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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-004011-41 | EudraCT Number |
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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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BI 836845 & Enzalutamide | Experimental |
| |
| Enzalutamide | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BI 836845 | Drug |
| ||
| Enzalutamide |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Phase Ib Expansion 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 first treatment administration + 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 first treatment administration + 1. |
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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:
- 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:
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States | ||
| NewYork-Presbyterian/Weill Cornell Medical Center |
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| Label | URL |
|---|---|
| Related Info | View source |
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After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website. The data shared are the raw clinical study data sets.
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.
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'.
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated
A multicentre, open-label, randomised study to determine the safety, tolerability and anti-tumour activity of xentuzumab (BI 836845) in combination with enzalutamide in patients with advanced prostate cancer that has spread. The trial consists of 3 parts: Phase 1b dose escalation part, Phase 1b expansion part, Phase 2 two arm, parallel design.
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase Ib Escalation: 750 mg Xentuzumab + 160 mg Enzalutamide | 750 milligram (mg) xentuzumab (10mg/milliliter (mL)) was supplied in 20mL vials and diluted in physiological sodium chloride solution (0.9%)) as liquid formulation was administered as weekly 1-hour intravenous (i.v.) infusion on Days 1, 8, 15 and 22 together with four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Infusion duration of xentuzumab could be extended to more than 1 hour in case of infusion reaction or adverse events. Phase Ib escalation part. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 6, 2022 | May 29, 2024 |
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| Enzalutamide | Drug |
|
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. |
| 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 | 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. Number of participants with CTC Response (yes/no) is reported. | 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 | 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 first treatment administration + 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 first treatment administration + 1. | From randomisation until radiological tumor progression or death from any cause, whichever occurred earlier, up to 1269 days. |
| Phase II Part: Overall Survival (OS) | Overall survival (OS) defined as the time from randomisation to death from any cause. Median survival time in months is reported. Overall survival at cut-off date for final analysis (24-Oct-2019) is reported. | 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 | For the definition of time to PSA progression, the following rules are used:
Time to PSA progression [days] = date of PSA progression - date of randomisation + 1. For patients not presenting with PSA progression or being lost to follow-up: Time to PSA progression (censored) [days] = date of censoring - date of randomisation + 1. | 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) | Maximum decline in (PSA) compared to baseline. The maximum decline in PSA is defined as the change in PSA between the baseline PSA value and the minimum post-baseline PSA value. The change from baseline is defined as: Change from baseline in PSA (ng/mL) = PSA value post-baseline - PSA value at baseline. Maximum decline in PSA is defined as: Maximum decline in PSA (ng/mL) = min(PSA value post-baseline) - PSA value at baseline. | 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 | Percentage change in PSA from baseline to Week 12. Percentage change in PSA from baseline to week 12 of treatment is defined as: Percentage change in PSA (%) = 100*(PSA value at week 12 - PSA value at baseline)/PSA value at baseline For this assessment, it is allowed to take a value:
| At baseline and at Week 12. |
| Phase II Part: Prostate Specific Antigen (PSA) Response | PSA response - defined as a decline in PSA value >50% (which is confirmed by a second value 3 to 4 weeks apart). 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. Number of participants with response is reported. | 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 | CTC reduction is defined as CTC decline from ≥5 to <5 cells per 7.5 mL blood for at least one post-baseline time-point. Patients with a CTC value < 5 cells per 7.5mL blood at baseline, or with missing baseline values were not taken into consideration for this endpoint. Baseline value is the value collected before a patient starts treatment with trial medication. Number of participants per category is reported. | 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 | Maximum decline in CTC counts (in number of cells) compared with baseline that occurred at any point after treatment start , defined as the difference between the minimum post-baseline CTC value and the baseline CTC value. Patients with missing baseline value are considered missing for this criterion. Baseline value is the value collected before a patient starts treatment with trial medication. Positive values for maximum decline in CTC are possible in case no decline in CTC occurred. This indicates an increase in CTC. | 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 | CTC status (≥5 or <5 cells per 7.5mL blood) at Week 12. Number of participants per category is reported. | At Week 12. |
| New York |
| New York |
| 10065 |
| United States |
| Oregon Health and Sciences University | Portland | Oregon | 97239 | United States |
| Prince of Wales Hospital | Hong Kong | 999077 | Hong Kong |
| Queen Mary Hospital | Hong Kong | 999077 | Hong Kong |
| Erasmus MC - Daniel den Hoed | Rotterdam | 3075 EA | Netherlands |
| Tweesteden Ziekenhuis, locatie Tilburg | Tilburg | 5042 AD | Netherlands |
| National Cancer Centre Singapore | Singapore | 169610 | Singapore |
| OncoCare Cancer Centre | Singapore | 258499 | Singapore |
| Tan Tock Seng Hospital | Singapore | 308433 | Singapore |
| Samsung Medical Center | Seoul | 135-710 | South Korea |
| Asan Medical Center | Seoul | 138-736 | South Korea |
| Hospital Vall d'Hebron | Barcelona | 08035 | Spain |
| Hospital ClÃnic de Barcelona | Barcelona | 08036 | Spain |
| Hospital Santa Creu i Sant Pau | Barcelona | 08041 | Spain |
| Hospital Duran i Reynals | L'Hospitalet de Llobregat | 08908 | Spain |
| Hospital General Universitario Gregorio Marañón | Madrid | 28007 | Spain |
| Hospital Ramón y Cajal | Madrid | 28034 | Spain |
| Instituto Valenciano de OncologÃa | Valencia | 46009 | Spain |
| Taichung Veterans General Hospital | Taichung | 40705 | Taiwan |
| National Taiwan University Hospital | Taipei | 100 | Taiwan |
| Taipei Veterans General Hospital | Taipei | 11217 | Taiwan |
| The Clatterbridge Cancer Centre | Bebington, Wirral | CH63 4JY | United Kingdom |
| Velindre Cancer Centre | Cardiff | CF14 2TL | United Kingdom |
| The Christie Hospital | Manchester | M20 4BX | United Kingdom |
| Churchill Hospital | Oxford | OX3 7LE | United Kingdom |
| The Royal Marsden Hospital, Sutton | Sutton | SM2 5PT | United Kingdom |
| FG001 | Phase Ib Escalation: 1000 mg Xentuzumab + 160 mg Enzalutamide | 1000 milligram (mg) xentuzumab (10mg/mL was supplied in 20mL vials and diluted in physiological sodium chloride solution (0.9%)) as liquid formulation was administered as weekly 1-hour intravenous (i.v.) infusion on Days 1, 8, 15 and 22 together with four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Infusion duration of xentuzumab could be extended to more than 1 hour in case of infusion reaction or adverse events. Phase Ib escalation part. |
| FG002 | Phase Ib Expansion: 1000 mg Xentuzumab + 160 mg Enzalutamide | 1000 milligram (mg) xentuzumab (10mg/mL was supplied in 20mL vials and diluted in physiological sodium chloride solution (0.9%)) as liquid formulation was administered as weekly 1-hour intravenous (i.v.) infusion on Days 1, 8, 15 and 22 together with four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Infusion duration of xentuzumab could be extended to more than 1 hour in case of infusion reaction or adverse events. Phase Ib expansion part. |
| FG003 | Phase II: 1000 mg Xentuzumab + 160 mg Enzalutamide | 1000 milligram (mg) xentuzumab (10mg/mL was supplied in 20mL vials and diluted in physiological sodium chloride solution (0.9%)) as liquid formulation was administered as weekly 1-hour intravenous (i.v.) infusion on Days 1, 8, 15 and 22 together with four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Infusion duration of xentuzumab could be extended to more than 1 hour in case of infusion reaction or adverse events. Phase II part. |
| FG004 | Phase II: 160 mg Enzalutamide | Four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Phase II part. |
| Treated |
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| Discontinued Xentuzumab Due to Progressive Disease |
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| Discontinued Xentuzumab Due to Adverse Event |
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| Discontinued Xentuzumab Due to Withdrawal by Subject |
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| Discontinued Xentuzumab Due to Other Reason |
|
| COMPLETED | Completed=Number of patients on treatment |
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| NOT COMPLETED |
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|
Treated Set (TS): All patients who were documented to have received and taken at least one dose of any study medication during the treatment cycles (from Day 1).
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| ID | Title | Description |
|---|---|---|
| BG000 | Phase Ib Escalation: 750 mg Xentuzumab + 160 mg Enzalutamide | 750 milligram (mg) xentuzumab (10mg/milliliter (mL)) was supplied in 20mL vials and diluted in physiological sodium chloride solution (0.9%)) as liquid formulation was administered as weekly 1-hour intravenous (i.v.) infusion on Days 1, 8, 15 and 22 together with four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Infusion duration of xentuzumab could be extended to more than 1 hour in case of infusion reaction or adverse events. Phase Ib escalation part. |
| BG001 | Phase Ib Escalation: 1000 mg Xentuzumab + 160 mg Enzalutamide | 1000 milligram (mg) xentuzumab (10mg/mL was supplied in 20mL vials and diluted in physiological sodium chloride solution (0.9%)) as liquid formulation was administered as weekly 1-hour intravenous (i.v.) infusion on Days 1, 8, 15 and 22 together with four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Infusion duration of xentuzumab could be extended to more than 1 hour in case of infusion reaction or adverse events. Phase Ib escalation part. |
| BG002 | Phase Ib Expansion: 1000 mg Xentuzumab + 160 mg Enzalutamide | 1000 milligram (mg) xentuzumab (10mg/mL was supplied in 20mL vials and diluted in physiological sodium chloride solution (0.9%)) as liquid formulation was administered as weekly 1-hour intravenous (i.v.) infusion on Days 1, 8, 15 and 22 together with four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Infusion duration of xentuzumab could be extended to more than 1 hour in case of infusion reaction or adverse events. Phase Ib expansion part. |
| BG003 | Phase II: 1000 mg Xentuzumab + 160 mg Enzalutamide | 1000 milligram (mg) xentuzumab (10mg/mL was supplied in 20mL vials and diluted in physiological sodium chloride solution (0.9%)) as liquid formulation was administered as weekly 1-hour intravenous (i.v.) infusion on Days 1, 8, 15 and 22 together with four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Infusion duration of xentuzumab could be extended to more than 1 hour in case of infusion reaction or adverse events. Phase II part. |
| BG004 | Phase II: 160 mg Enzalutamide | Four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Phase II part. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Prostate Surface Antigen (PSA) at baseline | Phase 1b escalation part and Phase 1b expansion part: Treated Set. Phase II: Randomised Set. | Mean | Standard Deviation | Micorgram / Liter |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
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| Primary | 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. | MTD-set: The MTD set defined the set of patients in the Phase Ib escalation part who were fully evaluable for determination of the MTD in the first treatment course. 1 patient in the 1000 mg Xentuzumab + 160 mg Enzalutamide arm was not evaluable for the MTD determination due to missed doses. Phase Ib escalation part. | Posted | Count of Participants | Participants | From first administration of xentuzumab up to start of Cycle 2, up to 28 days. |
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| Primary | 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. | MTD-set: The MTD set defined the set of patients in the Phase Ib escalation part who were fully evaluable for determination of the MTD in the first treatment course. 1 patient in the 1000 mg Xentuzumab + 160 mg Enzalutamide arm was not evaluable for the MTD determination due to missed doses. Phase Ib escalation part. | Posted | Number | Milligram | From first administration of xentuzumab up to start of Cycle 2, up to 28 days. |
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| Primary | 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. | Treated Set (TS): All patients who were documented to have received and taken at least one dose of any study medication during the treatment cycles (from Day 1). Phase Ib expansion part. | Posted | Count of Participants | Participants | 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. |
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| Primary | 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. | Randomised Set (RS): All randomised patients in the Phase II part, regardless of whether or not they received treatment. Patients were assigned to xentuzumab in combination with enzalutamide or enzalutamide alone. Phase II part. | Posted | Median | 95% Confidence Interval | Months | From randomisation until radiological tumor progression or death from any cause, whichever occurred earlier, up to 1269 days. |
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| Secondary | Phase Ib Expansion 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 first treatment administration + 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 first treatment administration + 1. | Treated Set (TS): All patients who were documented to have received and taken at least one dose of any study medication during the treatment cycles (from Day 1). Phase Ib expansion part. | Posted | Median | 95% Confidence Interval | Months | From first treatment administration of any study medication until radiological tumor progression or death from any cause, whichever occurred earlier, up to 1114 days. |
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| Secondary | 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 | 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. Number of participants with CTC Response (yes/no) is reported. | Treated Set (TS): All patients who were documented to have received and taken at least one dose of any study medication during the treatment cycles (from Day 1). Only participants with baseline CTC value >= 5 cells per 7.5mL were included in the analysis. Phase Ib expansion part. | Posted | Count of Participants | Participants | 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. |
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| Secondary | Phase II Part: Radiological Progression Free Survival (PFS), Based on Central Review | 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 first treatment administration + 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 first treatment administration + 1. | Randomised Set: All randomised patients in the Phase II part, regardless of whether or not they received treatment. Patients were assigned to xentuzumab in combination with enzalutamide or enzalutamide alone. Phase II part. | Posted | Median | 95% Confidence Interval | Months | From randomisation until radiological tumor progression or death from any cause, whichever occurred earlier, up to 1269 days. |
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| Secondary | Phase II Part: Overall Survival (OS) | Overall survival (OS) defined as the time from randomisation to death from any cause. Median survival time in months is reported. Overall survival at cut-off date for final analysis (24-Oct-2019) is reported. | Randomised Set: All randomised patients in the Phase II part, regardless of whether or not they received treatment. Patients were assigned to xentuzumab in combination with enzalutamide or enzalutamide alone. Phase II part. | Posted | Median | 95% Confidence Interval | Months | 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. |
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| Secondary | Phase II Part: Time to Prostate Specific Antigen (PSA) Progression | For the definition of time to PSA progression, the following rules are used:
Time to PSA progression [days] = date of PSA progression - date of randomisation + 1. For patients not presenting with PSA progression or being lost to follow-up: Time to PSA progression (censored) [days] = date of censoring - date of randomisation + 1. | Randomised Set: All randomised patients in the Phase II part, regardless of whether or not they received treatment. Patients were assigned to xentuzumab in combination with enzalutamide or enzalutamide alone. Phase II part. | Posted | Median | 95% Confidence Interval | Months | 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. |
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| Secondary | Phase II Part: Maximum Decline in Prostate Specific Antigen (PSA) | Maximum decline in (PSA) compared to baseline. The maximum decline in PSA is defined as the change in PSA between the baseline PSA value and the minimum post-baseline PSA value. The change from baseline is defined as: Change from baseline in PSA (ng/mL) = PSA value post-baseline - PSA value at baseline. Maximum decline in PSA is defined as: Maximum decline in PSA (ng/mL) = min(PSA value post-baseline) - PSA value at baseline. | Randomised Set (RS): This patient set included all randomised patients in the Phase II part, regardless of whether or not they received treatment. Patients were assigned to xentuzumab in combination with enzalutamide or enzalutamide alone. Only participants with non-missing values were included in the analysis. Phase II part. | Posted | Mean | Standard Deviation | Microgram / Liter | 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. |
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| Secondary | Phase II Part: Percentage Change in Prostate Specific Antigen (PSA) at Week 12 | Percentage change in PSA from baseline to Week 12. Percentage change in PSA from baseline to week 12 of treatment is defined as: Percentage change in PSA (%) = 100*(PSA value at week 12 - PSA value at baseline)/PSA value at baseline For this assessment, it is allowed to take a value:
| Randomised Set: All randomised patients in the Phase II part, regardless of whether or not they received treatment. Patients were assigned to xentuzumab in combination with enzalutamide or enzalutamide alone. Only participants with non-missing values were included in the analysis. Phase II part. | Posted | Mean | Standard Deviation | Percentage change | At baseline and at Week 12. |
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| Secondary | Phase II Part: Prostate Specific Antigen (PSA) Response | PSA response - defined as a decline in PSA value >50% (which is confirmed by a second value 3 to 4 weeks apart). 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. Number of participants with response is reported. | Randomised Set (RS): This patient set included all randomised patients in the Phase II part, regardless of whether or not they received treatment. Patients were assigned to xentuzumab in combination with enzalutamide or enzalutamide alone. Phase II part. | Posted | Count of Participants | Participants | 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. |
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| Secondary | 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 | CTC reduction is defined as CTC decline from ≥5 to <5 cells per 7.5 mL blood for at least one post-baseline time-point. Patients with a CTC value < 5 cells per 7.5mL blood at baseline, or with missing baseline values were not taken into consideration for this endpoint. Baseline value is the value collected before a patient starts treatment with trial medication. Number of participants per category is reported. | Randomised Set (RS): This patient set included all randomised patients in the Phase II part, regardless of whether or not they received treatment. Patients were assigned to xentuzumab in combination with enzalutamide or enzalutamide alone. Only patients with baseline CTC value >=5 cells per 7.5mL were included in the analysis. Phase II part. | Posted | Count of Participants | Participants | 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. |
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| Secondary | Phase II Part: Maximum Decline (%) in Circulating Tumour Cells (CTC) Counts | Maximum decline in CTC counts (in number of cells) compared with baseline that occurred at any point after treatment start , defined as the difference between the minimum post-baseline CTC value and the baseline CTC value. Patients with missing baseline value are considered missing for this criterion. Baseline value is the value collected before a patient starts treatment with trial medication. Positive values for maximum decline in CTC are possible in case no decline in CTC occurred. This indicates an increase in CTC. | Randomised Set: All randomised patients in the Phase II part, regardless of whether or not they received treatment. Patients were assigned to xentuzumab in combination with enzalutamide or enzalutamide alone. Only participants with baseline CTC value were included in the analysis. Phase II part. | Posted | Mean | Standard Deviation | Percentage (%) | 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. |
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| Secondary | Phase II Part: Circulating Tumour Cells (CTC) Status at Week 12 | CTC status (≥5 or <5 cells per 7.5mL blood) at Week 12. Number of participants per category is reported. | Randomised Set: All randomised patients in the Phase II part, regardless of whether or not they received treatment. Patients were assigned to xentuzumab in combination with enzalutamide or enzalutamide alone. Phase II part. | Posted | Count of Participants | Participants | At Week 12. |
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[All cause mortality]: Up to 430 days for Phase 1b escalation, up to 1107 days Phase 1b expansion and up to 1322 days for Phase II part. [Serious and other Adverse events]. From first drug administration until last drug administration + residual effect period of 42 days, up to 370 days for Phase 1b escalation, up to 1107 days for Phase 1b expansion, up to 1262 days for Phase II.
Treated Set (TS): This patient set included all patients who were documented to have received and taken at least one dose of any study medication during the treatment cycles (from Day 1).
All-cause mortality includes all death throughout the whole study period, also including death reports after the cut-off date of the final analysis.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Phase Ib Escalation: 750 mg Xentuzumab + 160 mg Enzalutamide | 750 milligram (mg) xentuzumab (10mg/milliliter (mL)) was supplied in 20mL vials and diluted in physiological sodium chloride solution (0.9%)) as liquid formulation was administered as weekly 1-hour intravenous (i.v.) infusion on Days 1, 8, 15 and 22 together with four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Infusion duration of xentuzumab could be extended to more than 1 hour in case of infusion reaction or adverse events. Phase Ib escalation part. | 1 | 3 | 2 | 3 | 3 | 3 |
| EG001 | Phase Ib Escalation: 1000 mg Xentuzumab + 160 mg Enzalutamide | 1000 milligram (mg) xentuzumab (10mg/mL was supplied in 20mL vials and diluted in physiological sodium chloride solution (0.9%)) as liquid formulation was administered as weekly 1-hour intravenous (i.v.) infusion on Days 1, 8, 15 and 22 together with four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Infusion duration of xentuzumab could be extended to more than 1 hour in case of infusion reaction or adverse events. Phase Ib escalation part. | 2 | 7 | 5 | 7 | 7 | 7 |
| EG002 | Phase Ib Expansion: 1000 mg Xentuzumab + 160 mg Enzalutamide | 1000 milligram (mg) xentuzumab (10mg/mL was supplied in 20mL vials and diluted in physiological sodium chloride solution (0.9%)) as liquid formulation was administered as weekly 1-hour intravenous (i.v.) infusion on Days 1, 8, 15 and 22 together with four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Infusion duration of xentuzumab could be extended to more than 1 hour in case of infusion reaction or adverse events. Phase Ib expansion part. | 0 | 24 | 8 | 24 | 24 | 24 |
| EG003 | Phase II: 1000 mg Xentuzumab + 160 mg Enzalutamide | 1000 milligram (mg) xentuzumab (10mg/mL was supplied in 20mL vials and diluted in physiological sodium chloride solution (0.9%)) as liquid formulation was administered as weekly 1-hour intravenous (i.v.) infusion on Days 1, 8, 15 and 22 together with four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Infusion duration of xentuzumab could be extended to more than 1 hour in case of infusion reaction or adverse events. Phase II part. | 34 | 43 | 19 | 43 | 43 | 43 |
| EG004 | Phase II: 160 mg Enzalutamide | Four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Phase II part. | 31 | 43 | 17 | 43 | 43 | 43 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Cataract | Eye disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Retinal detachment | Eye disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Inguinal hernia | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Condition aggravated | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Osteomyelitis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Pulmonary sepsis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Acetabulum fracture | Injury, poisoning and procedural complications | MedDRA 26.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 26.1 | Systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA 26.1 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 26.1 | Systematic Assessment |
| |
| Patella fracture | Injury, poisoning and procedural complications | MedDRA 26.1 | Systematic Assessment |
| |
| Electrocardiogram T wave inversion | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.1 | Systematic Assessment |
| |
| Colon cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.1 | Systematic Assessment |
| |
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.1 | Systematic Assessment |
| |
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.1 | Systematic Assessment |
| |
| Meningioma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.1 | Systematic Assessment |
| |
| Metastases to bone | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.1 | Systematic Assessment |
| |
| Cauda equina syndrome | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hypersomnia | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Peripheral motor neuropathy | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Spinal cord compression | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Urinary tract obstruction | Renal and urinary disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pelvic pain | Reproductive system and breast disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Circulatory collapse | Vascular disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Orthostatic hypotension | Vascular disorders | MedDRA 26.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 26.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 26.1 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 26.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Electrocardiogram T wave inversion | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Amnesia | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Taste disorder | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Depressed mood | Psychiatric disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Nightmare | Psychiatric disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pelvic pain | Reproductive system and breast disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Abdominal pain lower | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Anal incontinence | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Gingival pain | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Mouth ulceration | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Chest discomfort | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Infected skin ulcer | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA 26.1 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Blood calcium decreased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Sacral pain | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Restless legs syndrome | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Distractibility | Psychiatric disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Perineal pain | Reproductive system and breast disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Systematic Assessment |
|
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 18002430127 | clintriage.rdg@boehringer-ingelheim.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 28, 2017 | May 29, 2024 | SAP_001.pdf |
| ID | Term |
|---|---|
| D064129 | Prostatic Neoplasms, Castration-Resistant |
| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C588089 | xentuzumab |
| C540278 | enzalutamide |
Not provided
Not provided
Not provided
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| OG001 | Phase II: 160 mg Enzalutamide | Four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Phase II part. |
|
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| Units | Counts |
|---|---|
| Participants |
|
|
| OG001 | Phase II: 160 mg Enzalutamide | Four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Phase II part. |
|
|
|
|
|
|
| OG001 | Phase II: 160 mg Enzalutamide | Four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Phase II part. |
|
|
|
| OG001 | Phase II: 160 mg Enzalutamide | Four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Phase II part. |
|
|
| OG001 | Phase II: 160 mg Enzalutamide | Four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Phase II part. |
|
|
| OG001 | Phase II: 160 mg Enzalutamide | Four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Phase II part. |
|
|
| OG001 | Phase II: 160 mg Enzalutamide | Four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Phase II part. |
|
|
|
| OG001 | Phase II: 160 mg Enzalutamide | Four liquid-filled soft gelatin capsules of 40mg (total: 160mg) enzalutamide administered orally once daily during each 28-day cycle of treatment until disease progression or occurrence of undue toxicities. Phase II part. |
|
|
| Units | Counts |
|---|---|
| Participants |
|
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|