Dose Escalation Study of BI 2536 BS in Patients With Advanced Solid Tumours With Repeated Administration in Patients With Clinical Benefit

Study Overview
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Brief Summary
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Primary: Maximum tolerated dose (MTD) Secondary: Determination of the pharmacokinetic profile of BI 2536. Assessment of safety and efficacy.

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

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: BI 2536


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients with confirmed diagnosis of advanced, non resectable and/or metastatic solid tumours, who have failed conventional treatment, or for whom no therapy of proven efficacy exists, or who are not amenable to established forms of treatment Evaluable tumour deposits Age 18 years or older Life expectancy of at least six months Written informed consent consistent with international conference of harmonization (ICH) - good clinical practice (GCP) and local legislation Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2 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 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) 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) Women and men who are sexually active and 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 2536<br>single escalating dose, followed by repeated administration in patients with clinical benefit | Drug: BI 2536<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of the maximum tolerated dose (MTD) by occurrence of dose limiting toxicities (DLT) |  | up to 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with drug-related adverse events | according to common terminology criteria for adverse events (CTCAE) 3.0 | up to 24 days after last drug administration | 
| Number of patients with abnormal laboratory findings |  | up to 24 days after last drug administration | 
| Change in Eastern Cooperative Oncology Group (ECOG) performance score |  | baseline, up to 24 days after last drug administration | 
| Number of patients with clinically significant changes in vital signs |  | up to 24 days after last drug administration | 
| Number of patients with objective tumor response |  | up to 24 days after last drug administration | 
| Cmax (maximum concentration of the analyte in plasma) |  | up to 264 hours after drug administration | 
| tmax (time from dosing to maximum concentration) |  | up to 264 hours after drug administration | 
| AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) |  | up to 264 hours after drug administration | 
| %AUC0-tz (the percentage of the AUC0-∞ that is obtained by extrapolation) |  | up to 264 hours after drug administration | 
| λz (terminal rate constant in plasma) |  | up to 264 hours after drug administration | 
| t1/2 (terminal half-life of the analyte in plasma) |  | up to 264 hours after drug administration | 
| MRT (mean residence time of the analyte in the body after intravenous administration) |  | up to 264 hours after drug administration | 
| CL (total clearance of the analyte in the plasma after intravascular administration) |  | up to 264 hours after drug administration | 
| Vz (apparent volume of distribution during the terminal phase λz following an intravascular dose) |  | up to 264 hours after drug administration | 
| Vss (apparent volume of distribution at steady state following intravascular administration) |  | up to 264 hours after drug administration |