Clinical trial NCT00042939: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: pancreatic cancer
metastatic pancreatic cancer
EGF-r
irinotecan
docetaxel
cetuximab
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 94
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: 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)

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

Primary outcomes:
measure: Proportion of Patients With Objective Response Evaluated by RECIST (Solid Tumor Response Criteria)
timeFrame: Assessed every 12 weeks until progression
Secondary outcomes:
measure: Progression-free Survival
timeFrame: Assessed every 3 months for 2 years and then every 6 months for 1 year
measure: Overall Survival
timeFrame: Assessed every 3 months for 2 years and then every 6 months for 1 year
measure: Epidermal Growth Factor Receptor (EGFR) Status
timeFrame: Original tumor tissue samples submitted within one month of patient randomization
measure: Proportion of Patients With Thromboembolic Events
timeFrame: Assessed every 6 weeks while on treatment and for 30 days after the end of treatment
Other outcomes:
Locations:
Study officials:
affiliation: Fox Chase Cancer Center
name: Barbara A. Burtness, MD
role: STUDY_CHAIR
References:
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.
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.