Open Label Single Arm Phase II Trial of Intravenous BI 6727 in 2nd Line Treatment of Urothelial Cancer

Inclusion Criteria

Inclusion criteria:

1. Histologically or cytologically confirmed urothelial cancer of the bladder, ureters
or renal pelvis.

2. Patients with stage III, IV or recurrent urothelial cancer of the bladder, ureter or
renal pelvis after failure or recurrence after first line or adjuvant/neoadjuvant
chemotherapy. Recurrence is defined as relapse within 2 years after cessation of
prior first-line chemotherapy.

3. Male or female patient aged 18 years or older

4. Life expectancy of at least three (3) months

5. Eastern Co-operative Oncology Group performance score of 2 or less

6. At least one target tumor lesion that has not been irradiated within the past three
months and that can accurately be measured by magnetic resonance imaging (MRI) or
computed tomography (CT) in at least one dimension (longest diameter to be recorded)
as >20 mm with conventional techniques or as >10 mm with spiral CT

7. The patient must have given written informed consent prior to inclusion into the
trial which must be consistent with the International Conference on Harmonization,
Good Clinical Practice (ICH-GCP) and local legislation

Exclusion criteria:

1. More than one prior regimen of chemotherapy including prior adjuvant therapy

2. Brain metastases

3. Patients with bone metastasis as the only site of disease are excluded

4. Serious illness or organ system dysfunction, which in the opinion of the
investigator, would either compromise patient safety, interfere with the evaluation
of the safety of the test drug or limit compliance with trial requirements.

5. QTc prolongation deemed clinically relevant by the investigator

6. Second malignancy currently requiring active therapy

7. Other active malignancy diagnosed within the past 3 years (other than non
melanomatous skin cancer and cervical intraepithelial neoplasia)

8. Absolute neutrophil count (ANC) <1,500/µl

9. Platelet count <100,000/µl

10. Hemoglobin <9 g/dl

11. Total bilirubin >1.5 mg/dl

12. Aspartate amino transferase (AST) and/or alanine amino transferase (ALT) >2.5 x ULN,
or aspartate amino transferase (AST) and/or alanine amino transferase (ALT) >5 x ULN
in case of known liver metastases

13. Serum creatinine >1.5 x ULN

14. Chemo-, Radio- or immunotherapy within the past 4 weeks. This does not apply to
steroids and bisphosphonates.

15. Active infectious disease, or HIV, Hepatitis-B or -C infection

16. Active drug or alcohol abuse

17. Women and men who are sexually active and unwilling to use a medically acceptable
method of contraception (e.g. such as implants, injectables, combined oral
contraceptives, some intrauterine devices or vasectomized partner for participating
females, condoms for participating males) during the trial

18. Pregnancy or breast feeding

19. Treatment with any investigational drug within the past 4 weeks or within less than
four half-life times of the investigational drug before treatment with the trial drug
and/or persistence of toxicities of prior anticancer therapies which are deemed to be
clinically relevant.

20. Prior treatment with Polo-like kinase 1 (Plk1) inhibitor

21. Patient unable to comply with the protocol

22. Any known hypersensitivity to the trial drugs or their excipients