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NCT00911170

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

Last Updated: 2017-12-29

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

847 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-11-03

Study Completion Date

2015-01-02

Brief Summary

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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.

Detailed Description

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Conditions

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Cancer Colon Cancer Colorectal Cancer Fever Locally Advanced Metastatic Colorectal Cancer Neutropenia Rectal Cancer

Keywords

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adenocarcinoma of the colon or rectum febrile neutropenia Bevacizumab Avastin 5-fluorouracil, Oxaliplatin, Leucovorin (FOLFOX) 5-fluorouracil, Irinotecan, Leucovorin (FOLFIRI)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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).

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Bevacizumab

Intervention Type BIOLOGICAL

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

Standard Chemotherapy

Intervention Type DRUG

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.

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).

Group Type PLACEBO_COMPARATOR

Pegfilgrastim

Intervention Type DRUG

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

Bevacizumab

Intervention Type BIOLOGICAL

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

Standard Chemotherapy

Intervention Type DRUG

Interventions

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Pegfilgrastim

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Bevacizumab

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

Intervention Type BIOLOGICAL

Standard Chemotherapy

Intervention Type DRUG

Other Intervention Names

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Neulasta® Avastin®

Eligibility Criteria

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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:

* Absolute neutrophil count at least 1.5 x 10\^9/L
* Platelet count at least 100 x 10\^9/L
* Bilirubin ≤ 1.5 times upper limit of normal
* Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x upper limit of normal or Aspartate aminotransferase and alanine aminotransferase ≤ 5.0 x upper limit of normal if attributable to liver metastasis
* An in-range international normalized ratio (INR) (in-range is usually defined as between 2 and 3) for patients on a stable dose of oral anticoagulant or stable dose of low molecular weight heparin
* Has no active bleeding or pathological condition that carries high risk of bleeding (eg, tumor involving major vessels or known varices). If a suspicion of bleeding diathesis exists, a bleeding time should be performed
* Creatinine ≤ 1.5 times upper limit of normal

General:

* Written informed consent obtained
* Afebrile on day 1 of cycle 1
* Must be able and willing to comply with study and/or follow-up procedures

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

Laboratory:

\- Proteinuria \> 1+, or total quantitative protein \> 500 mg protein/day as determined by 24-hr urine collection

Medications:

* Prior radiotherapy unless treatment was limited to the target lesion and only 1 measurable lesion was treated. Progression of the irradiated lesion must be demonstrated. Patients may not have received prior radiotherapy to greater than 25% of bone marrow. Radiation must have concluded ≥ 4 weeks prior to enrollment. Prior radio-sensitizing chemoradiation will be allowed as long as it was concluded ≥ 4 weeks prior to enrollment.
* Radiotherapy to non-target lesions for pain control will be allowed
* Prior bevacizumab use or other agents targeting VEGF
* Concurrent use of other biological agents
* Use of systemic anti-infectives for active infection, during the 3 calendar days before starting study chemotherapy and bevacizumab or planned during the study treatment period

General:

* Current, recent (within 4 weeks of the first infusion of this study), or planned participation (during the study treatment period) in an experimental therapeutics study other than this protocol
* Female participants who are pregnant or lactating or men and women of reproductive potential not willing to employ an effective method of birth control during treatment and for 20 weeks for women, and 30 weeks for men after discontinuing study treatment
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab, irinotecan, 5-fluorouracil (5-FU), oxaliplatin, or leucovorin, including known sensitivity to E. Coli derived products (eg, Filgrastim, HUMULIN insulin, L-asparaginase)
* Known dihydropyrimidine dehydrogenase deficiency

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Explore related publications, articles, or registry entries linked to this study.

Pinter T, Klippel Z, Cesas A, Croitoru A, Decaestecker J, Gibbs P, Hotko Y, Jassem J, Kurteva G, Novotny J, O'Reilly S, Salek T, Reiner M, Morrow PK, Choi MR, Whittaker S, Blanke C. A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Pegfilgrastim in Patients Receiving First-Line FOLFOX/Bevacizumab or FOLFIRI/Bevacizumab for Locally Advanced or Metastatic Colorectal Cancer: Final Results of the Pegfilgrastim and Anti-VEGF Evaluation Study (PAVES). Clin Colorectal Cancer. 2017 Jun;16(2):103-114.e3. doi: 10.1016/j.clcc.2016.08.008. Epub 2016 Sep 7.

Reference Type BACKGROUND

PMID: 28038865 (View on PubMed)

Other Identifiers

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20080259

Identifier Type: -

Identifier Source: org_study_id

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

Study Results

Basic Information

Brief Summary

Detailed Description

Conditions

Keywords

Study Design

Study Groups

Placebo

Placebo

Bevacizumab

Standard Chemotherapy

Pegfilgrastim

Pegfilgrastim

Bevacizumab

Standard Chemotherapy

Interventions

Pegfilgrastim

Placebo

Bevacizumab

Standard Chemotherapy

Other Intervention Names

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Sponsors

Amgen

Responsible Party

Principal Investigators

MD

Locations

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