Intravenous BI 6727 (Volasertib) in 2nd Line Treatment of Urothelial Cancer
Condition: Neoplasms
Intervention: BI 6727, IV infusion
Intervention description: phase II
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of this trial is to evaluate the efficacy and safety of BI 6727 in
      patients with locally advanced, metastatic or recurrent urothelial cancer after failure of
      first line or adjuvant/neoadjuvant chemotherapy.
    

Eligibility 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