Clinical trial NCT02363855: Phase 1 Dose Escalation Study of BAY 1841788 in Japanese Metastatic Castration-resistant Prostate Cancer (mCRPC) Subjects
Official title: An Open Label Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BAY 1841788 in Japanese Subjects With Metastatic Castration-resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prostatic Neoplasms
Keywords: Neoplasm Metastasis
Metastatic castration-resistant prostate cancer
Castration-resistant prostate cancer (CRPC)
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2015-02-16
Enrollment: 9
Sex: MALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objectives of this study are to investigate the safety and tolerability of BAY 1841788 in Japanese subjects with metastatic castration-resistant prostate cancer (mCRPC) and the PK of BAY 1841788 and its major metabolite BAY 1896953.

Detailed description: The drug product is licensed from Orion pharma, Finland which is also the manufacturer of the product.

Eligibility criteria: Inclusion Criteria:

* Japanese males aged ≥ 20 years
* Histologically or cytologically confirmed adenocarcinoma of prostate without neuroendocrine differentiation or small cell features
* Patients with metastatic castration-resistant prostate cancer (mCRPC). CRPC is defined as follows

  * Ongoing androgen deprivation therapy with a luteinizing hormone-releasing hormone (LHRH) analogue or antagonist, or bilateral orchiectomy, and castrate level of serum testosterone (\< 1.7 nmol/l \[50 ng/dL\]) at screening AND
  * Progressive disease and/or prostate-specific antigen (PSA) increase of three consecutive rises, at least 1 week apart AND
  * PSA \> 2ng/mL at screening
* Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1
* Life expectancy of at least 3 months
* Blood counts at screening: haemoglobin ≥ 9.0 g/dL, absolute neutrophil count ≥ 1,500/μL (1.5x109/l), platelet count ≥ 100,000/μL (100x109/l) (patient must not have received any growth factor or blood transfusion within 7 days of the hematology laboratory obtained at screening)
* Screening values of serum alanine aminotransferase (ALT) and/or aspartate transaminase (AST) ≤ 2.5 x upper limit of normal (ULN), total bilirubin ≤ 1.5 x ULN, creatinine ≤ 1.5 x ULN, albumin \> 3.0 g/dl
* Prior treatment with antiandrogen. Discontinuation of bicalutamide or nilutamide (not approved in Japan) at least 6 weeks and other antiandrogens at least 4 weeks prior to the start of the study drug administration.

Exclusion Criteria:

* Known metastases in the brain
* Symptomatic local-regional disease that requires medical intervention including moderate/severe urinary obstruction or hydronephrosis due to prostate cancer
* Acute toxicities (except for alopecia and CTCAE grade 2 neuropathy) of prior treatments and procedures not resolved to CTCAE ≤ grade 1 or baseline before the first drug administration
* Febrile neutropenia of Common Terminology Criteria for Adverse Events (CTCAE) ≥ 3
* History of other malignancy within the previous 5 years except a basal cell carcinoma of skin and any other cancer for which treatment has been completed ≥ 5 years ago and from which the patient has been disease-free5 years ago and from which the patient has been disease-free
* Prior treatment within 4 weeks before the first drug administration with immunotherapy, antiandrogen, CYP17 inhibitor (CYP17i), oral ketoconazole, estrogens, 5-α reductase inhibitors or investigational treatment
* Use of bicalutamide or nilutamide (not approved in Japan) within 6 weeks before the first drug administration
* Radiation therapy (external beam radiation therapy \[EBRT\], brachytherapy, or radiopharmaceuticals) or chemotherapy (except for nitrosoureas and mitomycin C) within 4 weeks before the first drug administration. Use of nitrosoureas or mitomycin C within 6 weeks before the first drug administration.
* Prior use of any herbal products known to decrease PSA levels (e.g. PC SPES or saw palmetto) within 4 weeks before the first drug administration

Primary outcomes:
measure: Number of participants with Treatment Emergent Adverse Event as measure of safety and tolerability
timeFrame: Up to 12 weeks
measure: The intensity of an adverse event graded using the NCI CTCAE version 4.03
timeFrame: Up to 12 weeks
measure: Plasma concentration of BAY 1841788 characterized by Cmax
timeFrame: Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
measure: Plasma concentration of BAY 1841788 characterized by tmax
timeFrame: Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
measure: Plasma concentration of BAY 1841788 characterized by AUC(0-12)
timeFrame: Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
measure: Plasma concentration of metabolite BAY 1896953 characterized by Cmax
timeFrame: Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
measure: Plasma concentration of metabolite BAY 1896953 characterized by tmax
timeFrame: Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
measure: Plasma concentration of metabolite BAY 1896953 characterized by AUC(0-12)
timeFrame: Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
measure: Plasma concentration of diastereomers BAY 1896951 characterized by Cmax
timeFrame: Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
measure: Plasma concentration of diastereomers BAY 1896951 characterized by tmax
timeFrame: Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
measure: Plasma concentration of diastereomers BAY 1896951 characterized by AUC(0-12)
timeFrame: Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
measure: Plasma concentration of diastereomers BAY 1896952 characterized by Cmax
timeFrame: Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
measure: Plasma concentration of diastereomers BAY 1896952 characterized by tmax
timeFrame: tmax: time to reach maximum drug concentration in plasma after single (first) dose
measure: Plasma concentration of diastereomers BAY 1896952 characterized by AUC(0-12)
timeFrame: Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
Secondary outcomes:
Other outcomes:
Locations:
city: Kashiwa
country: Japan
state: Chiba
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: