Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00911170




Registration number
NCT00911170
Ethics application status
Date submitted
21/05/2009
Date registered
1/06/2009
Date last updated
29/12/2017

Titles & IDs
Public title
PAVES: Pegfilgrastim Anti-vascular Endothelial Growth Factor (VEGF) Evaluation Study
Scientific title
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)
Secondary ID [1] 0 0
20080259
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 0 0
Colon Cancer 0 0
Colorectal Cancer 0 0
Fever 0 0
Locally Advanced 0 0
Metastatic Colorectal Cancer 0 0
Neutropenia 0 0
Rectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pegfilgrastim
Treatment: Drugs - Placebo
Treatment: Other - Bevacizumab
Treatment: Drugs - Standard Chemotherapy

Placebo comparator: 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).

Placebo comparator: 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).


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

Treatment: Drugs: Placebo
Administered as a single subcutaneous injection using a pre-filled syringe.

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

Treatment: Drugs: Standard Chemotherapy
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.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Grade 3/4 Febrile Neutropenia Across the First 4 Cycles of Chemotherapy
Timepoint [1] 0 0
Approximately 2 months duration (Daily for 4 cycles of treatment; 2 weeks per cycle)
Secondary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
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.
Secondary outcome [2] 0 0
Progression Free Survival
Timepoint [2] 0 0
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.
Secondary outcome [3] 0 0
Time to Progression
Timepoint [3] 0 0
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.
Secondary outcome [4] 0 0
Percentage of Participants With an Objective Response
Timepoint [4] 0 0
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.
Secondary outcome [5] 0 0
Percentage of Participants With Grade 4 Febrile Neutropenia Across the First 4 Cycles of Chemotherapy
Timepoint [5] 0 0
Approximately 2 months duration (Daily for 4 cycles of treatment; 2 weeks per cycle)
Secondary outcome [6] 0 0
Percentage of Participants With Grade 3/4 Neutropenia Across the First 4 Cycles of Chemotherapy
Timepoint [6] 0 0
Approximately 2 months duration (Daily for 4 cycles of treatment; 2 weeks per cycle)
Secondary outcome [7] 0 0
Percentage of Participants With Grade 4 Neutropenia Across the First 4 Cycles of Chemotherapy
Timepoint [7] 0 0
Approximately 2 months duration (Daily for 4 cycles of treatment; 2 weeks per cycle)
Secondary outcome [8] 0 0
Number of Participants With Adverse Events (AEs)
Timepoint [8] 0 0
Approximately 8 weeks (4 treatment cycles)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/11/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/01/2015
Sample size
Target
Accrual to date
Final
847
Recruitment in Australia
Recruitment state(s)
TAS,VIC
Recruitment hospital [1] 0 0
Research Site - Hobart
Recruitment hospital [2] 0 0
Research Site - Ballarat
Recruitment hospital [3] 0 0
Research Site - Coburg
Recruitment hospital [4] 0 0
Research Site - Footscray
Recruitment hospital [5] 0 0
Research Site - Frankston
Recruitment postcode(s) [1] 0 0
7000 - Hobart
Recruitment postcode(s) [2] 0 0
3350 - Ballarat
Recruitment postcode(s) [3] 0 0
3058 - Coburg
Recruitment postcode(s) [4] 0 0
3011 - Footscray
Recruitment postcode(s) [5] 0 0
3199 - Frankston
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Delaware
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Hawaii
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Iowa
Country [11] 0 0
United States of America
State/province [11] 0 0
Kansas
Country [12] 0 0
United States of America
State/province [12] 0 0
Kentucky
Country [13] 0 0
United States of America
State/province [13] 0 0
Louisiana
Country [14] 0 0
United States of America
State/province [14] 0 0
Maryland
Country [15] 0 0
United States of America
State/province [15] 0 0
Massachusetts
Country [16] 0 0
United States of America
State/province [16] 0 0
Missouri
Country [17] 0 0
United States of America
State/province [17] 0 0
Montana
Country [18] 0 0
United States of America
State/province [18] 0 0
Nebraska
Country [19] 0 0
United States of America
State/province [19] 0 0
New Hampshire
Country [20] 0 0
United States of America
State/province [20] 0 0
New Jersey
Country [21] 0 0
United States of America
State/province [21] 0 0
New Mexico
Country [22] 0 0
United States of America
State/province [22] 0 0
New York
Country [23] 0 0
United States of America
State/province [23] 0 0
North Carolina
Country [24] 0 0
United States of America
State/province [24] 0 0
Ohio
Country [25] 0 0
United States of America
State/province [25] 0 0
Pennsylvania
Country [26] 0 0
United States of America
State/province [26] 0 0
South Carolina
Country [27] 0 0
United States of America
State/province [27] 0 0
Tennessee
Country [28] 0 0
United States of America
State/province [28] 0 0
Texas
Country [29] 0 0
United States of America
State/province [29] 0 0
Virginia
Country [30] 0 0
United States of America
State/province [30] 0 0
Washington
Country [31] 0 0
Belgium
State/province [31] 0 0
Aalst
Country [32] 0 0
Belgium
State/province [32] 0 0
Roeselare
Country [33] 0 0
Belgium
State/province [33] 0 0
Verviers
Country [34] 0 0
Bulgaria
State/province [34] 0 0
Sofia
Country [35] 0 0
Bulgaria
State/province [35] 0 0
Varna
Country [36] 0 0
Canada
State/province [36] 0 0
Ontario
Country [37] 0 0
Canada
State/province [37] 0 0
Quebec
Country [38] 0 0
Czechia
State/province [38] 0 0
Horovice
Country [39] 0 0
Czechia
State/province [39] 0 0
Nova Ves pod Plesi
Country [40] 0 0
Czechia
State/province [40] 0 0
Olomouc
Country [41] 0 0
Czechia
State/province [41] 0 0
Znojmo
Country [42] 0 0
France
State/province [42] 0 0
Amiens
Country [43] 0 0
France
State/province [43] 0 0
Bordeaux Cedex
Country [44] 0 0
France
State/province [44] 0 0
Cahors Cedex
Country [45] 0 0
France
State/province [45] 0 0
Lille cedex 01
Country [46] 0 0
France
State/province [46] 0 0
Rouen
Country [47] 0 0
Hungary
State/province [47] 0 0
Budapest
Country [48] 0 0
Hungary
State/province [48] 0 0
Debrecen
Country [49] 0 0
Hungary
State/province [49] 0 0
Gyor
Country [50] 0 0
Hungary
State/province [50] 0 0
Gyula
Country [51] 0 0
Hungary
State/province [51] 0 0
Kaposvar
Country [52] 0 0
Hungary
State/province [52] 0 0
Kecskemet
Country [53] 0 0
Hungary
State/province [53] 0 0
Szeged
Country [54] 0 0
Hungary
State/province [54] 0 0
Szolnok
Country [55] 0 0
Ireland
State/province [55] 0 0
Cork
Country [56] 0 0
Ireland
State/province [56] 0 0
Dublin
Country [57] 0 0
Ireland
State/province [57] 0 0
Galway
Country [58] 0 0
Ireland
State/province [58] 0 0
Waterford
Country [59] 0 0
Italy
State/province [59] 0 0
Benevento
Country [60] 0 0
Italy
State/province [60] 0 0
Palermo
Country [61] 0 0
Italy
State/province [61] 0 0
Roma (RM)
Country [62] 0 0
Italy
State/province [62] 0 0
Rozzano (MI)
Country [63] 0 0
Italy
State/province [63] 0 0
Taormina (ME)
Country [64] 0 0
Latvia
State/province [64] 0 0
Daugavpils
Country [65] 0 0
Latvia
State/province [65] 0 0
Riga
Country [66] 0 0
Mexico
State/province [66] 0 0
San Luis P
Country [67] 0 0
Mexico
State/province [67] 0 0
Colima
Country [68] 0 0
Mexico
State/province [68] 0 0
Toluca
Country [69] 0 0
Poland
State/province [69] 0 0
Gdansk
Country [70] 0 0
Poland
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Lodz
Country [71] 0 0
Poland
State/province [71] 0 0
Olsztyn
Country [72] 0 0
Poland
State/province [72] 0 0
Suwalki
Country [73] 0 0
Poland
State/province [73] 0 0
Warszawa
Country [74] 0 0
Romania
State/province [74] 0 0
Bucharest
Country [75] 0 0
Romania
State/province [75] 0 0
Cluj Napoca
Country [76] 0 0
Romania
State/province [76] 0 0
Sibiu
Country [77] 0 0
Russian Federation
State/province [77] 0 0
Chelyabinsk
Country [78] 0 0
Russian Federation
State/province [78] 0 0
Kazan
Country [79] 0 0
Russian Federation
State/province [79] 0 0
Moscow
Country [80] 0 0
Russian Federation
State/province [80] 0 0
Saint Petersburg
Country [81] 0 0
Russian Federation
State/province [81] 0 0
Samara
Country [82] 0 0
Russian Federation
State/province [82] 0 0
Yaroslavl
Country [83] 0 0
Slovakia
State/province [83] 0 0
Bratislava
Country [84] 0 0
Slovakia
State/province [84] 0 0
Kosice
Country [85] 0 0
Slovakia
State/province [85] 0 0
Rimavska Sobota
Country [86] 0 0
Slovakia
State/province [86] 0 0
Trnava
Country [87] 0 0
Ukraine
State/province [87] 0 0
Dnipropetrovsk
Country [88] 0 0
Ukraine
State/province [88] 0 0
Donetsk
Country [89] 0 0
Ukraine
State/province [89] 0 0
Ivano-Frankivsk
Country [90] 0 0
Ukraine
State/province [90] 0 0
Kyiv
Country [91] 0 0
Ukraine
State/province [91] 0 0
Lviv
Country [92] 0 0
Ukraine
State/province [92] 0 0
Uzhgorod

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT00911170