Back to resultsIrinotecan and Docetaxel With or Without Cetuximab in Treating Patients With Metastatic Pancreatic Cancer
Primary Purpose
Pancreatic Cancer
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
cetuximab
docetaxel
irinotecan hydrochloride
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Cancer focused on measuring pancreatic cancer, metastatic pancreatic cancer, EGF-r, irinotecan, docetaxel, cetuximab
Eligibility Criteria
Inclusion Criteria: Histologically confirmed metastatic adenocarcinoma of the pancreas Sufficient tumor tissue from fine needle aspiration, core biopsy, or open biopsy available for epidermal growth factor receptor testing At least 1 unidimensionally measurable primary or metastatic lesionge Age of 18 and over ECOG performance status 0-1 Negative pregnancy test Fertile patients must use effective contraception Creatinine clearance > 60 mL/min LVEF normal Absolute neutrophil count > 1,500/mm^3 Platelet count > 100,000/mm^3 Bilirubin ≤ upper limit of normal (ULN)* SGOT or SGPT and alkaline phosphatase must meet the criteria for 1 of the following*: SGOT or SGPT ≤ 2.5 times ULN AND alkaline phosphatase ≤ ULN SGOT or SGPT ≤ 1.5 times ULN AND alkaline phosphatase > ULN but ≤ 2.5 times ULN SGOT or SGPT ≤ ULN AND alkaline phosphatase > 2.5 but ≤ 4 times ULN NOTE: *Percutaneous stenting or endoscopic retrograde cholangiopancreatography may be used to normalize liver function tests Exclusion Criteria: History of uncontrolled arrhythmias History of congestive heart failure History of uncontrolled angina pectoris Prior chemotherapy Pre-existing neuropathy ≥ grade 2 Prior hypersensitivity to polysorbate 80 Pregnant or nursing
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Irinotecan/Docetaxel
Irinotecan/Docetaxel/Cetuximab
Arm Description
Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m². Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. This constituted a cycle of treatment. Patients were evaluated after 2 cycles.
Patients received Cetuximab intravenously once a week for 6 weeks. On day 1 of cycle 1 only, an initial dose of 400 mg/m² (over 120 minutes) was administered. Thereafter, a once-a-week maintenance dose of 250 mg/m² (infused over 60 minutes), was given. The infusion rate never exceeded 5 ml/minute. On the day of the initial dose, the administration of Cetuximab was followed by the administration of docetaxel, after a 60-minute observation period. (The observation period was 30 minutes following maintenance doses.) Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m². Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. Cetuximab was administered once a week for 6 consecutive weeks. A cycle of treatment was 6 weeks.
Outcomes
Primary Outcome Measures
Proportion of Patients With Objective Response Evaluated by RECIST (Solid Tumor Response Criteria)
Per RECIST criteria, Complete response (CR)= disappearance of all target and nontarget lesions Partial response (PR)= >=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits.
Objective response = CR + PR
Secondary Outcome Measures
Progression-free Survival
Progression-free survival was defined as the shorter of:
The time from registration to progression. or
The time from registration to death without documentation of progression given that the death occured within 4 months of the last disease assessment without progression (or registration, whichever is more recent).
Progression is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s) or unequivocal progression of existing nontarget lesions.
Overall Survival
Overall survival was defined as time from registration to death from any cause.
Epidermal Growth Factor Receptor (EGFR) Status
EGFR expression was be evaluated by staining 5-micron paraffin sections of tumor biopsies with anti-EGFR clone 2-18C9 (DAKO Corporation, Carpinteria, CA) using an indirect immunoperoxidase technique according to the instructions provided by DAKO. In brief, this includes an antigen retrieval pretreatment, the blocking of endogenous peroxidase activity, incubation with anti-EGFR antibody or a negative reagent control, staining with a detection system, visualization, and coverslipping.
Proportion of Patients With Thromboembolic Events
To determine the rate of thromboembolic events in this population when prophylactic enoxaparin sodium is administered.
Full Information
NCT ID
NCT00042939
First Posted
August 5, 2002
Last Updated
June 21, 2023
Sponsor
Eastern Cooperative Oncology Group
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00042939
Brief Title
Irinotecan and Docetaxel With or Without Cetuximab in Treating Patients With Metastatic Pancreatic Cancer
Official Title
Phase II Trial of Irinotecan/Docetaxel for Advanced Pancreatic Cancer, With Randomization Between Irinotecan/Docetaxel and Irinotecan/Docetaxel Plus C225 a Monoclonal Antibody to the Epidermal Growth Factor Receptor (EGF-r)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
December 9, 2003 (Actual)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
August 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eastern Cooperative Oncology Group
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining chemotherapy with cetuximab may kill more tumor cells.
PURPOSE: This randomized phase II trial is studying giving irinotecan and docetaxel together with cetuximab to see how well it works compared to irinotecan and docetaxel alone in treating patients with metastatic pancreatic cancer .
Detailed Description
OBJECTIVES:
Determine the efficacy of irinotecan and docetaxel with or without cetuximab, in terms of objective response rate, in patients with metastatic adenocarcinoma of the pancreas.
Determine the time to progression and overall survival of patients treated with these regimens.
Determine the proportion of patients with tumors that overexpress epidermal growth factor receptor.
OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.
Arm A: Patients receive docetaxel IV over 1 hour and irinotecan IV over 30 minutes weekly on days 1, 8, 15, and 22.
Arm B: Patients receive docetaxel and irinotecan as in arm A. Patients also receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36.
Courses repeat in both arms every 6 weeks in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months for 2 years, every 6 months for 1 year, and then periodically thereafter.
PROJECTED ACCRUAL: A total of 92 patients (46 per treatment arm)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer
Keywords
pancreatic cancer, metastatic pancreatic cancer, EGF-r, irinotecan, docetaxel, cetuximab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
94 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Irinotecan/Docetaxel
Arm Type
Active Comparator
Arm Description
Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m².
Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. This constituted a cycle of treatment. Patients were evaluated after 2 cycles.
Arm Title
Irinotecan/Docetaxel/Cetuximab
Arm Type
Experimental
Arm Description
Patients received Cetuximab intravenously once a week for 6 weeks. On day 1 of cycle 1 only, an initial dose of 400 mg/m² (over 120 minutes) was administered. Thereafter, a once-a-week maintenance dose of 250 mg/m² (infused over 60 minutes), was given. The infusion rate never exceeded 5 ml/minute.
On the day of the initial dose, the administration of Cetuximab was followed by the administration of docetaxel, after a 60-minute observation period. (The observation period was 30 minutes following maintenance doses.) Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m².
Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. Cetuximab was administered once a week for 6 consecutive weeks. A cycle of treatment was 6 weeks.
Intervention Type
Biological
Intervention Name(s)
cetuximab
Other Intervention Name(s)
Erbitux, C225
Intervention Description
Patients received cetuximab intravenous infusions, via infusion pump or syringe pump, once a week for 6 weeks.
Intervention Type
Drug
Intervention Name(s)
docetaxel
Other Intervention Name(s)
Taxotere
Intervention Description
Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m² once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. Docetaxel was diluted in 100-150 ml of infusion solution.
Intervention Type
Drug
Intervention Name(s)
irinotecan hydrochloride
Other Intervention Name(s)
Camptosar
Intervention Description
After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m² once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest.
Primary Outcome Measure Information:
Title
Proportion of Patients With Objective Response Evaluated by RECIST (Solid Tumor Response Criteria)
Description
Per RECIST criteria, Complete response (CR)= disappearance of all target and nontarget lesions Partial response (PR)= >=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits.
Objective response = CR + PR
Time Frame
Assessed every 12 weeks until progression
Secondary Outcome Measure Information:
Title
Progression-free Survival
Description
Progression-free survival was defined as the shorter of:
The time from registration to progression. or
The time from registration to death without documentation of progression given that the death occured within 4 months of the last disease assessment without progression (or registration, whichever is more recent).
Progression is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s) or unequivocal progression of existing nontarget lesions.
Time Frame
Assessed every 3 months for 2 years and then every 6 months for 1 year
Title
Overall Survival
Description
Overall survival was defined as time from registration to death from any cause.
Time Frame
Assessed every 3 months for 2 years and then every 6 months for 1 year
Title
Epidermal Growth Factor Receptor (EGFR) Status
Description
EGFR expression was be evaluated by staining 5-micron paraffin sections of tumor biopsies with anti-EGFR clone 2-18C9 (DAKO Corporation, Carpinteria, CA) using an indirect immunoperoxidase technique according to the instructions provided by DAKO. In brief, this includes an antigen retrieval pretreatment, the blocking of endogenous peroxidase activity, incubation with anti-EGFR antibody or a negative reagent control, staining with a detection system, visualization, and coverslipping.
Time Frame
Original tumor tissue samples submitted within one month of patient randomization
Title
Proportion of Patients With Thromboembolic Events
Description
To determine the rate of thromboembolic events in this population when prophylactic enoxaparin sodium is administered.
Time Frame
Assessed every 6 weeks while on treatment and for 30 days after the end of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed metastatic adenocarcinoma of the pancreas
Sufficient tumor tissue from fine needle aspiration, core biopsy, or open biopsy available for epidermal growth factor receptor testing
At least 1 unidimensionally measurable primary or metastatic lesionge
Age of 18 and over
ECOG performance status 0-1
Negative pregnancy test
Fertile patients must use effective contraception
Creatinine clearance > 60 mL/min
LVEF normal
Absolute neutrophil count > 1,500/mm^3
Platelet count > 100,000/mm^3
Bilirubin ≤ upper limit of normal (ULN)*
SGOT or SGPT and alkaline phosphatase must meet the criteria for 1 of the following*:
SGOT or SGPT ≤ 2.5 times ULN AND alkaline phosphatase ≤ ULN
SGOT or SGPT ≤ 1.5 times ULN AND alkaline phosphatase > ULN but ≤ 2.5 times ULN
SGOT or SGPT ≤ ULN AND alkaline phosphatase > 2.5 but ≤ 4 times ULN
NOTE: *Percutaneous stenting or endoscopic retrograde cholangiopancreatography may be used to normalize liver function tests
Exclusion Criteria:
History of uncontrolled arrhythmias
History of congestive heart failure
History of uncontrolled angina pectoris
Prior chemotherapy
Pre-existing neuropathy ≥ grade 2
Prior hypersensitivity to polysorbate 80
Pregnant or nursing
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Barbara A. Burtness, MD
Organizational Affiliation
Fox Chase Cancer Center
Official's Role
Study Chair
12. IPD Sharing Statement
Citations:
Citation
Burtness BA, Powell ME, Berlin JD, et al.: Phase II ECOG trial of irinotecan/docetaxel with or without cetuximab in metastatic pancreatic cancer: updated survival and CA19-9 results. [Abstract] J Clin Oncol 26 (Suppl 15): A-4642, 2008.
Results Reference
result
Citation
Burtness BA, Powell M, Berlin J, et al.: Phase II trial of irinotecan/docetaxel for advanced pancreatic cancer with randomization between irinotecan/docetaxel and irinotecan/docetaxel plus C225, a monoclonal antibody to the epidermal growth factor receptor (EGF-r) : Eastern Cooperative Oncology. [Abstract] J Clin Oncol 25 (Suppl 18): A-4519, 2007.
Results Reference
result
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Irinotecan and Docetaxel With or Without Cetuximab in Treating Patients With Metastatic Pancreatic Cancer
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