Chemotherapy Administered Every 2 Weeks With or Without Pegfilgrastim in Subjects With Advanced or Metastatic Colon Cancer
Condition: Colon Cancer; Colorectal Cancer; Rectal Cancer
MeSH terms: Colonic Neoplasms
Intervention: Placebo; Pegfilgrastim
Intervention description: Subjects randomized to placebo will receive a 6 mg subcutaneous injection once per cycle at least 24 hours after completion of 5-FU chemotherapy infusion. Subjects will continue to receive one injection per cycle until completion of 4 cycles, or until early termination from the study treatment period, whichever occurs first.; Subjects randomized to pegfilgrastim will receive a 6 mg subcutaneous injection once per cycle at least 24 hours after completion of 5-FU chemotherapy infusion. Subjects will continue to receive one injection per cycle until completion of 4 cycles, or until early termination from the study treatment period, whichever occurs first.
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 252.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Neulasta®; pegfilgrastim; Advanced; Chemotherapy

Summary:

      The purpose of this research study is to evaluate the safety and effectiveness of
      pegfilgrastim in reducing grade 3/4 neutropenia when given after one of three chemotherapy
      regimens (FOIL, FOLFOX or FOLFIRI) in patients with locally advanced or metastatic colorectal
      cancer. This study is considered to be "investigational" because the time between receiving
      pegfilgrastim and the next cycle of chemotherapy is only 11 days.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Locally advanced or metastatic colorectal adenocarcinoma not curable by surgery or
             amenable to radiation therapy with curative intent.

          -  Histologically or cytologically documented locally advanced or metastatic colorectal
             cancer. The site of the primary lesion must be or has been confirmed endoscopically,
             radiologically, or surgically to be or has been in the large bowel.

          -  Measurable or evaluable disease.

          -  ECOG performance status 0, 1 or 2

          -  Life expectancy ≥ 12 weeks

          -  All of the following: (1) ≥ 4 weeks must have elapsed from the time of major surgery
             and subjects must have recovered from the effects (e.g., laparotomy); (2) ≥ 2 weeks
             must have elapsed from the time of minor surgery and subjects must have recovered from
             the operation (insertion of a vascular access device is not considered major or minor
             surgery); (3) ≥ 4 weeks must have elapsed from the time of major radiotherapy (e.g.,
             chest or bone palliative radiation therapy).

          -  Subjects may have received prior adjuvant therapy and one prior chemotherapy regimen
             for metastatic disease providing 30 days has elapsed from last chemotherapy dose.

          -  Subject must have recovered from prior chemotherapy complications and in the opinion
             of the investigator, the subjects current status does not place the subject at risk
             for entry into the trial.

          -  Subjects with prior exposure to both oxaliplatin and irinotecan will not be eligible
             to participate in this study. However, if subject received prior therapy with
             oxaliplatin, they will be eligible to receive the FOLFIRI regimen. If subject received
             prior therapy with irinotecan, they will be eligible to receive the FOLFOX regimen.

          -  Age ≥ 18 years

          -  Absolute neutrophil count ≥ 1.5 x 109/L

          -  Platelet count ≥100 x 109/L

          -  Hemoglobin ≥ 9.0 g/dL (subjects may be receive a red blood cell transfusion to achieve
             this requirement)

          -  Creatinine ≤ 1.5 x UNL

          -  Total bilirubin ≤ 1.5 mg/dL (≤ 25.65 μmol/L), regardless of whether subjects have
             liver involvement secondary to tumor

          -  Aspartate aminotransferase ≤ 5 x UNL

          -  Alkaline phosphatase ≤ 5 x UNL

          -  Informed consent to participate on the study.

        Exclusion Criteria:

          -  Standard chemoradiation as adjuvant treatment for colorectal cancer will be allowed,
             but prior radiotherapy to >15% of bone marrow or outside of standard adjuvant
             colorectal cancer chemoradiation is not allowed.

          -  Known central nervous system metastases or carcinomatous meningitis.

          -  Predisposing colonic or small bowel disorders in which the symptoms are uncontrolled
             as indicated by baseline pattern of >3 loose stools daily in subjects without a
             colostomy or ileostomy. Subjects with a colostomy or ileostomy may be entered at the
             Investigator's discretion.

          -  Pleural effusion or ascites, which cause respiratory compromise (≥Grade 2 dyspnea).

          -  Concurrent use of other investigational agents.

          -  No active infection requiring the start of systemic (intravenous or oral)
             anti-infective (antibiotic, antifungal, antiviral) within 72 hours of the
             administration of the first cycle of study chemotherapy.

          -  Symptomatic sensory peripheral neuropathy.

          -  The following conditions: Uncontrolled high blood pressure; unstable angina;
             symptomatic congestive heart failure; myocardial infarction ≤ 6 months prior to
             randomization; serious uncontrolled cardiac arrhythmia; New York Heart Association
             classification III or IV.

          -  Prior malignancy, except for adequately treated basal cell or squamous cell skin
             cancer, adequately treated noninvasive carcinomas, or other cancer from which the
             patient has been disease-free for at least five years.

          -  Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung.

          -  Medical or psychiatric conditions which, in the opinion of the Investigator, make
             participation in an investigational trial of this nature a poor risk.

          -  Known sensitivity to E. coli derived products (e.g., Filgrastim, HUMULIN® insulin,
             L-asparaginase, HUMATROPE® Growth Hormone, INTRON® A) or known sensitivity to any of
             the products to be administered during dosing.

          -  Subject is currently enrolled or has not yet completed at least 30 days since ending
             other investigational device or drug trial(s) or is receiving other investigational
             agent(s).

          -  Subject of child-bearing potential is evidently pregnant (e.g., positive HCG test) or
             is breast feeding.

          -  Subject is not using adequate contraceptive precautions.

          -  Subject will not be available for follow-up assessment.

          -  Concerns for subject's compliance with the protocol procedures.