Irinotecan and Docetaxel With or Without Cetuximab in Treating Patients With Metastatic Pancreatic Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT00042939
First received: August 5, 2002
Last updated: April 2, 2013
Last verified: December 2012

August 5, 2002
April 2, 2013
July 2003
June 2009   (final data collection date for primary outcome measure)
Proportion of Patients With Objective Response Evaluated by RECIST (Solid Tumor Response Criteria) [ Time Frame: Assessed every 12 weeks until progression ] [ Designated as safety issue: No ]

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

Not Provided
Complete list of historical versions of study NCT00042939 on ClinicalTrials.gov Archive Site
  • Progression-free Survival [ Time Frame: Assessed every 3 months for 2 years and then every 6 months for 1 year ] [ Designated as safety issue: No ]

    Progression-free survival was defined as the shorter of:

    1. The time from registration to progression. or
    2. 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 [ Time Frame: Assessed every 3 months for 2 years and then every 6 months for 1 year ] [ Designated as safety issue: No ]
    Overall survival was defined as time from registration to death from any cause.
  • Epidermal Growth Factor Receptor (EGFR) Status [ Time Frame: Original tumor tissue samples submitted within one month of patient randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: Assessed every 6 weeks while on treatment and for 30 days after the end of treatment ] [ Designated as safety issue: Yes ]
    To determine the rate of thromboembolic events in this population when prophylactic enoxaparin sodium is administered.
Not Provided
Not Provided
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Irinotecan and Docetaxel With or Without Cetuximab in Treating Patients With Metastatic Pancreatic Cancer
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)

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 .

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)

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Pancreatic Cancer
  • Biological: cetuximab
    Patients received cetuximab intravenous infusions, via infusion pump or syringe pump, once a week for 6 weeks.
    Other Names:
    • Erbitux
    • C225
  • Drug: docetaxel
    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.
    Other Name: Taxotere
  • Drug: irinotecan hydrochloride
    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.
    Other Name: Camptosar
  • Active Comparator: Irinotecan/Docetaxel

    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.

    Interventions:
    • Drug: docetaxel
    • Drug: irinotecan hydrochloride
  • Experimental: Irinotecan/Docetaxel/Cetuximab

    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.

    Interventions:
    • Biological: cetuximab
    • Drug: docetaxel
    • Drug: irinotecan hydrochloride
  • 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.
  • 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
94
August 2009
June 2009   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00042939
CDR0000069486, U10CA021115, E8200 [ECOG]
No
Eastern Cooperative Oncology Group
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Study Chair: Barbara A. Burtness, MD Fox Chase Cancer Center
Eastern Cooperative Oncology Group
December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP