Oral Treatment With BIBF 1120 Together With Docetaxel and Prednisone in Patients With Hormone Refractory Prostate Cancer

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

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.

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