CancerPhase 3NCT00911170
PAVES: Pegfilgrastim Anti-vascular Endothelial Growth Factor (VEGF) Evaluation Study
A Phase 3 study testing Pegfilgrastim, Bevacizumab and Standard Chemotherapy in people with Cancer and Colon Cancer, run by Amgen at 154 sites in 17 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer, Colon Cancer, Colorectal Cancer
- What is being tested?
- Pegfilgrastim, Bevacizumab and Standard Chemotherapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 847 participants
- Where
- 154 sitesin 17 countries
- Study dates
- 3 Nov 2009to 2 Jan 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
154 sites in 17 countries.
154 sites in 17 countries
United States72 sites
Research Site
Abingdon, Virginia, 24211
Research Site
Albuquerque, New Mexico, 87131
Research Site
Anaheim, California, 92801
Research Site
Asheville, North Carolina, 28801
Research Site
Bethesda, Maryland, 20817
Research Site
Beverly Hills, California, 90211
Research Site
Billings, Montana, 59101
Research Site
Boston, Massachusetts, 02130
Research Site
Boston, Massachusetts, 02135
Research Site
Bryan, Texas, 77802
Research Site
Canton, Ohio, 44708
Research Site
Cincinnati, Ohio, 45219
Research Site
Corpus Christi, Texas, 78405
Research Site
Corpus Christi, Texas, 78412
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Council Bluffs, Iowa, 51503
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Cumberland, Maryland, 21502
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Dover, Delaware, 19901
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Gainesville, Florida, 32605
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Grand Island, Nebraska, 68803
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Greenwich, Connecticut, 06830
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Gurnee, Illinois, 60031
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Hazard, Kentucky, 41701
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Hickory, North Carolina, 28602
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High Point, North Carolina, 27262
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Hilton Head Island, South Carolina, 29926
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Honolulu, Hawaii, 96813
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Hutchinson, Kansas, 67502
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Jefferson City, Missouri, 65109
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Jonesboro, Arkansas, 72401
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Kansas City, Missouri, 64118
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Kearney, Nebraska, 68845
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Kennewick, Washington, 99336
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Lake Success, New York, 11042
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Lancaster, Pennsylvania, 17605
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Langhorne, Pennsylvania, 19047
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Lexington, Kentucky, 40503
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Little Silver, New Jersey, 07739
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Loxahatchee Groves, Florida, 33470
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Lynchburg, Virginia, 24501
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Massillon, Ohio, 44646
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Maywood, Illinois, 60153
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Middletown, Ohio, 45042
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Modesto, California, 95355
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Muscle Shoals, Alabama, 35661
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Myrtle Beach, South Carolina, 29572
Research Site
Nashville, Tennessee, 37203
Research Site
New Albany, Indiana, 47150
Research Site
Nyack, New York, 10960
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Omaha, Nebraska, 68131
Research Site
Paducah, Kentucky, 42001
Research Site
Port Saint Lucie, Florida, 34952
Research Site
Portsmouth, New Hampshire, 03801
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Quincy, Illinois, 62301
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Randallstown, Maryland, 21133
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Reading, Pennsylvania, 19605
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Rockford, Illinois, 61108
Research Site
San Diego, California, 92161
Research Site
Shreveport, Louisiana, 71103
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Sioux City, Iowa, 51101
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Somerville, New Jersey, 08876
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South Bend, Indiana, 46617
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Spokane, Washington, 99220
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Springfield, Missouri, 65807
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St Louis, Missouri, 63136
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Tamarac, Florida, 33321
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Towson, Maryland, 21204
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Upland, Pennsylvania, 19013
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Waterloo, Iowa, 50701
Research Site
Waterloo, Iowa, 50702
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West Reading, Pennsylvania, 19611
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Willow Grove, Pennsylvania, 19090
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Winston-Salem, North Carolina, 27103
Canada9 sites
Research Site
Brampton, Ontario, L6R 3J7
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Greater Sudbury, Ontario, P3E 5J1
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Laval, Quebec, H7M 3L9
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Lévis, Quebec, G6V 3Z1
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London, Ontario, N6A 4L6
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Montreal, Quebec, H2W 1S6
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Montreal, Quebec, H4J 1C5
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Sault Ste. Marie, Ontario, P6A 5K7
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Toronto, Ontario, M6R 1B5
Hungary9 sites
Research Site
Budapest, 1097
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Budapest, 1125
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Debrecen, 4012
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Győr, 9023
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Gyula, 5700
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Kaposvár, 7400
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Kecskemét, 6000
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Szeged, 6720
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Szolnok, 5004
Ireland7 sites
Research Site
Cork
Research Site
Dublin, 24
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Dublin, 7
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Dublin, 8
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Dublin, 9
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Galway
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Waterford
Russia6 sites
Research Site
Chelyabinsk, 454087
Research Site
Kazan', 420029
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Moscow, 115478
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Saint Petersburg, 197022
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Samara, 443031
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Yaroslavl, 150054
Ukraine6 sites
Research Site
Dnipropetrovsk, 49102
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Donetsk, 83092
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Ivano-Frankivsk, 76018
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Kyiv, 03115
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Lviv, 79031
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Uzhhorod, 88000
Australia5 sites
Research Site
Ballarat, Victoria, 3350
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Coburg, Victoria, 3058
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Footscray, Victoria, 3011
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Frankston, Victoria, 3199
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Hobart, Tasmania, 7000
France5 sites
Research Site
Amiens, 80000
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Bordeaux, 33076
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Cahors, 46005
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Lille, 59037
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Rouen, 76000
Italy5 sites
Research Site
Benevento, 82100
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Palermo, 90100
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Roma (RM), 00133
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Rozzano (MI), 20089
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Taormina (ME), 98039
Poland5 sites
Research Site
Gdansk, 80-952
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Lodz, 93-509
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Olsztyn, 10-228
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Suwałki, 16-400
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Warsaw, 04-125
Bulgaria4 sites
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Sofia, 1606
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Sofia, 1756
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Sofia, 1784
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Varna, 9000
Czechia4 sites
Research Site
Hořovice, 268 31
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Nová Ves pod Pleší, 262 04
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Olomouc, 775 20
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Znojmo, 669 02
Romania4 sites
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Bucharest, 022328
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Bucharest, 022338
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Cluj-Napoca, 400015
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Sibiu, 550245
Slovakia4 sites
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Bratislava, 833 10
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Košice, 041 91
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Rimavská Sobota, 979 01
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Trnava, 917 75
Belgium3 sites
Research Site
Aalst, 9300
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Roeselare, 8800
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Verviers, 4800
Latvia3 sites
Research Site
Daugavpils, 5417
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Riga, 1002
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Riga, 1079
Mexico3 sites
Research Site
Colima, 28030
Research Site
San Luis Potosí City, San Luis P, 78200
Research Site
Toluca, 50080
About this study
Official 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)
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.
- Conditions
- Cancer, Colon Cancer, Colorectal Cancer, Fever, Locally Advanced, Metastatic Colorectal Cancer
- Being tested
- Pegfilgrastim, Placebo, Bevacizumab, Standard Chemotherapy
- Keywords
- adenocarcinoma of the colon or rectum, febrile neutropenia, Bevacizumab, Avastin, 5-fluorouracil, Oxaliplatin, Leucovorin (FOLFOX), 5-fluorouracil, Irinotecan, Leucovorin (FOLFIRI)
- Medical subject headings
- Neoplasms, Colonic Neoplasms, Colorectal Neoplasms, Fever, Neutropenia, Rectal Neoplasms, Febrile Neutropenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PegfilgrastimDrug
Also called Neulasta®
Administered as a single 6 mg subcutaneous injection using a pre-filled syringe. There will be no dosage adjustments for investigational product.
PlaceboDrug
Administered as a single subcutaneous injection using a pre-filled syringe.
BevacizumabBiological
Also called Avastin®
5 mg/kg by intravenous (IV) infusion on day 1 of each 14-day cycle.
Standard ChemotherapyDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 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). Receives: Drug: Placebo; Biological: Bevacizumab; Drug: Standard Chemotherapy |
| Pegfilgrastim | Placebo comparator | 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). Receives: Drug: Pegfilgrastim; Biological: Bevacizumab; Drug: Standard Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Grade 3/4 Febrile Neutropenia Across the First 4 Cycles of Chemotherapy
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.
Measured: Approximately 2 months duration (Daily for 4 cycles of treatment; 2 weeks per cycle)
Secondary outcomes (8)
Overall Survival
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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).
Measured: 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 Febrile Neutropenia Across the First 4 Cycles of Chemotherapy
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.
Measured: 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
Grade 3/4 severe neutropenia is defined as neutropenia with absolute neutrophil count (ANC) <1.0 x 10^9/L.
Measured: Approximately 2 months duration (Daily for 4 cycles of treatment; 2 weeks per cycle)
Percentage of Participants With Grade 4 Neutropenia Across the First 4 Cycles of Chemotherapy
Grade 4 severe neutropenia is defined as neutropenia with absolute neutrophil count (ANC) <0.5 x 10^9/L.
Measured: Approximately 2 months duration (Daily for 4 cycles of treatment; 2 weeks per cycle)
Number of Participants With Adverse Events (AEs)
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.
Measured: Approximately 8 weeks (4 treatment cycles)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2009 (estimated)
- Study start3 Nov 2009
- Primary completion17 Sep 2012
- Study completion2 Jan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 847 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00911170
- Sponsor's protocol ID
- 20080259
- Status last verified
- Dec 2017
- First submitted
- 21 May 2009
- Last updated
- 29 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 28038865
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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)
- ClinicalTrials.gov ID
- NCT00911170
- Acronym / sponsor ID
- 20080259
- Conditions
- Cancer, Colon Cancer, Colorectal Cancer, Fever, Locally Advanced, Metastatic Colorectal Cancer
- Keywords
- adenocarcinoma of the colon or rectum, febrile neutropenia, Bevacizumab, Avastin, 5-fluorouracil, Oxaliplatin, Leucovorin (FOLFOX), 5-fluorouracil, Irinotecan, Leucovorin (FOLFIRI)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 847 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 3 Nov 2009 (actual)
- Primary completion
- 17 Sep 2012 (actual)
- Study completion
- 2 Jan 2015 (actual)
- First posted
- 1 Jun 2009 (estimated)
- Results
- Posted 7 Jan 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo, Biological: Bevacizumab, Drug: Standard ChemotherapyParticipants 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). |
| Pegfilgrastim | Placebo comparator | Drug: Pegfilgrastim, Biological: Bevacizumab, Drug: Standard ChemotherapyParticipants 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PegfilgrastimAlso: Neulasta®Administered as a single 6 mg subcutaneous injection using a pre-filled syringe. There will be no dosage adjustments for investigational product. | Drug | Pegfilgrastim |
| PlaceboAdministered as a single subcutaneous injection using a pre-filled syringe. | Drug | Placebo |
| BevacizumabAlso: Avastin®5 mg/kg by intravenous (IV) infusion on day 1 of each 14-day cycle. | Biological | Pegfilgrastim, Placebo |
| Standard ChemotherapyEach 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. | Drug | Pegfilgrastim, Placebo |
Primary outcome
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.
8 secondary outcomes
Overall Survival
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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 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)
Percentage of Participants With Grade 3/4 Neutropenia Across the First 4 Cycles of Chemotherapy
Time frame: Approximately 2 months duration (Daily for 4 cycles of treatment; 2 weeks per cycle)
Percentage of Participants With Grade 4 Neutropenia Across the First 4 Cycles of Chemotherapy
Time frame: Approximately 2 months duration (Daily for 4 cycles of treatment; 2 weeks per cycle)
Number of Participants With Adverse Events (AEs)
Time frame: Approximately 8 weeks (4 treatment cycles)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 28038865Pinter 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.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
154 sites in 17 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pegfilgrastim, Bevacizumab and Standard Chemotherapy in people with Cancer and Colon Cancer, run by Amgen at 154 sites in 17 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 154 sites in United States, Canada, Hungary, Ireland, Russia and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00911170, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2017.