Evaluating Panitumumab (ABX-EGF) in Patients With Metastatic Colorectal Cancer
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: Irinotecan; Panitumumab; 5-Fluorouracil; Leucovorin
Intervention description: Part 1: 125 mg/m^2 IV infusion once a week on weeks 1 through 4 of each 6-week treatment cycle. Part 2: 180 mg/m^2 IV infusion every other week until disease progression or unable to tolerate.; Intravenous (IV) infusions of panitumumab 2.5 mg/kg once a week delivered in 6-week cycles.; Part 1: IV bolus 500 mg/m^2 on weeks 1 through 4 of each 6-week cycle. Part 2: IV bolus 400 mg/m^2 and infusional 2400-3000 mg/m^2 over 46 hours once every other week until disease progression or unable to tolerate.; Part 1: IV bolus 20 mg/m^2 on weeks 1 through 4 of each 6-week cycle. Part 2: 400 mg/m^2 every other week until disease progression or unable to tolerate.
Intervention MeSH terms: Leucovorin; Fluorouracil; Irinotecan; Panitumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Immunex; Panitumumab; ABX-EGF; Abgenix

Summary:

      The purpose of this study is to determine if panitumumab, in combination with irinotecan,
      leucovorin, and 5-fluorouracil (5-FU) is safe and efficacious in patients with metastatic
      colorectal cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Able to comprehend and sign an Institutional Review Board (IRB)-approved informed
             consent form

          -  Pathologic diagnosis of colorectal cancer - Metastatic colorectal adenocarcinoma

          -  If history of adjuvant chemotherapy for colorectal cancer, must have been free of
             disease for greater than or equal to 1 year after completion of adjuvant chemotherapy

          -  Unidimensionally measurable disease

          -  Paraffin-embedded tumor tissue available for immunohistochemistry studies of epidermal
             growth factor receptor (EGFr) expression (archived tissue is acceptable)

          -  Tumor over-expressing EGFr by immunohistochemistry (staining must be the sum of 1+, 2+
             and 3+ in greater than or equal to 10% of evaluated tumor cells; staining and
             evaluation to be conducted at a central laboratory)

          -  Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1

          -  Adequate hematologic, renal, and hepatic function

        Exclusion Criteria:

          -  Female (of childbearing potential, post-menopausal for less than 6 months, not
             surgically sterilized, or not abstinent) not consenting to use adequate contraceptive
             precautions during the course of the study and for 6 months after the last ABX-EGF
             infusion

          -  Female who is breast-feeding or pregnant

          -  Any kind of disorder that compromises the ability of the patient to give written
             informed consent and/or comply with the study procedures

          -  History of any chronic medical or psychiatric condition or laboratory abnormality
             that, in the opinion of the investigator, may increase the risks associated with study
             participation or study drug administration or may interfere with compliance or the
             interpretation of study results

          -  Untreated brain metastases

          -  Therapy for colorectal cancer other than surgery and 5-FU-based adjuvant therapy

          -  Prior treatment for metastatic colorectal cancer

          -  Prior irinotecan

          -  Prior or concurrent radiation therapy for colorectal cancer, including prior adjuvant
             radiation therapy to the pelvis

          -  Known allergy to irinotecan, 5-fluorouracil, or leucovorin

          -  Known Gilbert's disease

          -  Known dihydropyrimidine dehydrogenase (DPD) deficiency

          -  Prior EGFr-targeting agents

          -  Use of investigational therapy used with adjuvant intent within 30 days before the
             first ABX-EGF infusion

          -  If prior history of cancer other than colorectal carcinoma, basal cell carcinoma, or
             cervical carcinoma in situ, no treatment or active disease within 5 years

          -  Active inflammatory bowel disease or other bowel disease (other than colorectal
             carcinoma) causing chronic diarrhea (defined as greater than 4 stools per day)

          -  Partial or complete bowel obstruction, known chronic malabsorption, total colectomy,
             or other major abdominal surgery that might result in substantial alteration in
             transit to absorption of oral medication

          -  Ascites or pleural effusion requiring therapeutic paracentesis or thoracentesis;
             subject with small, stable, asymptomatic pleural effusions or ascites may be enrolled;
             subject who has been rendered asymptomatic by successful sclerosis of an effusion may
             be enrolled.

          -  Active interstitial pneumonia or interstitial fibrosis

          -  Left ventricular ejection fraction (LVEF) less than 45%, as measured by multiple-gated
             acquisition (MUGA) scan - Myocardial infarction within 1 year before the first ABX-EGF
             infusion

          -  Any of the following within 6 months before the first study drug dose:

               -  Unstable angina;

               -  Symptomatic congestive heart failure;

               -  Serious uncontrolled cardiac arrhythmia;

               -  Cerebrovascular accident or transient ischemic attack;

               -  Pulmonary embolism;

               -  Deep vein thrombosis;

               -  Other significant thromboembolic event.

          -  Subject known to be human immunodeficiency virus (HIV) positive

          -  History of any chronic medical or psychiatric condition or laboratory abnormality
             that, in the opinion of the Investigator, may increase the risks associated with study
             participation or study drug administration or may interfere with patient compliance or
             the interpretation of study results

          -  Unwilling or unable to comply with study requirements

          -  Known allergy to the ingredients of the study drug or to Staphylococcus protein A