Clinical trial NCT02182219: Oral Treatment With BIBF 1120 Together With Docetaxel and Prednisone in Patients With Hormone Refractory Prostate Cancer
Official title: A Phase I Open Label Dose Escalation Study of Continuous (Except on the Days of Chemotherapy Infusion) Oral Treatment With BIBF 1120 Together With Docetaxel and Prednisone in Patients With Hormone Refractory Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prostatic Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-07-08
Enrollment: 21
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Patients with histologically-proven metastatic prostate adenocarcinoma
2. Progression after hormonal therapy
3. 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)
4. Life expectancy of at least three months
5. ECOG performance status ≤ 2
6. 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:

1. Prior treatment for hormone refractory prostate cancer (HRPC) including chemotherapy, biologic response modifier therapy, or any investigational drug
2. Participation in another clinical study within the past four weeks before start of therapy or concomitantly with this study
3. Major injuries and surgeries within the past 4 weeks. Planned surgical procedures during the trial
4. Brain metastases
5. Radiotherapy superior to 30% of the medullar volume
6. Other malignancy diagnosed within the past 5 years (other than non-melanomatous skin cancer)
7. 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
8. Previous history of stroke, angor pectoris, ischemic cardiomyopathy, cerebral ischemia, arteritis in the past 6 months
9. Recent history of hemorrhagic or evolutive thrombotic event (including transient ischemic attacks) in the past 6 months
10. Patients who require full-dose anticoagulation or heparinization
11. Absolute neutrophil count (ANC) \< 1,500/μl, platelet count \< 100,000/μl, or hemoglobin \< 8 mg/dL
12. Total bilirubin \> upper limit of normal (ULN); alanine amino transferase (ALT) and/or aspartate amino transferase (AST) \>1.5 X ULN
13. Serum creatinine \> 1.5 mg/dL (\> 132 μ mole/L, SI Unit equivalent)
14. Known or suspected active alcohol or drug abuse
15. Patients unable to comply with the protocol

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: Up to day 126
measure: 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
timeFrame: up to 6 months
Secondary outcomes:
measure: Area under the plasma concentration-time curve (AUC) over the dosing interval τ following the first dose (AUC0-24)
timeFrame: up to 336 hours after drug administration
measure: Incidence of prostate specific antigen (PSA) decline ≥ 50% from the baseline value
timeFrame: Baseline, up to day 126
measure: Number of patients with an objective tumour response (Partial Response (PR), Complete Response (CR)) according to Response Evaluation Criteria In Solid Tumours (RECIST) criteria
timeFrame: Baseline, day 15 of cycle 3 and at the end of cycle 6
measure: Number of patients without signs of tumour progression (stable disease (SD)) according to RECIST criteria
timeFrame: Baseline, day 15 of cycle 3 and at the end of cycle 6
measure: Change in Eastern Cooperative Oncology Group (ECOG) performance score
timeFrame: Baseline, up to day 156
measure: 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
timeFrame: up to 336 hours after drug administration
measure: AUC over the time interval from zero extrapolated to infinity (AUC0-∞) after the first dose
timeFrame: up to 336 hours after drug administration
measure: Percentage of AUC0-∞ obtained by extrapolation (%AUCtz-∞)
timeFrame: up to 336 hours after drug administration
measure: Maximum measured plasma concentration (Cmax) following the first dose
timeFrame: up to 336 hours after drug administration
measure: Time from dosing to the maximum plasma concentration (tmax) following the first dose
timeFrame: up to 336 hours after drug administration
measure: Terminal rate constant in plasma (λz )
timeFrame: up to 336 hours after drug administration
measure: Terminal half-life (t1/2)
timeFrame: up to 336 hours after drug administration
measure: Mean residence time (MRTpo) after oral administration
timeFrame: up to 336 hours after drug administration
measure: Apparent clearance (CL/F)
timeFrame: up to 336 hours after drug administration
measure: Apparent volume of distribution during the terminal phase (Vz/F)
timeFrame: up to 336 hours after drug administration
measure: Pre-dose plasma concentration immediately before administration
timeFrame: Days 2, 3, 8 and 15
measure: Plasma concentration at 24 hours following the first (C24,1) dose
timeFrame: 24 hours after administration
measure: Mean residence time (MRTiv) after i.v. administration
timeFrame: up to 336 hours after drug administration
measure: Clearance (CL) after i.v. administration
timeFrame: up to 336 hours after drug administration
measure: Apparent volume of distribution during the terminal phase (Vz) after i.v. administration
timeFrame: up to 336 hours after drug administration
measure: Apparent volume of distribution at steady state (Vss)
timeFrame: up to 336 hours after drug administration
Other outcomes:
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