Open, Randomized Phase II Trial to Investigate the Efficacy and Safety of the PLK-1 Inhibitor BI 2536 in Patients With Advanced, Unresectable Pancreatic Cancer

An Open, Randomised, Clinical Phase II Trial in Patients With Unresectable Advanced Pancreatic Cancer Investigating the Efficacy, Safety, and Pharmacokinetics of BI 2536 Administered in Repeated 3-week Cycles as a Single i.v. Dose of 200 mg on Day 1 or as 60 mg Doses on Days 1, 2, and 3

The trial is conducted in order to evaluate the efficacy, safety and pharmacokinetics of BI 2536 in the treatment of unresectable advanced pancreatic cancer as first line or second line therapy. A secondary aim is to identify the most suitable dosage regimen for the further phase II and III clinical programme of BI 2536. To achieve this objective, two dosage regimens are compared in patients receiving first line therapy.

Inclusion Criteria:

1. male or female patient aged 18 years or older
2. patient with confirmed diagnosis of unresectable, either locally advanced or metastatic, ductal adenocarcinoma of the pancreas
3. patient who is either chemonaïve (for the first line cohorts), or who presents with progressive disease under first line chemotherapy with a gemcitabine based regimen (for the second line cohort)
4. Karnofsky performance status of ¿ 70% for the first line cohorts, and Karnofsky performance status ¿ 50% for the second line cohort
5. patient with at least one measurable tumour lesion that can accurately be measured by magnetic resonance imaging (MRI), or computed tomography (CT) in at least one dimension (longest diameter to be recorded)
6. life expectancy of at least three months
7. patient must have given written informed consent consistent with the guidelines of the international conference on harmonisation for good clinical practice (ICH-GCP) as well as with local legislation

Exclusion Criteria:

1. prior adjuvant chemotherapy (for first line cohorts only)
2. ampullary carcinoma of the pancreas
3. hypersensitivity to the trial drug or the excipients
4. persistence of toxicities of prior anti cancer therapies which are deemed to be clinically relevant
5. known second malignancy requiring therapy
6. brain metastases which are symptomatic or require therapy
7. absolute neutrophil count less than 1.500/mm3
8. platelet count less than 100.000/mm3
9. haemoglobin less than 9 mg/dl
10. aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 2.5 times the upper limit of normal, or AST or ALT greater than 5 times the upper limit of normal in case of known liver metastases
11. bilirubin greater than 3.0 mg/dl (> 52 ¿mol/l, SI unit equivalent) under adequate drainaging measures (in case of obstructive jaundice)
12. serum creatinine greater than 2.0 mg/dl
13. concomitant intercurrent illnesses including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness or social situation that would limit compliance with trial requirement or which are considered relevant for the evaluation of the efficacy or safety of the trial drug
14. radiotherapy within the past four weeks prior to treatment with the trial drug
15. hormone- or immunotherapy or therapy with a biologic response modifier within the past four weeks
16. treatment with any other investigational drug within the past four weeks
17. men or women who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. abstinence, condom with spermicidal coating, diaphragm with spermicidal coating, oral contraceptive, progesterone implant, sterilisation) during the trial
18. pregnancy or lactation
19. patients unable to comply with the protocol