A Phase 3, Randomized, Double-blind, Placebo-controlled Study of Pegfilgrastim Admininstered to Subjects With Newly Diagnosed, Locally-advanced or Metastatic Colorectal Cancer Treated With Bevacizumab & Either 5-fluorouracil, Oxaliplatin, Leucovorin (FOLFOX) or 5-fluorouracil, Irinotecan, Leucovorin (FOLFIRI)
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Cancer
- Sponsor
- Amgen
- Enrollment
- 847
- Locations
- 1
- Primary Endpoint
- Percentage of Participants With Grade 3/4 Febrile Neutropenia Across the First 4 Cycles of Chemotherapy
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This is a phase 3, randomized, double-blind, placebo-controlled multi-center study evaluating the efficacy of pegfilgrastim to reduce the incidence of febrile neutropenia (FN) in patients with newly diagnosed, locally-advanced or metastatic colorectal cancer receiving first-line treatment with bevacizumab and either 5-fluorouracil, Oxaliplatin, Leucovorin (FOLFOX) or 5-fluorouracil, Irinotecan, Leucovorin (FOLFIRI).
This study will also investigate the effect of adding pegfilgrastim to bevacizumab and either FOLFOX or FOLFIRI by evaluating overall survival, progression-free survival, and overall response rate in each arm at regular intervals over a maximum of 60 months follow-up.
Investigators
Eligibility Criteria
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:
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
Arms & Interventions
Placebo
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2, and bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus placebo subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Intervention: Placebo
Placebo
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2, and bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus placebo subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Intervention: Bevacizumab
Placebo
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2, and bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus placebo subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Intervention: Standard Chemotherapy
Pegfilgrastim
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2 and bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus pegfilgrastim 6 mg administered as a single subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Intervention: Pegfilgrastim
Pegfilgrastim
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2 and bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus pegfilgrastim 6 mg administered as a single subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Intervention: Bevacizumab
Pegfilgrastim
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2 and bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus pegfilgrastim 6 mg administered as a single subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Intervention: Standard Chemotherapy
Outcomes
Primary Outcomes
Percentage of Participants With Grade 3/4 Febrile Neutropenia Across the First 4 Cycles of Chemotherapy
Time Frame: Approximately 2 months duration (Daily for 4 cycles of treatment; 2 weeks per cycle)
Grade 3/4 febrile neutropenia (FN) is defined as: • A temperature ≥ 38.0°C (≥ 100.4°F) and absolute neutrophil count (ANC) \< 1.0 × 10\^9/L, where ANC was measured the same day or within ± 1 calendar day of a temperature ≥ 38.0°C (≥ 100.4°F), or • An ANC \< 1.0 × 10\^9/L in combination with: - documented sepsis or infection, OR - neutropenia-related hospitalization where ANC was measured the same day or within ± 1 calendar day. Participants monitored their oral temperatures and maintained diaries to record their temperature twice per day: once in the morning and once in the evening, as well as whenever they suspect they had fever throughout the first 4 cycles of chemotherapy treatment.
Secondary Outcomes
- Overall Survival(From randomization to the data cut-off date of 8 June 2012. Median time on study was 11.6 months and the maximum was 27.6 months.)
- Progression Free Survival(From randomization to the data cut-off date of 8 June 2012. Median time on study was 11.6 months and the maximum was 27.6 months.)
- Time to Progression(From randomization to the data cut-off date of 8 June 2012. Median time on study was 11.6 months and the maximum was 27.6 months.)
- Percentage of Participants With an Objective Response(From randomization to the data cut-off date of 8 June 2012. Median time on study was 11.6 months and the maximum was 27.6 months.)
- Percentage of Participants With Grade 4 Neutropenia Across the First 4 Cycles of Chemotherapy(Approximately 2 months duration (Daily for 4 cycles of treatment; 2 weeks per cycle))
- Number of Participants With Adverse Events (AEs)(Approximately 8 weeks (4 treatment cycles))
- Percentage of Participants With Grade 4 Febrile Neutropenia Across the First 4 Cycles of Chemotherapy(Approximately 2 months duration (Daily for 4 cycles of treatment; 2 weeks per cycle))
- Percentage of Participants With Grade 3/4 Neutropenia Across the First 4 Cycles of Chemotherapy(Approximately 2 months duration (Daily for 4 cycles of treatment; 2 weeks per cycle))