Clinical Trials List
Protocol Number1280.8
NCT Number(ClinicalTrials.gov Identfier)NCT02204072
2015-12-08 - 2018-08-30
Phase II
Terminated4
ICD-9185
Malignant neoplasm of prostate
A Phase Ib/II, Multicentre, Open Label, Randomised 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
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Trial Applicant
Boehringer Ingelheim
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Sponsor
Boehringer Ingelheim
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 洪啟峰 Division of Urology
- Cheng-Kuang Yang Division of Urology
- 熊小澐 Division of Urology
- Chuan-Shu Chen Division of Urology
- Jian-Ri Li Division of Urology
- 林萬鈺 Division of Urology
- Cheng-Che Chen Division of Urology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 朱力行 Division of Urology
- Yi-Hsiu Huang Division of Urology
- William Huang Division of Urology
- 沈書慧 Division of Urology
- Tzu-Ping Lin Division of Urology
- Hsiao-Jen Chung Division of Urology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Wen-Pin Su Division of Hematology & Oncology
- Wu-Chou Su Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- Yeong-Shiau Pu Division of Hematology & Oncology
- - - Division of Hematology & Oncology
- Yu-Chieh Tsai Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
castration-resistant prostate cancer, CRPC
Objectives
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).
Test Drug
BI 836845
Active Ingredient
fully human IgG1 monoclonal antibody (mAb)
Dosage Form
Injection
Dosage
200
Endpoints
Criteria for efficacy, pharmacokinetics pharmacodynamics & pharmacogenomics:
Phase Ib Expansion Cohort
Primary Endpoint:
PSA response
Secondary Endpoints:
Radiological progression free survival (PFS) based on investigator
assessment
Changes in circulating tumour cells (CTC) response – CTC reduction
Phase II Randomised Trial
Primary Endpoint :
Radiological progression free survival (PFS) based on central review
Secondary Endpoints:
Overall survival
Time to PSA progression
Maximum decline in PSA
Percentage change in PSA at week 12
PSA response
Changes in circulating tumour cells (CTC) response – CTC reduction
Criteria for safety:
Phase Ib Escalation
Primary Endpoint
Number of patients with Dose Limiting Toxicities
Maximum Tolerated Dose (MTD) of BI 836845
Phase Ib Expansion Cohort
Primary Endpoint:
PSA response
Secondary Endpoints:
Radiological progression free survival (PFS) based on investigator
assessment
Changes in circulating tumour cells (CTC) response – CTC reduction
Phase II Randomised Trial
Primary Endpoint :
Radiological progression free survival (PFS) based on central review
Secondary Endpoints:
Overall survival
Time to PSA progression
Maximum decline in PSA
Percentage change in PSA at week 12
PSA response
Changes in circulating tumour cells (CTC) response – CTC reduction
Criteria for safety:
Phase Ib Escalation
Primary Endpoint
Number of patients with Dose Limiting Toxicities
Maximum Tolerated Dose (MTD) of BI 836845
Inclution Criteria
Inclusion criteria
1. The patient has histologically, or cytologically, confirmed adenocarcinoma of the
prostate.
2. Male patient aged ≥ 18 years old.
3. 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.
4. Patients with a PSA ≥ 20 ng/mL.
5. 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.
6. Eastern Cooperative Oncology Group performance status (ECOG PS) 0, 1 or 2.
7. Cardiac left ventricular function with resting ejection fraction >50% as determined by
ECHO or MUGA.
8. Absolute neutrophil count (ANC) ≥1500/uL.
9. Haemoglobin ≥9 g/dL.
10. Platelets ≥100,000/uL.
11. Bilirubin ≤ 1.5 times the upper limit of normal (ULN).
12. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 times the ULN
(or ≤ 5 times the ULN if liver metastases are present).
13. Creatinine ≤ 1.5 x ULN.
14. International normalized ratio (INR) ≤ 1.4 and a partial thromboplastin time (PTT) ≤ 5
seconds above the ULN (unless on oral anticoagulant therapy). Patients receiving fulldose 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).
15. Fasting plasma glucose < 8.9 mmol/L (< 160 mg/dL) and HbA1c < 8.0%.
Inclusion criteria only for patients entering phase Ib dose escalation and phase II:
16. 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.
17. Patients who have disease progression during, or after, receiving abiraterone treatment
in any setting.
18. Patients must have progressive disease defined as at least one of the following:
a. Progressive measurable disease: using conventional solid tumour criteria
RECIST 1.1.
b. Bone scan progression: at least two new lesions on bone scan, plus a rising
PSA as described in c below.
c. 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:
19. 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.
20. Archive tumour tissue is available prior to recruitment for pharmacogenomic tests.
1. The patient has histologically, or cytologically, confirmed adenocarcinoma of the
prostate.
2. Male patient aged ≥ 18 years old.
3. 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.
4. Patients with a PSA ≥ 20 ng/mL.
5. 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.
6. Eastern Cooperative Oncology Group performance status (ECOG PS) 0, 1 or 2.
7. Cardiac left ventricular function with resting ejection fraction >50% as determined by
ECHO or MUGA.
8. Absolute neutrophil count (ANC) ≥1500/uL.
9. Haemoglobin ≥9 g/dL.
10. Platelets ≥100,000/uL.
11. Bilirubin ≤ 1.5 times the upper limit of normal (ULN).
12. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 times the ULN
(or ≤ 5 times the ULN if liver metastases are present).
13. Creatinine ≤ 1.5 x ULN.
14. International normalized ratio (INR) ≤ 1.4 and a partial thromboplastin time (PTT) ≤ 5
seconds above the ULN (unless on oral anticoagulant therapy). Patients receiving fulldose 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).
15. Fasting plasma glucose < 8.9 mmol/L (< 160 mg/dL) and HbA1c < 8.0%.
Inclusion criteria only for patients entering phase Ib dose escalation and phase II:
16. 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.
17. Patients who have disease progression during, or after, receiving abiraterone treatment
in any setting.
18. Patients must have progressive disease defined as at least one of the following:
a. Progressive measurable disease: using conventional solid tumour criteria
RECIST 1.1.
b. Bone scan progression: at least two new lesions on bone scan, plus a rising
PSA as described in c below.
c. 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:
19. 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.
20. Archive tumour tissue is available prior to recruitment for pharmacogenomic tests.
Exclusion Criteria
Exclusion criteria
1. Exclusion criterion 1 is not applicable for patients enrolled after protocol version 3 (or
subsequent versions) are approved.
2. Exclusion criterion 2 is not applicable for patients enrolled after protocol version 3 (or
subsequent versions) are approved.
3. Prior therapy with agents targeting IGF and/or IGFR pathway.
4. Patients that have been treated with any of the following within 4 weeks of starting
trial treatment: chemotherapy, immunotherapy, biological therapies, molecular
targeted therapy, hormone therapy (except LHRH agonists), 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).
5. Use of any investigational drug within 4 weeks before start of trial treatment or
concomitantly with this trial.
6. Patients that have been treated with strong CYP2C8 inhibitors, CYP2C8 inducers,
within 2 weeks of starting the trial treatment.
7. 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.
8. Patients with small cell or neuroendocrine tumours.
9. Patients with known or suspected leptomeningeal metastases.
10. Uncontrolled or poorly controlled hypertension.
11. Patients with poorly controlled diabetes mellitus. Patients with a history of diabetes
are allowed to participate, provided that their blood glucose is within normal range
(fasting < 160 mg/dL or below ULN) and that they are on a stable dietary or
therapeutic regimen for this condition.
12. Known human immunodeficiency virus infection or acquired immunodeficiency
syndrome-related illness.
13. Patients with epilepsy, seizures, or predisposing factors for seizure as judged by the
investigator.
14. Patients unable to comply with the protocol as judged by the investigator.
15. Active alcohol or active drug abuse as judged by the investigator.
16. A history of allergy to human monoclonal antibodies.
17. 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.
Exclusion criteria only for patients entering phase Ib dose escalation and phase II:
18. Patients that have received prior enzalutamide in any setting will not be eligible.
Exclusion criterion only for patients entering phase Ib expansion cohort:
19. 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:
20. 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.
After approval of protocol version 3 (or subsequent versions) the additional following
exclusion criteria apply:
For all patients:
21. Previous or concomitant malignancies at any other site with the exception of the
following:
a.) benign basal cell carcinoma
b.) benign low grade transitional cell carcinoma of the bladder
c.) 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:
22. Patients who have received more than 2 prior non-docetaxel-containing cytotoxic
chemotherapy regimens for Metastatic Castration-Resistant Prostate Cancer
(mCRPC).
23. Patients who have received a taxane based treatment or abiraterone, within 4 weeks
before start of study treatment.
1. Exclusion criterion 1 is not applicable for patients enrolled after protocol version 3 (or
subsequent versions) are approved.
2. Exclusion criterion 2 is not applicable for patients enrolled after protocol version 3 (or
subsequent versions) are approved.
3. Prior therapy with agents targeting IGF and/or IGFR pathway.
4. Patients that have been treated with any of the following within 4 weeks of starting
trial treatment: chemotherapy, immunotherapy, biological therapies, molecular
targeted therapy, hormone therapy (except LHRH agonists), 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).
5. Use of any investigational drug within 4 weeks before start of trial treatment or
concomitantly with this trial.
6. Patients that have been treated with strong CYP2C8 inhibitors, CYP2C8 inducers,
within 2 weeks of starting the trial treatment.
7. 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.
8. Patients with small cell or neuroendocrine tumours.
9. Patients with known or suspected leptomeningeal metastases.
10. Uncontrolled or poorly controlled hypertension.
11. Patients with poorly controlled diabetes mellitus. Patients with a history of diabetes
are allowed to participate, provided that their blood glucose is within normal range
(fasting < 160 mg/dL or below ULN) and that they are on a stable dietary or
therapeutic regimen for this condition.
12. Known human immunodeficiency virus infection or acquired immunodeficiency
syndrome-related illness.
13. Patients with epilepsy, seizures, or predisposing factors for seizure as judged by the
investigator.
14. Patients unable to comply with the protocol as judged by the investigator.
15. Active alcohol or active drug abuse as judged by the investigator.
16. A history of allergy to human monoclonal antibodies.
17. 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.
Exclusion criteria only for patients entering phase Ib dose escalation and phase II:
18. Patients that have received prior enzalutamide in any setting will not be eligible.
Exclusion criterion only for patients entering phase Ib expansion cohort:
19. 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:
20. 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.
After approval of protocol version 3 (or subsequent versions) the additional following
exclusion criteria apply:
For all patients:
21. Previous or concomitant malignancies at any other site with the exception of the
following:
a.) benign basal cell carcinoma
b.) benign low grade transitional cell carcinoma of the bladder
c.) 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:
22. Patients who have received more than 2 prior non-docetaxel-containing cytotoxic
chemotherapy regimens for Metastatic Castration-Resistant Prostate Cancer
(mCRPC).
23. Patients who have received a taxane based treatment or abiraterone, within 4 weeks
before start of study treatment.
The Estimated Number of Participants
-
Taiwan
22 participants
-
Global
120 participants
