Phase I Study of BI 831266 in Patients With Advanced Solid Tumours

• Safety parameters (incidence and intensity of AEs graded according to the common terminology criteria for AEs and incidence of DLT) [ Time Frame: throughout the study period ] [ Designated as safety issue: Yes ]
• Pharmacokinetic parameters [ Time Frame: throughout the study period ] [ Designated as safety issue: No ]
• Pharmacodynamic analysis [ Time Frame: 3-4 weeks ] [ Designated as safety issue: No ]
• Efficacy data (progression free survival, objective response rate, response duration) [ Time Frame: throughout the study period ] [ Designated as safety issue: No ]

The main objective of this trial is to provide safety data in terms of drug-related adverse events for the recommendation of the dose for further trials in the development of BI 831266.

Secondary objectives are the collection of antitumour efficacy data and the determination of the pharmacokinetic and pharmacodynamic profile of BI 831266.

• Drug: Arm A
  Dose escalation Arm A (4 weeks)
• Drug: Arm B
  Dose escalation Arm B (3 weeks)

• Experimental: Arm A
  BI 831266 24h infusion on day 1 and day 15 every 4 weeks
  Intervention: Drug: Arm A
• Experimental: Arm B
  BI 831266 24h infusion on day 1 every 3 weeks
  Intervention: Drug: Arm B

Inclusion criteria:

1. Patients with confirmed diagnosis of advanced, non-resectable and/or metastatic solid malignant tumours, who have failed conventional treatment or for whom no therapy of proven efficacy exists or who are not amenable to established treatment options
2. Secure central venous access
3. Measurable and/or non-measurable tumour deposits
4. Recovery from toxicities of prior anti-cancer therapies at least to CTCAE grade 1
5. Age >= 18 years
6. Life expectancy >= 3 months
7. Written informed consent in accordance with International Conference on Harmonisation guideline for Good Clinical Practice and local legislation
8. Eastern Cooperative Oncology Group performance score <= 2

Exclusion criteria:

1. Serious illness, concomitant non-oncological disease (e.g. active infectious disease), or ongoing toxicity of prior therapies considered by the investigator to potentially compromise patients' safety in this trial
2. Pregnancy or breastfeeding
3. Symptomatic brain metastases and/or leptomeningeal disease requiring therapy
4. Second malignancy requiring therapy
5. Left ventricular ejection fraction (LVEF) < 50% in echocardiography
6. Clinically significant (i.e. active) cardiovascular disease: CVA/stroke (<= 6 months prior to randomisation), myocardial infarction (<= 6 months prior to randomisation), unstable angina, New York Heart Association Grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication
7. Absolute neutrophil count less than 1500 / mm3
8. Platelet count less than 100 000 / mm3
9. Bilirubin greater than 1.5 mg / dl (> 26 micromol / L, SI unit equivalent)
10. 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)
11. Serum creatinine greater than 1.5 mg / dl (> 132 micromol / L, SI unit equivalent)
12. Women and men who are sexually active and unwilling to use a medically acceptable method of contraception
13. Treatment with other investigational drugs or in another clinical trial within the past two weeks before start of therapy or concomitantly with this trial
14. Chemo-, hormone, radio- or immunotherapy within the past two weeks before start of therapy or concomitantly with this trial
15. Patients unable to comply with the protocol
16. Active alcohol or drug abuse