Neoplasms

All Conditions

Symptoms and General Pathology

Wounds and Injuries

Blood and Lymph Conditions

Digestive System Diseases

Rare Diseases

Adenocarcinoma

Hyperthermia

Neutropenia

Fever

Febrile Neutropenia

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Agranulocytosis

Leukopenia

Cytopenia

Hematologic Diseases

Leukocyte Disorders

Granulocytopenia

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Herbal and Botanical

Oxaliplatin

Bevacizumab

Leucovorin

Fluorouracil

Irinotecan

Endothelial Growth Factors

Mitogens

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Cola

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).

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).

Administered as a single 6 mg subcutaneous injection using a pre-filled syringe. There will be no dosage adjustments for investigational product.

Pegfilgrastim

Administered as a single subcutaneous injection using a pre-filled syringe.

Placebo

5 mg/kg by intravenous (IV) infusion on day 1 of each 14-day cycle.

Each participant received one of the following chemotherapy regimens at the discretion of treating physician:

FOLFOX: Oxaliplatin, leucovorin, and 5-fluorouracil; FOLFIRI: Irinotecan, leucovorin and 5-flurouracil.

Standard Chemotherapy

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.

PAVES: Pegfilgrastim Anti-vascular Endothelial Growth Factor (VEGF) Evaluation Study

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)

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.

Median time from randomization to date of death caclulated using the Kaplan-Meier method. Participants were censored on the date of last contact (i.e., the date the participant was last known to be alive) if they were not known to have died.

Time from randomization to date of radiological disease progression or death from any cause, whichever event occurs first, calculated using the Kaplan-Meier method. Participants without either event by the analysis data cutoff date were censored on the date of their last evaluable disease assessment. Disease progression based on the investigator's assessment of radiographic scans using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Clinical progression without radiological assessment was not be considered a disease progression in this analysis. Progression defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Time from randomization to date of radiological disease progression calculated using the Kaplan-Meier method. Participants without progression were censored on the date of their last radiographic tumor assessment. Disease progression based on the investigator's assessment of scans using the RECIST v1.1. Clinical progression without radiological assessment was not considered a disease progression. Progression defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

The percentage of participants with a complete response (CR) or partial response (PR) defined by the RECIST v1.1 criteria at any time during the study. Response was be determined by the investigator's assessment of radiographic scans. CR: Disappearance of all non-nodal target lesions and the disappearance of all non-nodal non-target lesions, and no new lesions. All nodal lesions must have reduction of short axis to \< 10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters and no new lesions and/or unequivocal progression of existing non-target lesions, or, the disappearance of all non-nodal target lesions with persistence of one or more non-target lesion(s).

Grade 4 febrile neutropenia (FN) is defined as:

* A temperature ≥ 38.0ºC (≥ 100.4ºF) and absolute neutrophil count (ANC) \< 0.5 × 10\^9/L, where ANC is measured the same day or within +/- 1 calendar day of a temperature ≥ 38.0ºC (≥ 100.4ºF), or
* An ANC \<0.5 × 10\^9/L in combination with:

  * Documented sepsis or infection, OR
  * Neutropenia-related hospitalization where ANC is measured the same day or within +/- 1 calendar day.

Grade 3/4 severe neutropenia is defined as neutropenia with absolute neutrophil count (ANC) \<1.0 x 10\^9/L.

Grade 4 severe neutropenia is defined as neutropenia with absolute neutrophil count (ANC) \<0.5 x 10\^9/L.

A serious adverse event (SAE) is defined as an adverse event that - is fatal; - is life threatening (places the participant at immediate risk of death); - requires inpatient hospitalization or prolongation of existing hospitalization; - results in persistent or significant disability/incapacity; - is a congenital anomaly/birth defect; - other significant medical hazard. AEs were assessed for severity according to National Cancer Institute, Common Terminology Criteria for Adverse Events, Version 3.0, based on this general guideline: Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE; Grade 5 = Death related to AE.

Amgen

All participants in the Primary Analysis Set who received at least 1 dose of investigational product were included in the safety analysis set. One participant was randomized to the placebo arm but actually received pegfilgrastim and is included in the pegfilgrastim arm for the safety analyses.

Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2, plus 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).

Total

Age, Continuous

Sex: Female, Male

American Indian or Alaska Native

Asian

Black or African American

Hispanic or Latino

Japanese

Native Hawaiian or Other Pacific Islander

White

Race/Ethnicity, Customized

FOLFOX

FOLFIRI

Chemotherapy Regimen

North America

Rest of World

North America (Canada and the US) and the Rest of World (Australia, Belgium, Bulgaria, Czech Republic, France, Hungary, Ireland, Italy, Latvia, Mexico, Poland, Romania, Russian Federation, Slovakia, and Ukraine)

Region

Locally Advanced

Metastatic

Disease Status

Colon

Rectum

Primary Tumor Diagnosis

Study Director

The primary hypothesis was that the percentage of participants treated with study chemotherapy and bevacizumab who experience grade 3/4 febrile neutropenia (FN) would be lower in participants randomized to the pegfilgrastim arm compared to placebo arm. The study was designed to have at least 90% power at the 2-sided 0.05 significance level to detect a 6% difference in incidence of grade 3/4 FN from 9% to 3%, which is approximately a 66.7% relative reduction.

The primary analysis set which included all participants with a signed informed consent, and who were randomized and received at least 1 dose of protocol-specified study treatment (chemotherapy, bevacizumab, or investigational product).

Percentage of Participants With Grade 3/4 Febrile Neutropenia Across the First 4 Cycles of Chemotherapy

Overall Survival

Progression Free Survival

Time to Progression

Primary analysis set participants with measurable disease at Baseline.

Percentage of Participants With an Objective Response

Percentage of Participants With Grade 4 Febrile Neutropenia Across the First 4 Cycles of Chemotherapy

Percentage of Participants With Grade 3/4 Neutropenia Across the First 4 Cycles of Chemotherapy

Percentage of Participants With Grade 4 Neutropenia Across the First 4 Cycles of Chemotherapy

Any adverse event

Worst Grade of > 2

Worst Grade of > 3

Worst Grade of > 4

Serious adverse events

Severe adverse events

Life-threatening adverse events

Fatal adverse events

Leading to discontinuation of IP

Leading to discontinuation from study treatment

Safety analysis set, defined as all participants in the Primary Analysis Set who received at least one dose of investigational product (IP; placebo or pegfilgrastim). One participant was randomized to the placebo arm but actually received pegfilgrastim and is included in the pegfilgrastim arm for the safety analyses.

Number of Participants With Adverse Events (AEs)

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). During the long-term follow-up period, further chemotherapy and/or biologic agents (for example, bevacizumab) were to continue at the discretion of the treating physician.

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). During the long-term follow-up period, further chemotherapy and/or biologic agents (for example, bevacizumab) were to continue at the discretion of the treating physician.

Spots Global Cancer Trial Database for adenocarcinoma of the colon or rectum