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
  Purpose

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 .


Condition Intervention Phase
Pancreatic Cancer
Biological: cetuximab
Drug: docetaxel
Drug: irinotecan hydrochloride
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • 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



Secondary Outcome Measures:
  • 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.


Enrollment: 94
Study Start Date: July 2003
Study Completion Date: August 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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
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.

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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00042939

Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Barbara A. Burtness, MD Fox Chase Cancer Center
  More Information

Additional Information:
Publications:
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.

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00042939     History of Changes
Other Study ID Numbers: CDR0000069486, U10CA021115, E8200 [ECOG]
Study First Received: August 5, 2002
Results First Received: June 21, 2011
Last Updated: April 2, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Eastern Cooperative Oncology Group:
pancreatic cancer
metastatic pancreatic cancer
EGF-r
irinotecan
docetaxel
cetuximab

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Docetaxel
Cetuximab
Irinotecan
Camptothecin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014