An Open Phase I Single Dose Escalation Study of BI 2536 BS Administered Intravenously in Patients With Advanced Solid Tumours With Repeated Administration in Patients With Clinical Benefit

Boehringer Ingelheim0 sites63 target enrollmentAugust 2004

ConditionsNeoplasms

InterventionsBI 2536 BS, intravenous

DrugsBI 2536 BS, intravenous

Overview

Phase: Phase 1
Intervention: BI 2536 BS, intravenous
Conditions: Neoplasms
Sponsor: Boehringer Ingelheim
Enrollment: 63
Primary Endpoint: Maximum tolerated dose (MTD) for a single dose of BI 2536 BS
Status: Completed
Last Updated: 11 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

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

Registry

clinicaltrials.gov

Start Date

August 2004

End Date

March 2007

Last Updated

11 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Boehringer Ingelheim

Responsible Party

Sponsor

Eligibility Criteria

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)

Arms & Interventions

Treatment B

BI 2536 BS multiple rising doses on three consecutive days (d1-3 schedule)

Intervention: BI 2536 BS, intravenous

Treatment A

BI 2536 BS single rising dose

Intervention: BI 2536 BS, intravenous

Outcomes

Primary Outcomes

Maximum tolerated dose (MTD) for a single dose of BI 2536 BS

Time Frame: Up to 16 weeks

MTD for single doses of BI 2536 BS on 3 consecutive days

Time Frame: Up to 16 weeks

Secondary Outcomes

Time from dosing to maximum concentration of BI 2536 BS in plasma (tmax)(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)
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)
Terminal rate constant in plasma (λz)(Pre-dose, up to 216 hours after drug administration)
Total clearance of BI 2536 BS in the plasma after intravascular administration (CL)(Pre-dose, up to 216 hours after drug administration)
Maximum concentration of BI 2536 BS analyte in plasma (Cmax)(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)
Number of patients with adverse events(Up to 1 year)
Mean residence time of BI 2536 BS in the body after intravenous administration (MRT)(Pre-dose, up to 216 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)
Assessment of objective treatment response by tumour measurements(Up to 1 year)
Percentage of the AUC0-∞ that is obtained by extrapolation (%AUC0-tz)(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)
Apparent volume of distribution at steady state following intravascular administration (Vss)(Pre-dose, up to 216 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)