Evaluating ABX-EGF is the Same as "Panitumumab" in Patients With Metastatic Colorectal Cancer

• Grade 3 or Grade 4 Diarrhea (Part 2) [ Time Frame: Until disease progression (median 47 weeks) ] [ Designated as safety issue: Yes ]
  Participant incidence of grade 3 or grade 4 diarrhea in Part 2 of the study
• Grade 3 or Grade 4 Diarrhea (Part 1) [ Time Frame: Until disease progression (median 35 weeks) or 48 weeks, whichever occurred first ] [ Designated as safety issue: Yes ]
  Participant incidence of grade 3 or grade 4 diarrhea in Part 1 of the study

• Objective Tumor Response (Part 2) [ Time Frame: Until disease progression (median 47 weeks) ] [ Designated as safety issue: No ]
  Objective tumor response (complete or partial) in Part 2 of the study, based on Response Evaluation Criteria in Solid Tumors (RECIST), where complete response = disappearance of all target lesions, partial response = ≥30% reduction in lesion size, progressive disease = ≥20% increase in tumor size; otherwise stable disease.
• Time to Disease Progression (Part 2) [ Time Frame: Until disease progression (median 47 weeks) ] [ Designated as safety issue: No ]
  Kaplan-Meier estimate of median time from the first dose of study drug to disease progression or death if due to disease progression (whichever comes first) in Part 2 of the study. The measure of dispersion for the median could not be estimated, so the number of participants with events is presented in lieu of the median.
• Progression-free Survival Time (Part 2) [ Time Frame: Until disease progression (median 47 weeks) ] [ Designated as safety issue: No ]
  Kaplan-Meier estimate of median time from enrollment to death or disease progression in Part 2 of the study. The measure of dispersion could not be calculated for the median, so the number of participants with events is presented in lieu of the median.
• Survival Time (Part 2) [ Time Frame: Until disease progression (median 47 weeks) ] [ Designated as safety issue: No ]
  Kaplan-Meier estimate of the median time from enrollment to death from any cause during first 58 weeks of the study. Median time to death could not be estimated using Kaplan-Meier methodology. The number of participants who died during this time frame is presented in lieu of the median.
• Objective Tumor Response (Part 1) [ Time Frame: Until disease progression (median 35 weeks) or 48 weeks, whichever occurred first ] [ Designated as safety issue: No ]
  Objective tumor response (complete or partial) in Part 1 of the study, based on Response Evaluation Criteria in Solid Tumors (RECIST), where complete response = disappearance of all target lesions, partial response = ≥30% reduction in lesion size, progressive disease = ≥20% increase in tumor size; otherwise stable disease.
• Progression-free Survival Time (Part 1) [ Time Frame: Until disease progression (median 35 weeks) or 48 weeks, whichever occurred first ] [ Designated as safety issue: No ]
  Kaplan-Meier estimate of median time from enrollment to death or disease progression in Part 1 of the study.
• Time to Disease Progression (Part 1) [ Time Frame: Until disease progression (median 35 weeks) or 48 weeks, whichever occurred first ] [ Designated as safety issue: No ]
  Kaplan-Meier estimate of the median time from the first dose of study drug to disease progression or death if due to disease progression (whichever comes first) in Part 1 of the study.
• Survival Time (Part 1) [ Time Frame: Until disease progression (median 35 weeks) or 48 weeks, whichever occurred first ] [ Designated as safety issue: No ]
  Kaplan-Meier estimate of the median time from enrollment to death from any cause during first 58 weeks of the study. Measure of dispersion for the median time to death could not be estimated using Kaplan-Meier methodology. The number of participants who died during this time frame is presented in lieu of the median.
• Time to Treatment Failure (Part 1) [ Time Frame: Until disease progression (median 35 weeks) or 48 weeks, whichever occurred first ] [ Designated as safety issue: No ]
  Kaplan-Meier estimate of the median time from the date of first dose of panitumumab or chemotherapy to the date the decision was made to end treatment for any reason in Part 1 of the study.
• Time to Initial Objective Tumor Response (Part 1) [ Time Frame: Until disease progression (median 35 weeks) or 48 weeks, whichever occurred first ] [ Designated as safety issue: No ]
  Median time to first observed objective tumor response (complete or partial) among responders in Part 1 of the study.

The purpose of this study is to determine if ABX-EGF is the same as "Panitumumab" , in combination with irinotecan, leucovorin, and 5-fluorouracil (5-FU) is safe and efficacious in patients with metastatic colorectal cancer.

• Drug: Irinotecan
  180 mg/m2 once a week for 6 weeks until disease progression or unable to tolerate
• Drug: ABX-EGF is the same as "Panitumumab"
  All subjects will receive IV infusions of ABX-EGF once every 6 weeks.
• Drug: 5-Fluorouracil
  Bolus 400 mg/m2 and Infusional 2400-3000 mg/m2 over 46 hours once a week for 6 weeks until disease progression or unable to tolerate
• Drug: Leucovorin
  400 mg/m2 once a week for 6 weeks until disease progression or unable to tolerate

• Experimental: ABX-EGF is the same as "Panitumumab"
  2.5 mg/kg once a week for 6 weeks until disease progression or unable to tolerate
  Interventions:

  • Drug: Irinotecan
  • Drug: ABX-EGF is the same as "Panitumumab"
  • Drug: 5-Fluorouracil
  • Drug: Leucovorin
• Active Comparator: Comparator

  5-Fluorouracil- Bolus 400 mg/m2 and Infusional 2400-3000 mg/m2 over 46 hours once a week for 6 weeks until disease progression or unable to tolerate.

  Leucovorin - 400 mg/m2 once a week for 6 weeks until disease progression or unable to tolerate.

  Irinotecan - 180 mg/m2 once a week for 6 weeks until disease progression or unable to tolerate.

  Interventions:

  • Drug: Irinotecan
  • Drug: 5-Fluorouracil
  • Drug: Leucovorin

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)
• ECOG score of 0 or 1
• Adequate hematologic, renal, and hepatic function

Exclusion Criteria:

• Female subject (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 subject who is breast-feeding or pregnant
• Any kind of disorder that compromises the ability of the subject 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 subject 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 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
• Subject unwilling or unable to comply with study requirements
• Known allergy to the ingredients of the study drug or to Staphylococcus protein A