Clinical trial NCT00710710: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2008-07-04
Enrollment: 89
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Best Objective Response Evaluated According to the RECIST Criteria by Independent Review
timeFrame: Tumour measurements performed at screening (day -21 to -1), at the end of every other treatment period (2x 3 weeks), and at the end of the trial or when a patient concluded the trial, up to 357 days.
Secondary outcomes:
measure: Tumour Control After the Fourth Treatment Course
timeFrame: Tumour measurements performed at screening (day -21 to -1) and at the end of of the fourth 3-week treatment cycle, up to 105 days.
measure: Duration of Overall Response
timeFrame: Tumour measurements performed at screening (day -21 to -1), at the end of every other treatment period (2x 3 weeks), and at the end of the trial or when a patient concluded the trial, up to 357 days.
measure: Progression Free Survival (PFS)
timeFrame: Tumour measurements performed at screening (day -21 to -1), at the end of every other treatment period (2x 3 weeks), and at the end of the trial or when a patient concluded the trial, up to 357 days.
measure: Overall Survival (OS)
timeFrame: From first treatment till the end of the trial or when a patient concluded the trial, up to 336 days.
measure: Best Objective Response Evaluated According to the RECIST Criteria by Investigator Assessment
timeFrame: Tumour measurements performed at screening (day -21 to -1), at the end of every other treatment period (2x 3 weeks), and at the end of the trial or when a patient concluded the trial, up to 357 days.
measure: One-year Survival
timeFrame: 1 year, see description for detailed definition of the time frame.
measure: Number of Participants With Carbohydrate Antigen 19-9 (CA19-9) Response
timeFrame: Blood samples for CA19-9 analysis were collected on Days 1, 2, and 5 of each treatment period, up to 357 days.
measure: Number of Participants With Dose Limiting Toxicity (DLT)
timeFrame: Tumour measurements performed at screening (day -21 to -1), at the end of every other treatment period (2x 3 weeks), and at the end of the trial or when a patient concluded the trial, up to 357 days.
measure: Quality of Life Assessment, Including Clinical Benefit Response: Overall Health
timeFrame: Data from the last available questionnaire for each patient. Questionnaires were taken at screening (day -21 to -1), at the beginning (Day 1) and end (Day 22 ± 3) of every treatment period (3 weeks), and at the end of the trial, up to 357 days.
measure: Quality of Life Assessment, Including Clinical Benefit Response: Quality of Life
timeFrame: Data from the last available questionnaire for each patient. Questionnaires were taken at screening (day -21 to -1), at the beginning (Day 1) and end (Day 22 ± 3) of every treatment period (3 weeks), and at the end of the trial, up to 357 days.
measure: Number of Participants With Incidence and Intensity of Adverse Events Graded According to Common Terminology Criteria for Adverse Events (CTCAE)
timeFrame: From first administration until 21 days after the day of last administration, up to 16 cycles, up to 357 days.
Other outcomes:
Locations:
city: Wien
country: Austria
facility: 1216.10.43001 Boehringer Ingelheim Investigational Site
city: Celle
country: Germany
facility: 1216.10.49013 Boehringer Ingelheim Investigational Site
city: Düsseldorf
country: Germany
facility: 1216.10.49009 Boehringer Ingelheim Investigational Site
city: Essen
country: Germany
facility: 1216.10.49007 Boehringer Ingelheim Investigational Site
city: Freiburg/Breisgau
country: Germany
facility: 1216.10.49001 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1216.10.49005 Boehringer Ingelheim Investigational Site
city: Herne
country: Germany
facility: 1216.10.49010 Boehringer Ingelheim Investigational Site
city: München
country: Germany
facility: 1216.10.49008 Boehringer Ingelheim Investigational Site
city: Stuttgart
country: Germany
facility: 1216.10.49003 Boehringer Ingelheim Investigational Site
city: Ulm
country: Germany
facility: 1216.10.49002 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: