to <5 Cells Per 7.5 mL Blood for at Least One Post-baseline Time-point(Prior to study drug administration at Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 5 Day 1, Cycle 7 Day 1 and then every 12 weeks thereafter, until end of treatment. Up to 40.1 months.)
- Phase II Part: Maximum Decline (%) in Circulating Tumour Cells (CTC) Counts(Prior to study drug administration at Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 5 Day 1, Cycle 7 Day 1 and then every 12 weeks thereafter, until end of treatment. Up to 40.1 months.)
- Phase II Part: Circulating Tumour Cells (CTC) Status at Week 12(At Week 12.)