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.

Study Overview

• Status: Completed
• Conditions: Prostatic Neoplasms
• Intervention / Treatment: Drug: BIBF 1120

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIBF 1120	Drug: BIBF 1120

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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
Incidence of prostate specific antigen (PSA) decline ≥ 50% from the baseline value	Baseline, up to day 126
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
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
Change in Eastern Cooperative Oncology Group (ECOG) performance score	Baseline, up to day 156
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
AUC over the time interval from zero extrapolated to infinity (AUC0-∞) after the first dose	up to 336 hours after drug administration
Percentage of AUC0-∞ obtained by extrapolation (%AUCtz-∞)	up to 336 hours after drug administration
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 rate constant in plasma (λz )	up to 336 hours after drug administration
Terminal half-life (t1/2)	up to 336 hours after drug administration
Mean residence time (MRTpo) after oral administration	up to 336 hours after drug administration
Apparent clearance (CL/F)	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
Plasma concentration at 24 hours following the first (C24,1) dose	24 hours after administration
Mean residence time (MRTiv) after i.v. administration	up to 336 hours after drug administration
Clearance (CL) after i.v. administration	up to 336 hours after drug administration
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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): April 1, 2007

Study Registration Dates

• First Submitted: July 2, 2014
• First Submitted That Met QC Criteria: July 2, 2014
• First Posted (Estimate): July 8, 2014

Study Record Updates

• Last Update Posted (Estimate): July 18, 2014
• Last Update Submitted That Met QC Criteria: July 17, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Nintedanib
• Other Study ID Numbers: 1199.4