Clinical trial NCT01145885: BI 6727 (Volasertib) Human ADME Trial in Various Solid Tumours
Official title: Investigation of the Metabolism, Excretion and Pharmacokinetics of an Openlabel Single Dose of 300 mg [14C]Volasertib Administered Intravenously in Patients With Various Solid Tumours With a Possible Extension Phase With Nonlabelled Drug
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2010-06-17
Enrollment: 7
Sex: MALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Investigation of absorption, distribution, metabolism and excretion (ADME) and assessment of safety, tolerability and preliminary therapeutic effects of \[14C\]volasertib in patients with advanced solid tumours.


Eligibility criteria: Inclusion criteria:

* Inclusion Criteria 1. Patients with histologically or cytologically confirmed diagnosis of advanced, non resectable and / or metastatic solid tumour
* Inclusion Criteria 2. Male
* Inclusion Criteria 3. Age \>=18 and =\<70 years
* Inclusion Criteria 4. Written informed consent
* Inclusion Criteria 5. Eastern Cooperative Oncology Group (ECOG) performance score =\<2
* Inclusion Criteria 6. Recovery from Common Terminology Criteria for Adverse Events (CTCAE) Grade \>=2 therapy-related toxicities from previous chemo-, hormone-, immuno-, or radiotherapy

Exclusion criteria:

* Exclusion Criteria 1. Serious concomitant non-oncological disease considered by the investigator
* Exclusion Criteria 2. Active infectious disease
* Exclusion Criteria 3. Viral hepatitis, Human Immunodeficiency Virus (HIV) infection
* Exclusion Criteria 4. Clinical evidence of active brain metastasis during the past 6 months
* Exclusion Criteria 5. Second malignancy currently requiring active therapy
* Exclusion Criteria 6. Absolute neutrophil count less than 1,500/mm3
* Exclusion Criteria 7. Platelet count less than 100,000/mm3
* Exclusion Criteria 8. Total bilirubin greater than 1.5 mg/dL
* Exclusion Criteria 9. Aspartate amino transferase (AST) and / or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (if related to liver metastases greater than five times the upper limit of normal)
* Exclusion Criteria 10. Serum creatinine greater than 1.5x Upper Limit of Normal (ULN).
* Exclusion Criteria 11. Known history of QT/QTcF-prolongation
* Exclusion Criteria 12. Patients who are sexually active and having a partner with childbearing potential and unwilling to use a medically acceptable method of contraception
* Exclusion Criteria 13. Treatment with other investigational drugs or participation in another clinical trial
* Exclusion Criteria 14. Chemo-, radio- immuno-, or molecular-targeted cancer-therapy within the past four weeks prior to start of therapy or concomitantly with this trial. This restriction does not apply to steroids and bisphosphonates.
* Exclusion Criteria 15. Alcohol abuse
* Exclusion Criteria 16. Life expectancy less than 12 weeks
* Exclusion Criteria 17. Potent Cytochrome P450 enzyme (CYP) 3A4 and P-glycoprotein inhibitors or inducers
* Exclusion Criteria 18. History of allergy/hypersensitivity

Primary outcomes:
measure: Individual Time Course Profiles of 14C-radioactivity in Whole Blood and Plasma: Cmax of 14C Labelled Volasertib
timeFrame: Whole blood: Pre-dose (-0.5 hours (h)) and 1.0h, 1.983h, 4h, 6h, 8h and 24h after start of the 2h drug infusion.Plasma: Pre-dose (-0.5h) and 1.0h, 1.983h, 4h, 6h, 8h, 24h,48h. 96h, 168h and 336h after start of drug infusion.
measure: Individual Time Course Profiles of 14C-radioactivity in Urine: Cumulative Fraction of 14C-ratioactivity Excreted in Urine
timeFrame: Every 24 hours, up to 504 hours
measure: Individual Time Course Profiles of 14C-radioactivity in Faeces: Cumulative Fraction of 14C-radioactivity Excreted in Faeces
timeFrame: Every 24 hours, up to 504 hours
measure: Individual Time Course Profiles of Volasertib and CD 10899 in Plasma: Cmax of Volasertib and CD 10899 (a Metabolite of Volasertib).
timeFrame: Plasma: Pre-dose (-0.5h) and 1.0h, 1.983h, 4h, 6h, 8h, 24h,48h. 96h, 168h and 336h after start of drug infusion.
measure: Individual Time Course Profile of Volasertib in Urine:Cumulative Fraction of Volasertib Excreted in Urine
timeFrame: Every 24 hours, up to 504 hours
measure: Individual Time Course Profile of CD 10899 in Urine: Cumulative Amount of CD 10899 Excreted in Urine
timeFrame: Every 24 hours, up to 504 hours
measure: Rate and Extent of Excretion Mass Balance Based on the Total Radioactivity in Urine and Faeces: Cumulative Fraction of Excretion 504 Hours After Start of Drug Infusion.
timeFrame: up to 504 hours
measure: Cmax of Volasertib and CD 10899 in Plasma
timeFrame: 30 minutes (min) before start of infusion and 1 hour (h), 1h 59min, 4h, 6h, 8h, 24h, 48h, 96h, 168h and 336h after start of infusion
measure: AUC0-inf of Volasertib and CD10899 in Plasma
timeFrame: 30 minutes (min) before start of infusion and 1 hour (h), 1h 59min, 4h, 6h, 8h, 24h, 48h, 96h, 168h and 336h after start of infusion
measure: CL/R of Volasertib and CD 10899 in Urine
timeFrame: Every 24 hours, up to 504 hours
measure: Ae(0-tz) of Volasertib and CD 10899 in Urine
timeFrame: Every 24 hours, up to 504 hours
measure: AUC0-tz of 14C Radioactivity in Plasma and Whole Blood
timeFrame: 30 minutes (min) before start of infusion and 1 hour (h), 1h 59min, 4h, 6h, 8h, 24h, 48h, 96h, 168h and 336h after start of infusion for plasma; 30 min before start of infusion and 1h, 1h 59min, 4h, 6h, 8h and 24h after start of infusion for whole blood
measure: Ae(0-tz) of 14C Radioactivity in Urine
timeFrame: Every 24 hours, up to 504 hours
measure: Ae,Faeces(0-tz) of 14C Radioactivity
timeFrame: Every 24 hours, up to 504 hours
measure: Time Dependency of Cblood Cells/Cplasma Ratio and Cblood/Cplasma Ratio of 14C-radioactivity
timeFrame: 1.983 hours and 6 hours
measure: Elucidation of Metabolite Structures and Identification of Major Metabolites in Plasma, Urine, and Faeces
timeFrame: 3 weeks
Secondary outcomes:
measure: Percentage of Participants With Drug Related Adverse Events
timeFrame: From first intake of study drug until 21 days after last intake of the study drug, up to 63 days
measure: Percentage of Participants With Clinically Relevant Abnormalities for Clinical Assessments, ECG, Vital Signs and Laboratory Tests
timeFrame: From first intake of study drug until 21 days after last intake of the study drug, up to 63 days
measure: Percentage of Participants With Clinical Benefit
timeFrame: 21, 42 and 63 days
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: 1230.23.36001 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: