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

Primary Purpose

Colon Cancer, Colorectal Cancer, Rectal Cancer

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Placebo
Pegfilgrastim
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Colon Cancer focused on measuring Neulasta®, pegfilgrastim, Advanced, Chemotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Placebo Comparator

    Arm Label

    Pegfilgrastim

    Placebo

    Arm Description

    6 mg pegfilgrastim

    6 mg placebo

    Outcomes

    Primary Outcome Measures

    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
    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

    Secondary Outcome Measures

    Dose Delay or Reduction Due to Neutropenia
    Dose delay or reduction in chemotherapy doses due to neutropenia
    Dose Delay or Reduction for Any Reason
    Dose delay or reduction in chemotherapy dose during the first 4 cycles for any reason
    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.
    Hospitalization Due to a Neutropenia-Related Event
    Hospitalization because of a neutropenia-related event during the first 4 cycles of treatment
    Progression-Free Survival
    Kaplan-Meier estimate of the median time to disease progression or death
    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.
    Survival
    Death from any cause through the end of the follow-up period
    Antibiotic Use Due to Febrile Neutropenia
    Antibiotic use during any of the first 4 cycles of treatment due to febrile neutropenia.

    Full Information

    First Posted
    October 26, 2004
    Last Updated
    September 20, 2018
    Sponsor
    Amgen
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00094809
    Brief Title
    Chemotherapy Administered Every 2 Weeks With or Without Pegfilgrastim in Subjects With Advanced or Metastatic Colon Cancer
    Official Title
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    February 1, 2003 (Actual)
    Primary Completion Date
    May 19, 2006 (Actual)
    Study Completion Date
    January 23, 2008 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Amgen

    4. Oversight

    5. Study Description

    Brief 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Colon Cancer, Colorectal Cancer, Rectal Cancer
    Keywords
    Neulasta®, pegfilgrastim, Advanced, Chemotherapy

    7. Study Design

    Primary Purpose
    Supportive Care
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    252 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Pegfilgrastim
    Arm Type
    Active Comparator
    Arm Description
    6 mg pegfilgrastim
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    6 mg placebo
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Pegfilgrastim
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Grade 3 or 4 Neutropenia
    Description
    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
    Time Frame
    First 4 cycles of treatment (8 weeks)
    Title
    Grade 4 Neutropenia
    Description
    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
    Time Frame
    First 4 cycles of treatment (8 weeks)
    Secondary Outcome Measure Information:
    Title
    Dose Delay or Reduction Due to Neutropenia
    Description
    Dose delay or reduction in chemotherapy doses due to neutropenia
    Time Frame
    First 4 cycles of treatment (8 weeks)
    Title
    Dose Delay or Reduction for Any Reason
    Description
    Dose delay or reduction in chemotherapy dose during the first 4 cycles for any reason
    Time Frame
    First 4 cycles of treatment (8 weeks)
    Title
    Febrile Neutropenia
    Description
    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.
    Time Frame
    First 4 cycles of treatment (8 weeks)
    Title
    Hospitalization Due to a Neutropenia-Related Event
    Description
    Hospitalization because of a neutropenia-related event during the first 4 cycles of treatment
    Time Frame
    First 4 cycles of neutropenia (8 weeks)
    Title
    Progression-Free Survival
    Description
    Kaplan-Meier estimate of the median time to disease progression or death
    Time Frame
    Up to 24 months after first four cycles of treatment
    Title
    Objective Tumor Response
    Description
    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.
    Time Frame
    First 4 cycles of treatment (8 weeks)
    Title
    Survival
    Description
    Death from any cause through the end of the follow-up period
    Time Frame
    Up to 24 months after first four cycles of treatment
    Title
    Antibiotic Use Due to Febrile Neutropenia
    Description
    Antibiotic use during any of the first 4 cycles of treatment due to febrile neutropenia.
    Time Frame
    First 4 cycles of treatment (8 weeks)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    MD
    Organizational Affiliation
    Amgen
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    20378503
    Citation
    Hecht JR, Pillai M, Gollard R, Heim W, Swan F, Patel R, Dreiling L, Mo M, Malik I. A randomized, placebo-controlled phase ii study evaluating the reduction of neutropenia and febrile neutropenia in patients with colorectal cancer receiving pegfilgrastim with every-2-week chemotherapy. Clin Colorectal Cancer. 2010 Apr;9(2):95-101. doi: 10.3816/CCC.2010.n.013.
    Results Reference
    background
    PubMed Identifier
    25851633
    Citation
    Lyman GH, Reiner M, Morrow PK, Crawford J. The effect of filgrastim or pegfilgrastim on survival outcomes of patients with cancer receiving myelosuppressive chemotherapy. Ann Oncol. 2015 Jul;26(7):1452-8. doi: 10.1093/annonc/mdv174. Epub 2015 Apr 7.
    Results Reference
    derived
    Links:
    URL
    http://www.amgentrials.com
    Description
    AmgenTrials clinical trials website
    URL
    http://www.neulasta.com/
    Description
    FDA-approved Drug Labeling

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

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