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

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Rectal Cancer; Colon Cancer
• Intervention / Treatment: Drug: Pegfilgrastim; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 252
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pegfilgrastim; 6 mg pegfilgrastim	Drug: Pegfilgrastim; 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.
Placebo Comparator: Placebo; 6 mg placebo	Drug: Placebo; 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.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• AmgenTrials clinical trials website
• FDA-approved Drug Labeling

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2003
• Primary Completion (Actual): May 19, 2006
• Study Completion (Actual): January 23, 2008

Study Registration Dates

• First Submitted: October 26, 2004
• First Submitted That Met QC Criteria: October 25, 2004
• First Posted (Estimate): October 26, 2004

Study Record Updates

• Last Update Posted (Actual): October 17, 2018
• Last Update Submitted That Met QC Criteria: September 20, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Advanced; Chemotherapy; pegfilgrastim; Neulasta®
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms
• Other Study ID Numbers: 20020715