PACCE: Panitumumab Advanced Colorectal Cancer Evaluation Study
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: Oxaliplatin Based Chemotherapy; Panitumumab; Irinotecan Based Chemotherapy; Bevacizumab
Intervention description: Oxaliplatin-based Chemotherapy Every 2 Week Regimens (Q2W Cycles) consisting of Oxaliplatin, Leucovorin (LV), 5-Fluorouracil (5-FU) - To be determined by physician. On Day 1 irinotecan and LV are given at the same time using different bags and a Y-line followed by 5-FU administration.; PanitumumabPanitumumab is a high affinity (Kd = 5 x 10-11 M) fully human IgG2 monoclonal antibody that is directed against the human EGFr. Panitumumab will be administered by a 30-60 minute IV infusion at a dose of 6 mg/kg once every 2 weeks on the same day of the oxaliplatin- or irinotecan-based chemotherapy and bevacizumab.; Irinotecan-based Chemotherapy Every 2 Week Regimens (Q2W Cycles) - Irinotecan, Leucovorin (LV), 5-Fluorouracil (5-FU) - To be determined by physician. On Day 1 irinotecan and LV are given at the same time using different bags and a Y-line followed by 5-FU administration.; Bevacizumab is a vascular endothelial growth factor (VEGF)-targeted antibody therapy that was administered to subjects intravenously Q2 weeks as per usual standard of care on the same day of chemotherapy and panitumumab administration .
Intervention MeSH terms: Bevacizumab; Panitumumab; Oxaliplatin; Irinotecan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1053.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Panitumumab Advanced Colorectal Cancer Evaluation Study (PACCE Study); Colorectal, Colon, Rectal Cancer, Metastatic Colorectal; Cancer; EGFr, Clinical Trial; Panitumumab, ABX-EGF; Immunex, Abgenix, Amgen; Metastatic Colorectal Cancer; Oncology

Summary:

      The purpose of this study is to assess whether treatment with the study drug, panitumumab
      given concomitantly with every 2 (Q2) week oxaliplatin-based chemotherapy and bevacizumab
      improves progression-free survival (PFS) compared to treatment Q2-week with oxaliplatin-based
      chemotherapy and bevacizumab alone. All subjects will receive Q2-week oxaliplatin- or
      irinotecan-based chemotherapy and bevacizumab. Control arm subjects will not receive
      concomitant panitumumab therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adenocarcinoma of the colon or rectum

          -  Metastatic colorectal cancer (mCRC)

          -  Measurable disease per modified response evaluation criteria in solid tumors (RECIST)
             criteria

          -  ECOG performance status of 0 or 1

          -  Available paraffin-embedded tumor tissue (from primary tumor or metastasis) or
             unstained slides of paraffin-embedded tissue

          -  If history of other primary cancer, subject will be eligible only if she or he has:

               -  Curatively resected non-melanomatous skin cancer;

               -  Curatively treated cervical carcinoma in situ;

               -  Other primary solid tumor curatively treated with no known active disease present
                  and no treatment administered for the last 5 years.

          -  Adequate hematologic data as follows:

               -  Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9 cells/L;

               -  Platelet count greater than or equal to 100 x 10^9/L;

               -  Hemoglobin greater than or equal to 9.0 g/dL. - Adequate renal function:

               -  Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN);

               -  Urinary protein dipstick of less than 2+ (if urinary dipstick 2+ or greater, then
                  excretion of less than or equal to 1000 mg of protein per day as determined by
                  24-hour urine collection).

          -  Adequate hepatic function:

               -  Alkaline phosphatase less than or equal to 3 x ULN (if liver metastases, less
                  than or equal to 5 x ULN);

               -  Aspartate aminotransferase (serum glutamic-oxaloacetic transaminase)(AST) less
                  than or equal to 3 x ULN (if liver metastases, less than or equal to 5 x ULN);

               -  Alanine aminotransferase (serum glutamic-pyruvic transaminase) (ALT) less than or
                  equal to 3 x ULN (if liver metastases, less than or equal to 5 x ULN);

               -  Bilirubin less than or equal to 2 x ULN. - Competent to comprehend, sign, and
                  date an IRB-approved informed consent form

          -  Before any study-specific procedure, the appropriate written informed consent must be
             obtained.

        Exclusion Criteria:

          -  Prior chemotherapy or biologic (i.e., antibody or vaccine) treatment for mCRC disease
             - Last dose of adjuvant or radiosensitizing chemotherapy less than 6 months before
             randomization - Radiotherapy within 14 days before randomization

          -  Elective and/or planned major surgical procedure to be performed during the course of
             this trial (surgery that arises as needed or necessary during the course of the study,
             not agreed a priori, will not make the subject ineligible)

          -  Major surgery within 28 days before randomization

          -  Central nervous system metastases

          -  History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial
             pneumonitis or pulmonary fibrosis on baseline chest X-ray or CT-scan

          -  Clinically significant ascites

          -  Preexisting bleeding diathesis or coagulopathy or the need for full-dose
             anticoagulation

          -  Any of the following within 1 year before randomization:

               -  Myocardial infarction;

               -  Unstable angina;

               -  Symptomatic congestive heart failure;

               -  Serious uncontrolled cardiac arrhythmia;

               -  Cerebrovascular accident or transient ischemic attack;

               -  Gastrointestinal ulcer or hemorrhage;

               -  Hemoptysis;

               -  Pulmonary embolism;

               -  Deep vein thrombosis, or other significant thromboembolic event.

          -  Regular use of non-steroidal anti-inflammatory agents

          -  Female subject of childbearing potential, not abstinent, and not willing to use
             contraceptives during the course of the study and for 6 months following the last dose
             of first-line treatment

          -  Female subject who is breast-feeding or who has positive serum pregnancy test 72 hours
             prior to randomization

          -  Male subject, not abstinent, and not willing to use adequate contraception upon
             enrollment into this study and for 6 months following the last dose of first-line
             treatment

          -  Subject known to be human immunodeficiency virus (HIV) positive

          -  Subject allergic to panitumumab or any components of panitumumab formulation

          -  History of any 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 the conduct of the
             study or interpretation of study results

          -  Subject unwilling or unable to comply with study requirements

          -  Any kind of disorder that compromises the ability of the subject to give written
             informed consent and/or comply with the study procedures