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

Prostatic Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02182219
• Other study ID #: 1199.4
• Status: Completed
• Phase: Phase 1
• First received: July 2, 2014
• Last updated: July 17, 2014
• Start date: November 2005

Study information

• Verified date: July 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. primary completion date: April 2007
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostatic Neoplasms

Intervention

Drug:
• BIBF 1120

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD)		Up to day 126	No
Primary	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	No
Secondary	Area under the plasma concentration-time curve (AUC) over the dosing interval t following the first dose (AUC0-24)		up to 336 hours after drug administration	No
Secondary	Incidence of prostate specific antigen (PSA) decline = 50% from the baseline value		Baseline, up to day 126	No
Secondary	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	No
Secondary	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	No
Secondary	Change in Eastern Cooperative Oncology Group (ECOG) performance score		Baseline, up to day 156	No
Secondary	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 t		up to 336 hours after drug administration	No
Secondary	AUC over the time interval from zero extrapolated to infinity (AUC0-8) after the first dose		up to 336 hours after drug administration	No
Secondary	Percentage of AUC0-8 obtained by extrapolation (%AUCtz-8)		up to 336 hours after drug administration	No
Secondary	Maximum measured plasma concentration (Cmax) following the first dose		up to 336 hours after drug administration	No
Secondary	Time from dosing to the maximum plasma concentration (tmax) following the first dose		up to 336 hours after drug administration	No
Secondary	Terminal rate constant in plasma (?z )		up to 336 hours after drug administration	No
Secondary	Terminal half-life (t1/2)		up to 336 hours after drug administration	No
Secondary	Mean residence time (MRTpo) after oral administration		up to 336 hours after drug administration	No
Secondary	Apparent clearance (CL/F)		up to 336 hours after drug administration	No
Secondary	Apparent volume of distribution during the terminal phase (Vz/F)		up to 336 hours after drug administration	No
Secondary	Pre-dose plasma concentration immediately before administration		Days 2, 3, 8 and 15	No
Secondary	Plasma concentration at 24 hours following the first (C24,1) dose		24 hours after administration	No
Secondary	Mean residence time (MRTiv) after i.v. administration		up to 336 hours after drug administration	No
Secondary	Clearance (CL) after i.v. administration		up to 336 hours after drug administration	No
Secondary	Apparent volume of distribution during the terminal phase (Vz) after i.v. administration		up to 336 hours after drug administration	No
Secondary	Apparent volume of distribution at steady state (Vss)		up to 336 hours after drug administration	No

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