Oral Treatment With BIBF 1120 Together With Docetaxel and Prednisone in Patients With Hormone Refractory Prostate Cancer
- Registration Number
- NCT02182219
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
The primary objective of this study was to determine the safety and Maximum tolerated dose (MTD) of BIBF 1120 combination therapy with docetaxel and prednisone in patients with hormone refractory prostate cancer. Secondary objectives were to characterise the pharmacokinetic profiles of BIBF 1120 and docetaxel and possible Pharmacokinetic (PK) interactions between BIBF 1120 and docetaxel and to obtain preliminary information on anti-tumour activity.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 21
Inclusion Criteria
-
Patients with histologically-proven metastatic prostate adenocarcinoma
-
Progression after hormonal therapy
-
Progressive disease as follows:
- Increase of PSA > 5 ng/ml on two occasions despite castrate levels of testosterone before screening
- AND/OR Progressive measurable disease (RECIST criteria)
- AND/OR Progressive bone metastases (presence of new lesion(s) on a bone scan)
-
Life expectancy of at least three months
-
ECOG performance status ≤ 2
-
Patient written informed consent obtained prior to any trial procedures and that is consistent with ICH-GCP (International Conference on Harmonization - Good Clinical Practice) guidelines.
Exclusion Criteria
- Prior treatment for hormone refractory prostate cancer (HRPC) including chemotherapy, biologic response modifier therapy, or any investigational drug
- Participation in another clinical study within the past four weeks before start of therapy or concomitantly with this study
- Major injuries and surgeries within the past 4 weeks. Planned surgical procedures during the trial
- Brain metastases
- Radiotherapy superior to 30% of the medullar volume
- Other malignancy diagnosed within the past 5 years (other than non-melanomatous skin cancer)
- Gastrointestinal abnormalities that would interfere with intake or absorption of the study drug, such as a requirement for intravenous alimentation, prior surgical procedures affecting absorption, treatment for peptic ulcer disease within the last 6 months, active gastrointestinal bleeding unrelated to cancer (as evidenced by either hematemesis, or melena in the past 3 months and without endoscopic documented resolution), or malabsorption syndromes
- Previous history of stroke, angor pectoris, ischemic cardiomyopathy, cerebral ischemia, arteritis in the past 6 months
- Recent history of hemorrhagic or evolutive thrombotic event (including transient ischemic attacks) in the past 6 months
- Patients who require full-dose anticoagulation or heparinization
- Absolute neutrophil count (ANC) < 1,500/μl, platelet count < 100,000/μl, or hemoglobin < 8 mg/dL
- Total bilirubin > upper limit of normal (ULN); alanine amino transferase (ALT) and/or aspartate amino transferase (AST) >1.5 X ULN
- Serum creatinine > 1.5 mg/dL (> 132 μ mole/L, SI Unit equivalent)
- Known or suspected active alcohol or drug abuse
- Patients unable to comply with the protocol
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description BIBF 1120 BIBF 1120 -
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose (MTD) Up to day 126 Incidence and intensity of Adverse Events according to the Common Terminology Criteria for Adverse Events (version 3.0) associated with increasing doses of BIBF 1120 up to 6 months
- Secondary Outcome Measures
Name Time Method Apparent volume of distribution during the terminal phase (Vz) after i.v. administration up to 336 hours after drug administration Apparent volume of distribution at steady state (Vss) up to 336 hours after drug administration Number of patients without signs of tumour progression (stable disease (SD)) according to RECIST criteria Baseline, day 15 of cycle 3 and at the end of cycle 6 Maximum measured plasma concentration (Cmax) following the first dose up to 336 hours after drug administration Time from dosing to the maximum plasma concentration (tmax) following the first dose up to 336 hours after drug administration Terminal half-life (t1/2) up to 336 hours after drug administration Apparent clearance (CL/F) up to 336 hours after drug administration Area under the plasma concentration-time curve (AUC) over the dosing interval τ following the first dose (AUC0-24) up to 336 hours after drug administration Number of patients with an objective tumour response (Partial Response (PR), Complete Response (CR)) according to Response Evaluation Criteria In Solid Tumours (RECIST) criteria Baseline, day 15 of cycle 3 and at the end of cycle 6 AUC over the time interval from zero to the time of the last quantifiable drug concentration after the first dose (AUC0-tz) within the dosing interval τ up to 336 hours after drug administration Percentage of AUC0-∞ obtained by extrapolation (%AUCtz-∞) up to 336 hours after drug administration Terminal rate constant in plasma (λz ) up to 336 hours after drug administration Apparent volume of distribution during the terminal phase (Vz/F) up to 336 hours after drug administration Pre-dose plasma concentration immediately before administration Days 2, 3, 8 and 15 Mean residence time (MRTiv) after i.v. administration up to 336 hours after drug administration Change in Eastern Cooperative Oncology Group (ECOG) performance score Baseline, up to day 156 Incidence of prostate specific antigen (PSA) decline ≥ 50% from the baseline value Baseline, up to day 126 Mean residence time (MRTpo) after oral administration up to 336 hours after drug administration Clearance (CL) after i.v. administration up to 336 hours after drug administration AUC over the time interval from zero extrapolated to infinity (AUC0-∞) after the first dose up to 336 hours after drug administration Plasma concentration at 24 hours following the first (C24,1) dose 24 hours after administration