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A Randomized Phase II Study to Determine the Effect of 2 Different Doses AVE0005 (VEGF Trap) in Patients With Metastatic Renal Cell Carcinoma


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Clear Cell Renal Cell Carcinoma, Recurrent Renal Cell Cancer, Stage III Renal Cell Cancer, Stage IV Renal Cell Cancer

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Trial Information

A Randomized Phase II Study to Determine the Effect of 2 Different Doses AVE0005 (VEGF Trap) in Patients With Metastatic Renal Cell Carcinoma


PRIMARY OBJECTIVES:

I. Compare the effect of two different doses of AVE0005 (vascular endothelial growth factor
[VEGF] Trap) treatment on the progression-free proportion at 8 weeks in patients with
metastatic renal cell carcinoma who had previous treatment with a tyrosine kinase inhibitor
(TKI).

SECONDARY OBJECTIVES:

I. Determine the effect of AVE0005 (VEGF Trap) treatment on objective response rate in
patients with metastatic renal cell carcinoma who have had previous TKI treatment.

II. Describe progression-free survival among patients who undergo dose escalation after
progression on low-dose AVE0005 (VEGF Trap).

III. Evaluate the safety and tolerability of AVE0005 (VEGF Trap) in patients with
metastatic renal cell carcinoma who have had previous treatment with a TKI.

IV. Determine the circulating levels of VEGF AVE0005 (VEGF-Trap) complex and correlate it
with clinical activity.

V. Evaluate the modulation of specific angiogenesis-related protein expression by AVE0005
(VEGF Trap).

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior
cytokine therapy (yes vs no) and Memorial Sloan Kettering Cancer Center (MSKCC) risk (low vs
medium vs high). Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive a higher dose of VEGF Trap intervenously (IV) over 1 hour on day 1.

ARM B: Patients receive a lower dose of VEGF Trap IV over 1 hour on day 1.

In both arms, courses repeat every 14 days in the absence of disease progression or
unacceptable toxicity. Patients receiving treatment on arm I may crossover and receive
treatment on arm II if disease progression is evident after 4 courses of treatment.

After completion of study treatment, patients are followed every 3 months for 3 years.


Inclusion Criteria:



- Patient must have histologically confirmed metastatic or unresectable renal cell
carcinoma; disease must be conventional clear cell carcinoma or have a component of
clear cell carcinoma

- Patients with true papillary, sarcomatoid features without any clear cell component,
chromophobe, oncocytoma, collecting duct tumors and transitional cell carcinoma are
NOT eligible

- Patient must have measurable lesions according to the Response Evaluation Criteria In
Solid Tumors (RECIST) criteria; baseline measurements must be performed =< 4 weeks
prior to randomization; all sites of disease, both measurable and nonmeasurable, must
be evaluated =< 4 weeks prior to randomization

- Patient must have evidence of progressive disease following treatment with a tyrosine
kinase inhibitor (TKI) as assessed by the site investigator on the basis of computed
tomography (CT) scans and other appropriate clinical documentation

- Patient must have received at least one prior treatment with a VEGF receptor tyrosine
kinase inhibitor for at least 12 weeks; prior treatment with either temsirolimus or
everolimus is allowed; prior immunotherapy is limited to cytokine therapy with
interleukin 2 and interferon alpha only; no other prior immunotherapy is allowed; no
prior treatment with bevacizumab is allowed

- No prior cellular therapy, vaccine, hormonal or chemotherapy for renal cell carcinoma
is allowed; prior therapy for other cancers is allowable if therapy ended at least 5
years prior to enrollment

- Previous radiotherapy (RT) is permissible provided the measurable disease is outside
the RT port; RT must be completed >= 3 weeks prior to randomization

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Patient must have recovered from any toxic effects of prior radiotherapy or surgical
procedures within 4 weeks prior to randomization

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
serum glutamic pyruvate transaminase (SGPT)(alanine aminotransferase [ALT] =< 3 times
upper limit of normal (ULN)

- Total serum bilirubin =< 1.5 times ULN

- Absolute neutrophil count (ANC) >= 1 x 10^9/L

- Platelet count >= 100 x 10^9/L

- Hemoglobin >= 8.0 g/dL

- Serum calcium =< 12.0 mg/dL

- Calculated creatinine clearance (CrCl) >= 60 mL/min, and either proteinuria =< 500
mg/24 hours or urine protein: creatinine ratio (UPCR) =< 1

- International normalized ratio (INR) within normal limits (or =< 1.5 x ULN if on
prophylactic anticoagulation) and activated partial thromboplastin time (aPTT) within
normal limits

- Patients must not have history of metastatic central nervous system (CNS) disease

- Female patients MUST NOT be pregnant or breastfeeding; due to the unknown teratogenic
properties of AVE0005 (AVE0005 (VEGF Trap), its use in pregnant or breastfeeding
patients is INADVISABLE; for women of childbearing potential, a negative serum
pregnancy test is required within 1 week prior to randomization

- Women of childbearing potential and sexually active males must agree to use an
accepted and effective method of contraception while on this study, and for 6 months
after the completion of the study; if a woman becomes pregnant while she is on this
study or within 6 months after the last dose of protocol therapy, she must inform her
treating physician immediately; if a man impregnates a woman while he is on this
study or within 6 months after the last dose of protocol therapy, he must inform his
treating physician immediately

- Patients who have had basal cell skin cancer, squamous cell skin cancer, in situ
cervical cancer, ductal carcinoma in situ of the breast, or lobular carcinoma in situ
of the breast within the past five years are eligible only if treated with curative
intent

- Patients with other malignancies are eligible only if they have been
continuously disease-free for > 5 years prior to the time of randomization

- Patient must not have any of the following conditions within 24 weeks prior to
randomization:

- Myocardial infarction, severe/unstable angina pectoris, coronary/peripheral
artery bypass graft, New York Heart Association (NYHA) class III or IV
congestive heart failure, cerebrovascular accident or transient ischemic attack

- No prior pulmonary embolism, deep vein thrombosis, or other thromboembolic event

- Patient must not have a history of uncontrolled or labile hypertension, with or
without antihypertensive drug treatment, within 12 weeks prior to drug
administration; this is defined as blood pressure > 150/100 mm Hg or systolic blood
pressure > 180 mm Hg on at least 2 repeated determinations on separate days

- Patient must not have known active infection, evidence of bleeding or intratumoral
bleeding, or underlying bleeding disorder

- Patient must not have a known history of hypersensitivity to any Trap agents or
recombinant proteins

- Human immunodeficiency virus (HIV)-positive patients receiving combination
anti-retroviral therapy are excluded from this study because of possible
pharmacokinetic interactions with AVE0005 (VEGF Trap)

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival rate as assessed by Response Evaluation Criteria in Solid Tumors (RECIST)

Outcome Description:

A two-stage design will be used within each arm.

Outcome Time Frame:

Time from randomization to the earlier of documentation of progression or death, assessed at 8 weeks

Safety Issue:

No

Principal Investigator

Roberto Pili

Investigator Role:

Principal Investigator

Investigator Affiliation:

Eastern Cooperative Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00559

NCT ID:

NCT00357760

Start Date:

December 2007

Completion Date:

Related Keywords:

  • Clear Cell Renal Cell Carcinoma
  • Recurrent Renal Cell Cancer
  • Stage III Renal Cell Cancer
  • Stage IV Renal Cell Cancer
  • Carcinoma
  • Carcinoma, Renal Cell

Name

Location

Johns Hopkins UniversityBaltimore, Maryland  21205
Fox Chase Cancer CenterPhiladelphia, Pennsylvania  19111
Hurley Medical CenterFlint, Michigan  48503
Boulder Community HospitalBoulder, Colorado  80301-9019
Porter Adventist HospitalDenver, Colorado  80210
Rose Medical CenterDenver, Colorado  80220
Swedish Medical CenterEnglewood, Colorado  80110
Sky Ridge Medical CenterLone Tree, Colorado  80124
North Suburban Medical CenterThornton, Colorado  80229
Genesys Hurley Cancer InstituteFlint, Michigan  48503
Bronson Methodist HospitalKalamazoo, Michigan  49007
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Borgess Medical CenterKalamazooaa, Michigan  49001
Fairview Ridges HospitalBurnsville, Minnesota  55337
Hutchinson Area Health CareHutchinson, Minnesota  55350
United HospitalSt. Paul, Minnesota  55102
Ridgeview Medical CenterWaconia, Minnesota  55387
Geisinger Medical CenterDanville, Pennsylvania  17822-0001
Avera Cancer InstituteSioux Falls, South Dakota  57105
Methodist Medical Center of IllinoisPeoria, Illinois  61636
Beth Israel Medical CenterNew York, New York  10003
Via Christi Regional Medical CenterWichita, Kansas  67214
Scott and White Memorial HospitalTemple, Texas  76508
Iowa Methodist Medical CenterDes Moines, Iowa  50309
Iowa Lutheran HospitalDes Moines, Iowa  50316-2301
University of Wisconsin Hospital and ClinicsMadison, Wisconsin  53792-0001
MetroHealth Medical CenterCleveland, Ohio  44109
Sibley Memorial HospitalWashington, District of Columbia  20016
North Colorado Medical CenterGreeley, Colorado  80631
McKee Medical CenterLoveland, Colorado  80539
Cancer Center of Kansas - ChanuteChanute, Kansas  66720
Cancer Center of Kansas - Dodge CityDodge City, Kansas  67801
Cancer Center of Kansas - NewtonNewton, Kansas  67114
Cancer Center of Kansas - SalinaSalina, Kansas  67042
Cancer Center of Kansas - WellingtonWellington, Kansas  67152
Associates in Womens HealthWichita, Kansas  67203
Cancer Center of Kansas - WinfieldWinfield, Kansas  67156
Adena Regional Medical CenterChillicothe, Ohio  54601
Grady Memorial HospitalDelaware, Ohio  43015
Fairfield Medical CenterLancaster, Ohio  43130
Avera McKennan Hospital and University Health CenterSioux Falls, South Dakota  57105
Paoli Memorial HospitalPaoli, Pennsylvania  19301-1792
Memorial HospitalCarthage, Illinois  62321
Galesburg Cottage HospitalGalesburg, Illinois  61401
Galesburg ClinicGalesburg, Illinois  61401
Mason District HospitalHavana, Illinois  62644
McDonough District HospitalMacomb, Illinois  61455
BroMenn Regional Medical CenterNormal, Illinois  61761
Proctor HospitalPeoria, Illinois  61614
Perry Memorial HospitalPrinceton, Illinois  61356
Creighton University Medical CenterOmaha, Nebraska  68131-2197
Bryn Mawr HospitalBryn Mawr, Pennsylvania  19010
Exempla Lutheran Medical CenterWheat Ridge, Colorado  80033
Eureka HospitalEureka, Illinois  61530
Mercy HospitalCoon Rapids, Minnesota  55433
Graham Hospital AssociationCanton, Illinois  61520
Saint Joseph Medical CenterJoliet, Illinois  60435
Pekin HospitalPekin, Illinois  61554
Medical Oncology and Hematology AssociatesDes Moines, Iowa  50309
Ottumwa Regional Health CenterOttumwa, Iowa  52501
Saint Joseph Mercy HospitalAnn Arbor, Michigan  48106
Fairview-Southdale HospitalEdina, Minnesota  55435
Abbott-Northwestern HospitalMinneapolis, Minnesota  55407
Regions HospitalSaint Paul, Minnesota  55101
Saint Francis Regional Medical CenterShakopee, Minnesota  55379
Rice Memorial HospitalWillmar, Minnesota  56201
Mary Imogene Bassett HospitalCooperstown, New York  13326
Geisinger Medical GroupState College, Pennsylvania  16801
Swedish American HospitalRockford, Illinois  61104
Eastern Connecticut Hematology and Oncology AssociatesNorwich, Connecticut  06360
Cancer Center of Kansas - Fort ScottFort Scott, Kansas  66701
Cancer Center of Kansas-IndependenceIndependence, Kansas  67301
Lawrence Memorial HospitalLawrence, Kansas  66044
Mary Rutan HospitalBellefontaine, Ohio  43311
Knox Community HospitalMount Vernon, Ohio  43050
UW Cancer Center Johnson CreekJohnson Creek, Wisconsin  53038
Longmont United HospitalLongmont, Colorado  80501
Manchester Memorial HospitalManchester, Connecticut  06040-4188
University of PittsburghPittsburgh, Pennsylvania  15261
Hennepin County Medical CenterMinneapolis, Minnesota  
University of FloridaGainesville, Florida  32610-0277
Saint Alphonsus Regional Medical CenterBoise, Idaho  83706
Emory UniversityAtlanta, Georgia  30322
Riverside Methodist HospitalColumbus, Ohio  43214
Licking Memorial HospitalNewark, Ohio  43055-2899
Cancer Center of Kansas - McPhersonMcPherson, Kansas  67460
Columbus CCOPColumbus, Ohio  43206
Indiana University Medical CenterIndianapolis, Indiana  46202
Presbyterian - Saint Lukes Medical Center - Health OneDenver, Colorado  80218
Wichita CCOPWichita, Kansas  67214-3882
Alegent Health Immanuel Medical CenterOmaha, Nebraska  68122
Alegent Health Bergan Mercy Medical CenterOmaha, Nebraska  68124
Metro-Minnesota CCOPSt. Louis Park, Minnesota  
Lakeview HospitalStillwater, Minnesota  55082
Lankenau HospitalWynnewood, Pennsylvania  19096
Littleton Adventist HospitalLittleton, Colorado  80122
Parker Adventist HospitalParker, Colorado  80138
New Ulm Medical CenterNew Ulm, Minnesota  56073
OSF Saint Francis Medical CenterPeoria, Illinois  61637
The Medical Center of AuroraAurora, Colorado  80012
Penrose-Saint Francis HealthcareColorado Springs, Colorado  80907
Saint Anthony Central HospitalDenver, Colorado  80204
Exempla Saint Joseph HospitalDenver, Colorado  80218
Colorado Cancer Research Program CCOPDenver, Colorado  80224-2522
Saint Mary's Hospital and Regional Medical CenterGrand Junction, Colorado  81502
Saint Mary Corwin Medical CenterPueblo, Colorado  81004
Saint Francis Hospital and Medical CenterHartford, Connecticut  06105
Saint Joseph's-Candler Health SystemSavannah, Georgia  31405
Rush - Copley Medical CenterAurora, Illinois  60504
Joliet Oncology-Hematology Associates LimitedJoliet, Illinois  60435
Community Cancer Center FoundationNormal, Illinois  61761
Ottawa Regional Hospital and Healthcare CenterOttawa, Illinois  61350
Pekin Cancer Treatment CenterPekin, Illinois  61554
Illinois Oncology Research Association CCOPPeoria, Illinois  61615
Illinois CancerCare-PeoriaPeoria, Illinois  61615
Illinois Valley HospitalPeru, Illinois  61354
Saint Margaret's HospitalSpring Valley, Illinois  61362
Carle Clinic-Urbana MainUrbana, Illinois  61801
Wishard HospitalIndianapolis, Indiana  46202
Saint Anthony Memorial Health CenterMichigan City, Indiana  46360
McFarland ClinicAmes, Iowa  50010
Cedar Rapids Oncology AssociationCedar Rapids, Iowa  52403
Mercy HospitalCedar Rapids, Iowa  52403
Medical Oncology and Hematology Associates-West Des MoinesClive, Iowa  50325
Iowa Oncology Research Association CCOPDes Moines, Iowa  50309
Mercy Medical Center - Des MoinesDes Moines, Iowa  50314
Medical Oncology and Hematology Associates-Des MoinesDes Moines, Iowa  50309
Mercy Medical Center - North IowaMason City, Iowa  50401
Mercy Medical Center-Sioux CitySioux City, Iowa  51104
Saint Luke's Regional Medical CenterSioux City, Iowa  51104
Cancer Center of Kansas - El DoradoEl Dorado, Kansas  67042
Cancer Center of Kansas-KingmanKingman, Kansas  67068
Cancer Center of Kansas - ParsonsParsons, Kansas  67357
Cancer Center of Kansas - PrattPratt, Kansas  67124
Cancer Center of Kansas-Wichita Medical Arts TowerWichita, Kansas  67208
Cancer Center of Kansas - Main OfficeWichita, Kansas  67214
Michigan Cancer Research Consortium Community Clinical Oncology ProgramAnn Arbor, Michigan  48106
Oakwood HospitalDearborn, Michigan  48123
Saint John Hospital and Medical CenterDetroit, Michigan  48236
Allegiance HealthJackson, Michigan  49201
Sparrow HospitalLansing, Michigan  48912
Saint Mary Mercy HospitalLivonia, Michigan  48154
Saint Joseph Mercy OaklandPontiac, Michigan  48341-2985
Saint Joseph Mercy Port HuronPort Huron, Michigan  48060
Saint Mary's of MichiganSaginaw, Michigan  48601
Saint John Macomb-Oakland HospitalWarren, Michigan  48093
Miller-Dwan HospitalDuluth, Minnesota  55805
Unity HospitalFridley, Minnesota  55432
Saint John's Hospital - HealtheastMaplewood, Minnesota  55109
Minnesota Oncology Hematology PA-MaplewoodMaplewood, Minnesota  55109
North Memorial Medical Health CenterRobbinsdale, Minnesota  55422
Park Nicollet Clinic - Saint Louis ParkSaint Louis Park, Minnesota  55416
Minnesota Oncology and Hematology PA-WoodburyWoodbury, Minnesota  55125
Lincoln Medical Education Foundation Cancer Resource CenterLincoln, Nebraska  68510
Missouri Valley Cancer Consortium CCOPOmaha, Nebraska  68106
Nevada Cancer Research Foundation CCOPLas Vegas, Nevada  89106
Veterans Adminstration New Jersey Health Care SystemEast Orange, New Jersey  07018-1095
The North Division of Montefiore Medical CenterBronx, New York  10466
Aultman Health FoundationCanton, Ohio  44710
Doctors HospitalColumbus, Ohio  43228
Grant Medical CenterColumbus, Ohio  43215
Mount Carmel Health Center WestColumbus, Ohio  43222
Saint Rita's Medical CenterLima, Ohio  45801
Marietta Memorial HospitalMarietta, Ohio  45750
Genesis HealthCare SystemZanesville, Ohio  43701
Natalie W Bryant Cancer CenterTulsa, Oklahoma  74136
Saint Luke's HospitalBethlehem, Pennsylvania  18015
Geisinger Wyoming ValleyWilkes-Barre, Pennsylvania  18711
Mainline Health CCOPWynnewood, Pennsylvania  19096
Saint Vincent HospitalGreen Bay, Wisconsin  54301
Dean Hematology and Oncology ClinicMadison, Wisconsin  53717
Bay Area Medical CenterMarinette, Wisconsin  54143
Roger Maris Cancer CenterFargo, North Dakota  58122
Cancer Center of Kansas-LiberalLiberal, Kansas  67901
UMDNJ - New Jersey Medical SchoolNewark, New Jersey  07103
West Virginia University CharlestonCharleston, West Virginia  25304
Holy Family Memorial HospitalManitowoc, Wisconsin  54221
Hinsdale Hematology Oncology Associates IncorporatedHinsdale, Illinois  60521
Southern Ohio Medical CenterPortsmouth, Ohio  45662
Gundersen LutheranLa Crosse, Wisconsin  54601
Saint Nicholas HospitalMadison, Wisconsin  53715
Alegent Health Lakeside HospitalOmaha, Nebraska  68130
New York Oncology Hematology PC -Albany Medical CenterAlbany, New York  12208
Siouxland Hematology Oncology AssociatesSioux City, Iowa  51101
Carle Foundation - Carle Cancer CenterUrbana, Illinois  61801
Oncology Associates at Mercy Medical CenterCedar Rapids, Iowa  52403
Sanford Clinic North-FargoFargo, North Dakota  58102
Sanford Medical Center-FargoFargo, North Dakota  58122
Summa Akron City HospitalAkron, Ohio  44304
Genesys Regional Medical Center-West Flint CampusFlint, Michigan  48532
Sanford Clinic North-BemidgiBemidji, Minnesota  56601
Essentia Health Duluth Clinic CCOPDuluth, Minnesota  55805
Essentia Health Saint Mary's Medical CenterDuluth, Minnesota  55805
Geisinger Medical Center-Cancer Center HazeltonHazleton, Pennsylvania  18201
Springfield Regional Medical CenterSpringfield, Ohio  45505
Lake Region Healthcare Corporation-Cancer CareFergus Falls, Minnesota  56537
Nevada Cancer Institute-Summerlin CampusLas Vegas, Nevada  89135
Cancer Center of Western WisconsinNew Richmond, Wisconsin  54017