Neoplasms
Conditions
Brief summary
The primary objective of this study was to determine the maximum tolerated dose (MTD) of BI 2536 BS in patients with advanced solid tumours. Secondary objectives were the evaluation of safety, efficacy, and pharmacokinetics of BI 2536 BS
Interventions
DRUGBI 2536 BS, intravenous
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with confirmed diagnosis of advanced, non resectable and / or metastatic solid tumours, who had failed conventional treatment, or for whom no therapy of proven efficacy exists, or who were not amenable to established forms of treatment * Evaluable tumour deposits * Age of 18 years or older * Life expectancy of at least 6 months * Written informed consent consistent with international conference of harmonization (ICH) - good clinical practice (GCP) and local legislation * Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score ≤ 2 * And full recovery from all therapy-related toxicities from previous chemo-, hormone-, immuno-, or radiotherapies
Exclusion criteria
* Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the trial protocol * Pregnancy or breastfeeding * Active infectious disease * Known brain metastases * Second malignancy requiring therapy * Absolute neutrophil count less than 1500/mm3 * Platelet count less than 100 000/mm3 * Bilirubin greater than 1.5 mg/dL (\> 26 μmol/L, international system of units (SI) equivalent) * 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) * Serum creatinine greater than 1.5 mg/dL (\> 132 μmol/L, SI unit equivalent) * Sexually active women and men who are unwilling to use a medically acceptable method of contraception * Treatment with other investigational drugs or participation in another clinical trial within the past four weeks before start of therapy or concomitantly with this trial (except for present trial drug) * Chemo-, radio or immunotherapy within the past four weeks before start of therapy or concomitantly with this trial * Patients unable to comply with the trial protocol * Or active alcohol or drug abuse
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose (MTD) for a single dose of BI 2536 BS | Up to 16 weeks |
| MTD for single doses of BI 2536 BS on 3 consecutive days | Up to 16 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum concentration of BI 2536 BS analyte in plasma (Cmax) | Pre-dose, up to 216 hours after drug administration | — |
| Time from dosing to maximum concentration of BI 2536 BS in plasma (tmax) | Pre-dose, up to 216 hours after drug administration | — |
| Area under the concentration-time curve of BI 2536 BS in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) | Pre-dose, up to 216 hours after drug administration | — |
| Percentage of the AUC0-∞ that is obtained by extrapolation (%AUC0-tz) | Pre-dose, up to 216 hours after drug administration | — |
| Terminal rate constant in plasma (λz) | Pre-dose, up to 216 hours after drug administration | — |
| Terminal half-life of BI 2536 BS in plasma (t1/2) | Pre-dose, up to 216 hours after drug administration | — |
| Assessment of objective treatment response by tumour measurements | Up to 1 year | Evaluated according to the response evaluation criteria in solid tumors (RECIST) |
| Total clearance of BI 2536 BS in the plasma after intravascular administration (CL) | Pre-dose, up to 216 hours after drug administration | — |
| Apparent volume of distribution during the terminal phase λz following an intravascular dose (Vz) | Pre-dose, up to 216 hours after drug administration | — |
| Apparent volume of distribution at steady state following intravascular administration (Vss) | Pre-dose, up to 216 hours after drug administration | — |
| Amount of BI 2536 BS that is eliminated in urine from the time point 0 to time point 24/48 (Ae0-24/48) | Pre-dose, up to 48 hours after drug administration | — |
| Fraction of analyte eliminated in urine from time point 0 to time point 24/48 (fe0-24/48) | Pre-dose, up to 48 hours after drug administration | — |
| Renal clearance of BI 2536 BS from the time point 0 to time point 24/48 (CLR,0-24/48) | Pre-dose, up to 48 hours afterdrug administration | — |
| Mean residence time of BI 2536 BS in the body after intravenous administration (MRT) | Pre-dose, up to 216 hours after drug administration | — |
| Number of patients with adverse events | Up to 1 year | — |
Outcome results
None listed