Dose-finding Study of BI 2536 Administered in Combination With Gemcitabine in Patients With Locally Advanced or Metastatic Pancreatic Cancer
Primary Purpose
Pancreatic Neoplasms
Status
Terminated
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
BI 2536, intravenous
Gemcitabine, intravenous
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Neoplasms
Eligibility Criteria
Inclusion Criteria:
Patient with histologically or cytologically confirmed locally advanced, unresectable or metastasized adenocarcinoma of the pancreas who:
- have not received gemcitabine chemotherapy for locally advanced or metastatic pancreatic cancer or
- have progressive disease not before at least 6 months from cessation of adjuvant gemcitabine chemotherapy following curative surgical tumor resection
- Male or female patient aged 18 years or older
- Life expectancy of at least three (3) months
- Eastern Co-operative Oncology Group (ECOG) performance score of 2 or less
- Patient must have given written informed consent
Exclusion Criteria:
- Prior chemo- (other than adjuvant gemcitabine), hormone- (other than Megace®) or immunotherapy
- Ampullary carcinoma of the pancreas
- Brain metastases, which are symptomatic or require therapy
- Patients who have any other life-threatening illness or organ system dysfunction, which in the opinion of the investigator, would either compromise patient safety or interfere with the evaluation of the safety of the test drug
- Other malignancies diagnosed within the past five (5) years (other than non-melanomatous skin cancer)
- Absolute neutrophil count (ANC) <1,500/μl, platelet count <150,000/μl, or hemoglobin <9 g/dl
- Total bilirubin >1.8mg/dl (>30.78 μmol/l,, international system of units (SI) equivalent) under adequate drainage measures (in case of obstructive jaundice)
- No hepatic metastases: Aspartate amino transferase (AST) and/or alanine amino transferase (ALT) >2.5 x upper limit of normal (ULN). Hepatic metastases: aspartate amino transferase (AST) and/or alanine amino transferase (ALT) >5 x ULN
- Serum creatinine >2.0 mg/dl (>176 μmol/L, SI Unit equivalent)
- Radiotherapy within the last 2 weeks prior to or during treatment with the trial drug
- Patients with any serious active infection (i.e., requiring an IV antibiotic, antifungal, or antiviral agents)
- Patients with known HIV, Hepatitis-B or -C infection
- Known or suspected active drug or alcohol abuse
- Women of child-bearing potential; men who are able to father a child and are unwilling to use a medically acceptable method of contraception during the trial
- Pregnancy or breast feeding
- 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
- Patient unable to comply with the protocol
- Patients requiring warfarin (Coumadin®) or patients with a known pre-existing coagulopathy unrelated to pancreatic cancer (This means, for example, that patient with a long (years) history or recurrent venocclusive disease clearly preceding the diagnosis of pancreatic cancer will be excluded from the study. Patients with recent hypercoagulable state (ie deep vein thrombosis or pulmonary embolism) due to pancreatic cancer who are clinically stable on low molecular weight heparin will not be excluded)
- Patients with neuropathy (sensory or motor) ≥ common terminology criteria for adverse events (CTCAE) 3
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
BI 2536 in combination with gemcitabine
Arm Description
Outcomes
Primary Outcome Measures
Occurence of dose limiting toxicity according to CTCAE
Secondary Outcome Measures
Area under the concentration-time curve of the analytes in plasma from time zero to infinity (AUC0-∞)
Maximum measured concentration of the analytes in plasma (Cmax)
Objective tumour responses based on Response evaluation criteria in solid tumors (RECIST) criteria
Survival status
Tumor marker (CA19-9) response to treatment with BI 2536 and gemcitabine
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02215044
Brief Title
Dose-finding Study of BI 2536 Administered in Combination With Gemcitabine in Patients With Locally Advanced or Metastatic Pancreatic Cancer
Official Title
A Phase I Open-label Dose-finding Study of Intravenous BI 2536 Administered in Repeated 4-week Cycles as Repeated Doses on Day 1 and Day 15 in Combination With Gemcitabine Administered on Day 1, Day 8 and Day 15 in Patients With Locally Advanced or Metastatic Pancreatic Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
August 2014
Overall Recruitment Status
Terminated
Study Start Date
June 2007 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
Brief Summary
Determination of the maximum tolerated dose (MTD), safety, and tolerability when BI 2536 was given on Day 1 and Day 15 in combination with gemcitabine given on Day 1, Day 8 and Day 15 every 28 days in patients with locally advanced or metastatic pancreatic adenocarcinoma and characterisation the antitumor activity, pharmacokinetic (PK) profile, and CA 19-9 tumor marker response in response to the combination of BI 2536 with gemcitabine in patients with locally advanced or metastatic pancreatic adenocarcinoma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Neoplasms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BI 2536 in combination with gemcitabine
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
BI 2536, intravenous
Intervention Type
Drug
Intervention Name(s)
Gemcitabine, intravenous
Primary Outcome Measure Information:
Title
Occurence of dose limiting toxicity according to CTCAE
Time Frame
up to day 28 of each cycle
Secondary Outcome Measure Information:
Title
Area under the concentration-time curve of the analytes in plasma from time zero to infinity (AUC0-∞)
Time Frame
Pre-dose, up to 192 hours after start of treatment
Title
Maximum measured concentration of the analytes in plasma (Cmax)
Time Frame
Pre-dose, up to 192 hours after start of treatment
Title
Objective tumour responses based on Response evaluation criteria in solid tumors (RECIST) criteria
Time Frame
up to 1 year
Title
Survival status
Time Frame
up to 1 year
Title
Tumor marker (CA19-9) response to treatment with BI 2536 and gemcitabine
Time Frame
Day 1 of each treatment cycle prior to administration of study treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient with histologically or cytologically confirmed locally advanced, unresectable or metastasized adenocarcinoma of the pancreas who:
have not received gemcitabine chemotherapy for locally advanced or metastatic pancreatic cancer or
have progressive disease not before at least 6 months from cessation of adjuvant gemcitabine chemotherapy following curative surgical tumor resection
Male or female patient aged 18 years or older
Life expectancy of at least three (3) months
Eastern Co-operative Oncology Group (ECOG) performance score of 2 or less
Patient must have given written informed consent
Exclusion Criteria:
Prior chemo- (other than adjuvant gemcitabine), hormone- (other than Megace®) or immunotherapy
Ampullary carcinoma of the pancreas
Brain metastases, which are symptomatic or require therapy
Patients who have any other life-threatening illness or organ system dysfunction, which in the opinion of the investigator, would either compromise patient safety or interfere with the evaluation of the safety of the test drug
Other malignancies diagnosed within the past five (5) years (other than non-melanomatous skin cancer)
Absolute neutrophil count (ANC) <1,500/μl, platelet count <150,000/μl, or hemoglobin <9 g/dl
Total bilirubin >1.8mg/dl (>30.78 μmol/l,, international system of units (SI) equivalent) under adequate drainage measures (in case of obstructive jaundice)
No hepatic metastases: Aspartate amino transferase (AST) and/or alanine amino transferase (ALT) >2.5 x upper limit of normal (ULN). Hepatic metastases: aspartate amino transferase (AST) and/or alanine amino transferase (ALT) >5 x ULN
Serum creatinine >2.0 mg/dl (>176 μmol/L, SI Unit equivalent)
Radiotherapy within the last 2 weeks prior to or during treatment with the trial drug
Patients with any serious active infection (i.e., requiring an IV antibiotic, antifungal, or antiviral agents)
Patients with known HIV, Hepatitis-B or -C infection
Known or suspected active drug or alcohol abuse
Women of child-bearing potential; men who are able to father a child and are unwilling to use a medically acceptable method of contraception during the trial
Pregnancy or breast feeding
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
Patient unable to comply with the protocol
Patients requiring warfarin (Coumadin®) or patients with a known pre-existing coagulopathy unrelated to pancreatic cancer (This means, for example, that patient with a long (years) history or recurrent venocclusive disease clearly preceding the diagnosis of pancreatic cancer will be excluded from the study. Patients with recent hypercoagulable state (ie deep vein thrombosis or pulmonary embolism) due to pancreatic cancer who are clinically stable on low molecular weight heparin will not be excluded)
Patients with neuropathy (sensory or motor) ≥ common terminology criteria for adverse events (CTCAE) 3
12. IPD Sharing Statement
Links:
URL
http://trials.boehringer-ingelheim.com
Description
Related Info
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Dose-finding Study of BI 2536 Administered in Combination With Gemcitabine in Patients With Locally Advanced or Metastatic Pancreatic Cancer
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