PACCE: Panitumumab Advanced Colorectal Cancer Evaluation Study

PACCE: A Randomized, Open-Label, Controlled, Clinical Trial of Chemotherapy and Bevacizumab With and Without Panitumumab in the First-Line Treatment of Subjects With Metastatic Colorectal Cancer

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.

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