Phase 1
N=7
BI 6727 (Volasertib) Human ADME Trial in Various Solid Tumours
Neoplasms
Bottom Line
View on ClinicalTrials.gov: NCT01145885 ↗Enrolled (actual)
7
Serious AEs
11.5%
Results posted
Jan 2019
Primary outcome: Primary: Individual Time Course Profiles of 14C-radioactivity in Whole Blood and Plasma: Cmax of 14C Labelled Volasertib — 1746; 1150 nmol/L
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- BI 6727 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Male
- Sponsor
- Boehringer Ingelheim
- Primary completion
- Nov 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Individual Time Course Profiles of 14C-radioactivity in Whole Blood and Plasma: Cmax of 14C Labelled Volasertib |
1746; 1150 | — |
| PRIMARY Individual Time Course Profiles of 14C-radioactivity in Urine: Cumulative Fraction of 14C-ratioactivity Excreted in Urine |
4.21; 11.7; 15.6; 18.1 | — |
| PRIMARY Individual Time Course Profiles of 14C-radioactivity in Faeces: Cumulative Fraction of 14C-radioactivity Excreted in Faeces |
0.680; 24.4; 36.7; 42.5 | — |
| PRIMARY Individual Time Course Profiles of Volasertib and CD 10899 in Plasma: Cmax of Volasertib and CD 10899 (a Metabolite of Volasertib). |
926; 9.92 | — |
| PRIMARY Individual Time Course Profile of Volasertib in Urine:Cumulative Fraction of Volasertib Excreted in Urine |
3.24; 7.57; 9.14; 9.89 | — |
| PRIMARY Individual Time Course Profile of CD 10899 in Urine: Cumulative Amount of CD 10899 Excreted in Urine |
1240; 5670; 7580; 8490 | — |
| PRIMARY 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. |
18.1; 42.5 | — |
| PRIMARY Cmax of Volasertib and CD 10899 in Plasma |
926; 11.1 | — |
| PRIMARY AUC0-inf of Volasertib and CD10899 in Plasma |
11400; 1500 | — |
| PRIMARY CL/R of Volasertib and CD 10899 in Urine |
68.5; 102 | — |
| PRIMARY Ae(0-tz) of Volasertib and CD 10899 in Urine |
45800; 8490 | — |
| PRIMARY AUC0-tz of 14C Radioactivity in Plasma and Whole Blood |
4450; 8810 | — |
| PRIMARY Ae(0-tz) of 14C Radioactivity in Urine |
84000 | — |
| PRIMARY Ae,Faeces(0-tz) of 14C Radioactivity |
197000 | — |
| PRIMARY Time Dependency of Cblood Cells/Cplasma Ratio and Cblood/Cplasma Ratio of 14C-radioactivity |
1.52; 1.54; 2.66; 2.76 | — |
| PRIMARY Elucidation of Metabolite Structures and Identification of Major Metabolites in Plasma, Urine, and Faeces |
— | — |
| SECONDARY Percentage of Participants With Drug Related Adverse Events |
100.0; 100.0; 100.0 | — |
| SECONDARY Percentage of Participants With Clinically Relevant Abnormalities for Clinical Assessments, ECG, Vital Signs and Laboratory Tests |
0.0; 0.0; 0.0 | — |
| SECONDARY Percentage of Participants With Clinical Benefit |
42.9; 0.0; 0.0; 57.1; 0.0; 0.0 | — |
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 = =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
Data sourced from ClinicalTrials.gov (NCT01145885). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.