Chemotherapy Administered Every 2 Weeks With or Without Pegfilgrastim in Subjects With Advanced or Metastatic Colon Cancer

Study Overview
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Brief Summary
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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.

Official Title
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Chemotherapy Administered Every 2 Weeks With or Without a Single Injection of Pegfilgrastim as First or Second-Line Treatment in Subjects With Locally Advanced or Metastatic Colon Cancer

Conditions
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Colon Cancer, Colorectal Cancer, Rectal Cancer

Intervention / Treatment
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* Drug: Placebo
* Drug: Pegfilgrastim


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pegfilgrastim<br>6 mg pegfilgrastim | Drug: Pegfilgrastim<br>* 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.<br>|
| Placebo Comparator: Placebo<br>6 mg placebo | Drug: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade 3 or 4 Neutropenia | Grade 3 or 4 neutropenia, defined as an absolute neutrophil count (ANC) < 1 x 10^9/L, in any of the first four cycles of treatment | First 4 cycles of treatment (8 weeks) | 
| Grade 4 Neutropenia | Grade 4 neutropenia, defined as an absolute neutrophil count (ANC) <0.5 x 10^9/L, in any of the first four cycles of treatment | First 4 cycles of treatment (8 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Delay or Reduction Due to Neutropenia | Dose delay or reduction in chemotherapy doses due to neutropenia | First 4 cycles of treatment (8 weeks) | 
| Dose Delay or Reduction for Any Reason | Dose delay or reduction in chemotherapy dose during the first 4 cycles for any reason | First 4 cycles of treatment (8 weeks) | 
| Febrile Neutropenia | Febrile neutropenia, Defined as a temperature ≥ 38.2 °C on a given day, with an ANC < 1.0 x 10^9/L recorded on the same day or the next day, during any of the first 4 cycles of treatment. | First 4 cycles of treatment (8 weeks) | 
| Hospitalization Due to a Neutropenia-Related Event | Hospitalization because of a neutropenia-related event during the first 4 cycles of treatment | First 4 cycles of neutropenia (8 weeks) | 
| Progression-Free Survival | Kaplan-Meier estimate of the median time to disease progression or death | Up to 24 months after first four cycles of treatment | 
| Objective Tumor Response | Objective tumor response (complete or partial) at the end of treatment, defined as a reduction of at least 50% in the area of all measurable lesions (partial response) or disappearance of all measurable or evaluable disease without the development of new lesions (complete response) on computed tomographic (CT) or other scanning. | First 4 cycles of treatment (8 weeks) | 
| Survival | Death from any cause through the end of the follow-up period | Up to 24 months after first four cycles of treatment | 
| Antibiotic Use Due to Febrile Neutropenia | Antibiotic use during any of the first 4 cycles of treatment due to febrile neutropenia. | First 4 cycles of treatment (8 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neulasta®, pegfilgrastim, Advanced, Chemotherapy