PAVES: Pegfilgrastim Anti-vascular Endothelial Growth Factor (VEGF) Evaluation Study

Inclusion Criteria

Disease-related:

• Histologically or cytologically-confirmed adenocarcinoma of the colon or rectum
• Locally-advanced or metastatic disease by radiographic evaluation
• Measurable disease
• Has not previously received chemotherapy for locally-advanced or metastatic colorectal cancer. Patient may have received adjuvant therapy for primary colorectal cancer provided that at least 6 months have elapsed from the time the adjuvant therapy was concluded and recurrent/metastatic disease was documented.
• Eastern Cooperative Oncology Group (ECOG) Performance status 0-2

Demographic:

• Age of 18 years or over

Laboratory:

Adequate organ and marrow function as defined below:

• Absolute neutrophil count at least 1.5 x 10^9/L
• Platelet count at least 100 x 10^9/L
• Bilirubin ≤ 1.5 times upper limit of normal
• Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x upper limit of normal or Aspartate aminotransferase and alanine aminotransferase ≤ 5.0 x upper limit of normal if attributable to liver metastasis
• An in-range international normalized ratio (INR) (in-range is usually defined as between 2 and 3) for patients on a stable dose of oral anticoagulant or stable dose of low molecular weight heparin
• Has no active bleeding or pathological condition that carries high risk of bleeding (eg, tumor involving major vessels or known varices). If a suspicion of bleeding diathesis exists, a bleeding time should be performed
• Creatinine ≤ 1.5 times upper limit of normal

General:

• Written informed consent obtained
• Afebrile on day 1 of cycle 1
• Must be able and willing to comply with study and/or follow-up procedures

Exclusion Criteria

Disease-Related:

• Known brain metastases
• History of another primary malignancy less than/equal to 5 years prior to randomization, with the exception of non-melanoma skin cancer, carcinoma in situ of uterine cervix, and prostatic intraepithelial neoplasia without evidence of prostate cancer
• Prior major surgical procedure less than 28 days prior to day 1 of cycle 1 chemotherapy dosing; anticipated need for major surgical procedure during the 4 cycle treatment period of the study
• Fine needle aspirations or core biopsies within 7 days prior to day 1 of cycle 1 chemotherapy dosing
• Serious nonhealing wound, ulcer, or bone fracture, or history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 1 of cycle 1
• Uncontrolled high blood pressure, history of labile hypertension, uncontrolled congestive heart failure, unstable angina within the past 3 months, myocardial infarction or history of stroke within the past 12 months, unstable symptomatic arrhythmia requiring medication, or clinically significant peripheral vascular disease
• History of clinically significant bleeding within 6 months prior to randomization
• History of arterial or venous thromboembolism within 6 months prior to randomization
• History of other disease including uncontrolled diabetes, serious active or uncontrolled infection, metabolic dysfunction; physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of the prescribed therapy or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications

Laboratory:

• Proteinuria > 1+, or total quantitative protein > 500 mg protein/day as determined by 24-hr urine collection

Medications:

• Prior radiotherapy unless treatment was limited to the target lesion and only 1 measurable lesion was treated. Progression of the irradiated lesion must be demonstrated. Patients may not have received prior radiotherapy to greater than 25% of bone marrow. Radiation must have concluded ≥ 4 weeks prior to enrollment. Prior radio-sensitizing chemoradiation will be allowed as long as it was concluded ≥ 4 weeks prior to enrollment.
• Radiotherapy to non-target lesions