Ziv-Aflibercept in Treating Patients With Metastatic or Unresectable Kidney Cancer

May 30, 2017 updated by: National Cancer Institute (NCI)

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

This randomized phase II trial studies how well ziv-aflibercept (VEGF Trap) works in treating patients with kidney cancer that has spread from the primary site to other places in the body (metastatic) or is unable to be removed with surgery (unresectable). Ziv-aflibercept may stop the growth of kidney cancer by blocking blood flow to the tumor.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the effect of two different doses of AVE0005 (vascular endothelial growth factor [VEGF] Trap [ziv-aflibercept]) 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. To 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. To describe progression-free survival among patients who undergo dose escalation following progression on low-dose AVE0005 (VEGF Trap).

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

OTHER PRE-SPECIFIED OBJECTIVES:

I. To determine the circulating levels of VEGF AVE0005 (VEGF-Trap) complex and correlate it with clinical activity.

II. To evaluate the modulation of specific angiogenesis-related protein expression by AVE0005 (VEGF Trap).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

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

ARM B (Lower dose of VEGF Trap): Patients receive a lower dose of ziv-aflibercept 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 B may crossover and receive treatment on Arm A at the time of disease progression.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 1 year.

Study Type

Interventional

Enrollment (Actual)

94

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Peru
      • Lima, Peru, Lima 34
        • Instituto Nacional de Enfermedades Neoplasicas
  • United States
    • Colorado
      • Aurora, Colorado, United States, 80012
        • The Medical Center of Aurora
      • Boulder, Colorado, United States, 80301
        • Boulder Community Hospital
      • Colorado Springs, Colorado, United States, 80907
        • Penrose-Saint Francis Healthcare
      • Denver, Colorado, United States, 80210
        • Porter Adventist Hospital
      • Denver, Colorado, United States, 80218
        • Presbyterian - Saint Lukes Medical Center - Health One
      • Denver, Colorado, United States, 80218
        • SCL Health Saint Joseph Hospital
      • Denver, Colorado, United States, 80220
        • Rose Medical Center
      • Denver, Colorado, United States, 80222
        • Colorado Cancer Research Program NCORP
      • Englewood, Colorado, United States, 80113
        • Swedish Medical Center
      • Grand Junction, Colorado, United States, 81502
        • Saint Mary's Hospital and Regional Medical Center
      • Greeley, Colorado, United States, 80631
        • North Colorado Medical Center
      • Lakewood, Colorado, United States, 80228
        • Saint Anthony Hospital
      • Littleton, Colorado, United States, 80122
        • Littleton Adventist Hospital
      • Lone Tree, Colorado, United States, 80124
        • Sky Ridge Medical Center
      • Longmont, Colorado, United States, 80501
        • Longmont United Hospital
      • Loveland, Colorado, United States, 80539
        • McKee Medical Center
      • Parker, Colorado, United States, 80138
        • Parker Adventist Hospital
      • Pueblo, Colorado, United States, 81004
        • Saint Mary Corwin Medical Center
      • Thornton, Colorado, United States, 80229
        • North Suburban Medical Center
      • Wheat Ridge, Colorado, United States, 80033
        • SCL Health Lutheran Medical Center
    • Connecticut
      • Hartford, Connecticut, United States, 06105
        • Smilow Cancer Hospital Care Center at Saint Francis
      • Manchester, Connecticut, United States, 06040
        • Manchester Memorial Hospital
      • Norwich, Connecticut, United States, 06360
        • Eastern Connecticut Hematology and Oncology Associates
    • District of Columbia
      • Washington, D.C., District of Columbia, United States, 20016
        • Sibley Memorial Hospital
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University/Winship Cancer Institute
      • Savannah, Georgia, United States, 31405
        • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
    • Idaho
      • Boise, Idaho, United States, 83706
        • Saint Alphonsus Cancer Care Center-Boise
    • Illinois
      • Aurora, Illinois, United States, 60504
        • Rush - Copley Medical Center
      • Bloomington, Illinois, United States, 61701
        • Saint Joseph Medical Center
      • Canton, Illinois, United States, 61520
        • Graham Hospital Association
      • Carthage, Illinois, United States, 62321
        • Memorial Hospital
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital
      • Decatur, Illinois, United States, 62526
        • Heartland Cancer Research NCORP
      • Eureka, Illinois, United States, 61530
        • Eureka Hospital
      • Galesburg, Illinois, United States, 61401
        • Illinois CancerCare-Galesburg
      • Galesburg, Illinois, United States, 61401
        • Galesburg Cottage Hospital
      • Galesburg, Illinois, United States, 61401
        • Illinois CancerCare-Galesburg Cottage Plaza Office
      • Havana, Illinois, United States, 62644
        • Mason District Hospital
      • Hinsdale, Illinois, United States, 60521
        • Hinsdale Hematology Oncology Associates Incorporated
      • Joliet, Illinois, United States, 60435
        • Joliet Oncology-Hematology Associates Limited
      • Macomb, Illinois, United States, 61455
        • Mcdonough District Hospital
      • Normal, Illinois, United States, 61761
        • Community Cancer Center Foundation
      • Normal, Illinois, United States, 61761
        • Bromenn Regional Medical Center
      • Ottawa, Illinois, United States, 61350
        • Ottawa Regional Hospital and Healthcare Center
      • Pekin, Illinois, United States, 61554
        • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
      • Pekin, Illinois, United States, 61554
        • Pekin Hospital
      • Peoria, Illinois, United States, 61637
        • OSF Saint Francis Medical Center
      • Peoria, Illinois, United States, 61615
        • Illinois CancerCare-Peoria
      • Peoria, Illinois, United States, 61614
        • Proctor Hospital
      • Peoria, Illinois, United States, 61603
        • Methodist Medical Center of Illinois
      • Peru, Illinois, United States, 61354
        • Illinois Valley Hospital
      • Princeton, Illinois, United States, 61356
        • Perry Memorial Hospital
      • Rockford, Illinois, United States, 61114
        • SwedishAmerican Regional Cancer Center/ACT
      • Spring Valley, Illinois, United States, 61362
        • Saint Margaret's Hospital
      • Springfield, Illinois, United States, 62781
        • Memorial Medical Center
      • Urbana, Illinois, United States, 61801
        • Carle Cancer Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University/Melvin and Bren Simon Cancer Center
      • Indianapolis, Indiana, United States, 46202
        • Sidney and Lois Eskenazi Hospital
      • Michigan City, Indiana, United States, 46360
        • Franciscan Saint Anthony Health-Michigan City
    • Iowa
      • Ames, Iowa, United States, 50010
        • McFarland Clinic PC-William R Bliss Cancer Center
      • Cedar Rapids, Iowa, United States, 52403
        • Mercy Hospital
      • Cedar Rapids, Iowa, United States, 52403
        • Oncology Associates at Mercy Medical Center
      • Clive, Iowa, United States, 50325
        • Medical Oncology and Hematology Associates-West Des Moines
      • Des Moines, Iowa, United States, 50309
        • Iowa Methodist Medical Center
      • Des Moines, Iowa, United States, 50314
        • Mercy Medical Center - Des Moines
      • Des Moines, Iowa, United States, 50309
        • Medical Oncology and Hematology Associates-Des Moines
      • Des Moines, Iowa, United States, 50316
        • Iowa Lutheran Hospital
      • Des Moines, Iowa, United States, 50309
        • Iowa-Wide Oncology Research Coalition NCORP
      • Des Moines, Iowa, United States, 50314
        • Medical Oncology and Hematology Associates-Laurel
      • Mason City, Iowa, United States, 50401
        • Mercy Medical Center - North Iowa
      • Ottumwa, Iowa, United States, 52501
        • Ottumwa Regional Health Center
      • Sioux City, Iowa, United States, 51101
        • Siouxland Regional Cancer Center
      • Sioux City, Iowa, United States, 51104
        • Saint Luke's Regional Medical Center
      • Sioux City, Iowa, United States, 51104
        • Mercy Medical Center-Sioux City
    • Kansas
      • Chanute, Kansas, United States, 66720
        • Cancer Center of Kansas - Chanute
      • Dodge City, Kansas, United States, 67801
        • Cancer Center of Kansas - Dodge City
      • El Dorado, Kansas, United States, 67042
        • Cancer Center of Kansas - El Dorado
      • Fort Scott, Kansas, United States, 66701
        • Cancer Center of Kansas - Fort Scott
      • Independence, Kansas, United States, 67301
        • Cancer Center of Kansas-Independence
      • Kingman, Kansas, United States, 67068
        • Cancer Center of Kansas-Kingman
      • Lawrence, Kansas, United States, 66044
        • Lawrence Memorial Hospital
      • Liberal, Kansas, United States, 67905
        • Cancer Center of Kansas-Liberal
      • McPherson, Kansas, United States, 67460
        • Cancer Center of Kansas - McPherson
      • Newton, Kansas, United States, 67114
        • Cancer Center of Kansas - Newton
      • Parsons, Kansas, United States, 67357
        • Cancer Center of Kansas - Parsons
      • Pratt, Kansas, United States, 67124
        • Cancer Center of Kansas - Pratt
      • Salina, Kansas, United States, 67401
        • Cancer Center of Kansas - Salina
      • Wellington, Kansas, United States, 67152
        • Cancer Center of Kansas - Wellington
      • Wichita, Kansas, United States, 67208
        • Cancer Center of Kansas-Wichita Medical Arts Tower
      • Wichita, Kansas, United States, 67214
        • Cancer Center of Kansas - Wichita
      • Wichita, Kansas, United States, 67208
        • Associates In Womens Health
      • Wichita, Kansas, United States, 67214
        • Wichita NCI Community Oncology Research Program
      • Wichita, Kansas, United States, 67214
        • Via Christi Regional Medical Center
      • Winfield, Kansas, United States, 67156
        • Cancer Center of Kansas - Winfield
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University/Sidney Kimmel Cancer Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48106-0995
        • Saint Joseph Mercy Hospital
      • Ann Arbor, Michigan, United States, 48106
        • Michigan Cancer Research Consortium NCORP
      • Dearborn, Michigan, United States, 48124
        • Beaumont Hospital-Dearborn
      • Detroit, Michigan, United States, 48236
        • Saint John Hospital and Medical Center
      • Flint, Michigan, United States, 48502
        • Hurley Medical Center
      • Flint, Michigan, United States, 48532
        • Genesys Regional Medical Center-West Flint Campus
      • Flint, Michigan, United States, 48503
        • Genesys Hurley Cancer Institute
      • Jackson, Michigan, United States, 49201
        • Allegiance Health
      • Kalamazoo, Michigan, United States, 49007
        • West Michigan Cancer Center
      • Kalamazoo, Michigan, United States, 49007
        • Bronson Methodist Hospital
      • Kalamazoo, Michigan, United States, 49001
        • Borgess Medical Center
      • Lansing, Michigan, United States, 48912
        • Sparrow Hospital
      • Livonia, Michigan, United States, 48154
        • Saint Mary Mercy Hospital
      • Pontiac, Michigan, United States, 48341
        • Saint Joseph Mercy Oakland
      • Port Huron, Michigan, United States, 48060
        • Saint Joseph Mercy Port Huron
      • Saginaw, Michigan, United States, 48601
        • Saint Mary's of Michigan
      • Warren, Michigan, United States, 48093
        • Saint John Macomb-Oakland Hospital
    • Minnesota
      • Bemidji, Minnesota, United States, 56601
        • Sanford Clinic North-Bemidgi
      • Burnsville, Minnesota, United States, 55337
        • Fairview Ridges Hospital
      • Coon Rapids, Minnesota, United States, 55433
        • Mercy Hospital
      • Duluth, Minnesota, United States, 55805
        • Essentia Health Cancer Center
      • Duluth, Minnesota, United States, 55805
        • Essentia Health Saint Mary's Medical Center
      • Duluth, Minnesota, United States, 55805
        • Miller-Dwan Hospital
      • Edina, Minnesota, United States, 55435
        • Fairview-Southdale Hospital
      • Fergus Falls, Minnesota, United States, 56537
        • Lake Region Healthcare Corporation-Cancer Care
      • Fridley, Minnesota, United States, 55432
        • Unity Hospital
      • Hutchinson, Minnesota, United States, 55350
        • Hutchinson Area Health Care
      • Maplewood, Minnesota, United States, 55109
        • Saint John's Hospital - Healtheast
      • Maplewood, Minnesota, United States, 55109
        • Minnesota Oncology Hematology PA-Maplewood
      • Minneapolis, Minnesota, United States, 55415
        • Hennepin County Medical Center
      • Minneapolis, Minnesota, United States, 55407
        • Abbott-Northwestern Hospital
      • New Ulm, Minnesota, United States, 56073
        • New Ulm Medical Center
      • Robbinsdale, Minnesota, United States, 55422
        • North Memorial Medical Health Center
      • Saint Louis Park, Minnesota, United States, 55416
        • Park Nicollet Clinic - Saint Louis Park
      • Saint Louis Park, Minnesota, United States, 55416
        • Metro Minnesota Community Oncology Research Consortium
      • Saint Paul, Minnesota, United States, 55101
        • Regions Hospital
      • Saint Paul, Minnesota, United States, 55102
        • United Hospital
      • Shakopee, Minnesota, United States, 55379
        • Saint Francis Regional Medical Center
      • Stillwater, Minnesota, United States, 55082
        • Lakeview Hospital
      • Waconia, Minnesota, United States, 55387
        • Ridgeview Medical Center
      • Willmar, Minnesota, United States, 56201
        • Rice Memorial Hospital
      • Woodbury, Minnesota, United States, 55125
        • Minnesota Oncology and Hematology PA-Woodbury
    • Nebraska
      • Lincoln, Nebraska, United States, 68510
        • Nebraska Cancer Research Center
      • Omaha, Nebraska, United States, 68124
        • Alegent Health Bergan Mercy Medical Center
      • Omaha, Nebraska, United States, 68122
        • Alegent Health Immanuel Medical Center
      • Omaha, Nebraska, United States, 68130
        • Alegent Health Lakeside Hospital
      • Omaha, Nebraska, United States, 68131
        • Creighton University Medical Center
      • Omaha, Nebraska, United States, 68106
        • Missouri Valley Cancer Consortium
    • Nevada
      • Las Vegas, Nevada, United States, 89106
        • Nevada Cancer Research Foundation CCOP
      • Las Vegas, Nevada, United States, 89135
        • Nevada Cancer Institute-Summerlin Campus
    • New Jersey
      • East Orange, New Jersey, United States, 07018-1095
        • Veterans Adminstration New Jersey Health Care System
      • Newark, New Jersey, United States, 07101
        • Rutgers New Jersey Medical School
    • New York
      • Albany, New York, United States, 12208
        • New York Oncology Hematology PC -Albany Medical Center
      • Cooperstown, New York, United States, 13326
        • Mary Imogene Bassett Hospital
      • New York, New York, United States, 10003
        • Beth Israel Medical Center
      • The Bronx, New York, United States, 10466
        • Montefiore Medical Center-Wakefield Campus
    • North Dakota
      • Fargo, North Dakota, United States, 58122
        • Sanford Clinic North-Fargo
      • Fargo, North Dakota, United States, 58122
        • Sanford Medical Center-Fargo
      • Fargo, North Dakota, United States, 58122
        • Roger Maris Cancer Center
    • Ohio
      • Akron, Ohio, United States, 44304
        • Summa Akron City Hospital/Cooper Cancer Center
      • Bellefontaine, Ohio, United States, 43311
        • Mary Rutan Hospital
      • Belpre, Ohio, United States, 45714
        • Strecker Cancer Center-Belpre
      • Canton, Ohio, United States, 44710
        • Aultman Health Foundation
      • Chillicothe, Ohio, United States, 45601
        • Adena Regional Medical Center
      • Cleveland, Ohio, United States, 44109
        • MetroHealth Medical Center
      • Columbus, Ohio, United States, 43214
        • Riverside Methodist Hospital
      • Columbus, Ohio, United States, 43214
        • Columbus Oncology and Hematology Associates Inc
      • Columbus, Ohio, United States, 43228
        • Doctors Hospital
      • Columbus, Ohio, United States, 43215
        • Grant Medical Center
      • Columbus, Ohio, United States, 43222
        • Mount Carmel Health Center West
      • Columbus, Ohio, United States, 43215
        • Columbus NCI Community Oncology Research Program
      • Delaware, Ohio, United States, 43015
        • Delaware Health Center-Grady Cancer Center
      • Delaware, Ohio, United States, 43015
        • Grady Memorial Hospital
      • Lancaster, Ohio, United States, 43130
        • Fairfield Medical Center
      • Lima, Ohio, United States, 45801
        • Saint Rita's Medical Center
      • Marietta, Ohio, United States, 45750
        • Marietta Memorial Hospital
      • Mount Vernon, Ohio, United States, 43050
        • Knox Community Hospital
      • Newark, Ohio, United States, 43055
        • Licking Memorial Hospital
      • Portsmouth, Ohio, United States, 45662
        • Southern Ohio Medical Center
      • Springfield, Ohio, United States, 45505
        • Springfield Regional Medical Center
      • Steubenville, Ohio, United States, 43952
        • Trinity's Tony Teramana Cancer Center
      • Zanesville, Ohio, United States, 43701
        • Genesis Healthcare System Cancer Care Center
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74136
        • Natalie Warren Bryant Cancer Center at Saint Francis
    • Pennsylvania
      • Bethlehem, Pennsylvania, United States, 18015
        • Saint Luke's University Hospital-Bethlehem Campus
      • Bryn Mawr, Pennsylvania, United States, 19010
        • Bryn Mawr Hospital
      • Danville, Pennsylvania, United States, 17822
        • Geisinger Medical Center
      • Hazleton, Pennsylvania, United States, 18201
        • Geisinger Medical Center-Cancer Center Hazleton
      • Paoli, Pennsylvania, United States, 19301
        • Paoli Memorial Hospital
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Cancer Institute (UPCI)
      • State College, Pennsylvania, United States, 16801
        • Geisinger Medical Group
      • Wilkes-Barre, Pennsylvania, United States, 18711
        • Geisinger Wyoming Valley/Henry Cancer Center
      • Wynnewood, Pennsylvania, United States, 19096
        • Lankenau Medical Center
      • Wynnewood, Pennsylvania, United States, 19096
        • Main Line Health NCORP
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57105
        • Avera Cancer Institute
      • Sioux Falls, South Dakota, United States, 57105
        • Avera McKennan Hospital and University Health Center
    • Texas
      • Temple, Texas, United States, 76508
        • Scott and White Memorial Hospital
    • West Virginia
      • Charleston, West Virginia, United States, 25304
        • West Virginia University Charleston
    • Wisconsin
      • Green Bay, Wisconsin, United States, 54301
        • Saint Vincent Hospital
      • Johnson Creek, Wisconsin, United States, 53038
        • UW Cancer Center Johnson Creek
      • La Crosse, Wisconsin, United States, 54601
        • Gundersen Lutheran Medical Center
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Hospital and Clinics
      • Madison, Wisconsin, United States, 53717
        • Dean Hematology and Oncology Clinic
      • Manitowoc, Wisconsin, United States, 54221
        • Holy Family Memorial Hospital
      • Marinette, Wisconsin, United States, 54143
        • Bay Area Medical Center
      • New Richmond, Wisconsin, United States, 54017
        • Cancer Center of Western Wisconsin
      • Sheboygan, Wisconsin, United States, 53081
        • Saint Nicholas Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically confirmed metastatic or unresectable renal cell carcinoma; disease must be conventional clear cell carcinoma or have a component of clear cell carcinoma
  • Patient must have measurable lesions according to the Response Evaluation Criteria In Solid Tumors (RECIST); baseline measurements must be performed =< 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
  • 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
  • Adequate organ function as defined in the protocol
  • 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

Exclusion Criteria:

  • True papillary, sarcomatoid features without any clear cell component, chromophobe, oncocytoma, collecting duct tumors and transitional cell carcinoma are not eligible
  • Prior immunotherapy other than cytokine therapy with interleukin 2 and interferon alpha
  • Prior treatment with bevacizumab
  • Prior cellular therapy, vaccine, hormonal or chemotherapy for renal cell carcinoma; prior therapy for other cancers is allowable if therapy ended at least 5 years prior to enrollment
  • History of metastatic central nervous system (CNS) disease
  • Pregnant or breastfeeding
  • 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 within 24 weeks prior to randomization
  • Prior pulmonary embolism, deep vein thrombosis, or other thromboembolic event
  • 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
  • Active infection, evidence of bleeding or intratumoral bleeding, or underlying bleeding disorder
  • History of hypersensitivity to any Trap agents or recombinant proteins
  • Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A (higher dose of VEGF Trap)
Patients receive a higher dose of ziv-aflibercept (VEGF Trap) IV over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Biological: VEGF Trap
Given IV
Other Names:
  • AVE0005
  • Vascular Endothelial Growth Factor Trap
  • Ziv-Aflibercept
Experimental: Arm B (lower dose of VEGF Trap)
Patients receive a lower dose of ziv-aflibercept (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. At the time of disease progression, the dose of ziv-aflibercept (VEGF Trap) may be escalated to the higher dose in Arm A.
Biological: VEGF Trap
Given IV
Other Names:
  • AVE0005
  • Vascular Endothelial Growth Factor Trap
  • Ziv-Aflibercept

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Patients Alive and Progression-free at 8 Weeks
Time Frame: Assessed at 8 weeks

Progression-free survival (PFS) was defined as time from randomization to the earlier of documentation of progression or death. The proportion of patients who are progression-free and alive at 8 weeks was estimated using the Kaplan-Meier method and the confidence interval was estimated using log transformation method.

Progression is defined using Response Evaluation Criteria In Solid Tumors (RECIST), as a 20% increase in the sum of the longest diameters of target lesions, or the appearance of new lesions, or unequivocal progression of existing nontarget lesions.
Assessed at 8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Patients With Objective Response
Time Frame: Assessed every 8 weeks while on treatment and then every 3 months until patient is 2 years from enrollment, and then every 6 months until patient is 3 years from enrollment

Objective response is defined as complete response (CR) or partial response (PR) determined by Solid Tumor Response Criteria (RECIST).

CR: The disappearance of all target lesions without the appearance of new lesion(s) and/or unequivocal progression of existing non-target lesions.

PR: At least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter without the appearance of new lesion(s) and/or unequivocal progression of existing non-target lesions.

To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no less than four weeks after the criteria for response are first met.
Assessed every 8 weeks while on treatment and then every 3 months until patient is 2 years from enrollment, and then every 6 months until patient is 3 years from enrollment
Progression-free Survival (PFS) Among Patients Who Undergo Dose Escalation Following Progression on Lower-dose VEGF Trap
Time Frame: Assessed every 8 weeks while on treatment and then every 3 months until patient is 2 years from enrollment, and then every 6 months until patient is 3 years from enrollment

Patients who progressed on the 1 mg/kg dose (Arm B) at 8 weeks would have the opportunity to receive the 4 mg/kg dose. PFS is defined as the time from dose escalation to disease progression or death, whichever occurs first.

Disease progression is defined using Response Evaluation Criteria In Solid Tumors (RECIST), as a 20% increase in the sum of the longest diameters of target lesions, or the appearance of new lesions, or unequivocal progression of existing nontarget lesions.
Assessed every 8 weeks while on treatment and then every 3 months until patient is 2 years from enrollment, and then every 6 months until patient is 3 years from enrollment

Other Outcome Measures

Outcome Measure
Time Frame
Circulating Levels of VEGF-Trap Complex
Time Frame: Assessed at baseline, 4 weeks, 6 weeks, 8 weeks and end of treatment
Assessed at baseline, 4 weeks, 6 weeks, 8 weeks and end of treatment
Angiogenesis-related Protein Expression
Time Frame: Assessed every 8 weeks during treatment and end of treatment
Assessed every 8 weeks during treatment and end of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Roberto Pili, ECOG-ACRIN Cancer Research Group

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2007

Primary Completion (Actual)

October 1, 2015

Study Completion (Actual)

October 1, 2015

Study Registration Dates

First Submitted

July 26, 2006

First Submitted That Met QC Criteria

July 26, 2006

First Posted (Estimate)

July 27, 2006

Study Record Updates

Last Update Posted (Actual)

June 23, 2017

Last Update Submitted That Met QC Criteria

May 30, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2009-00559 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180820 (U.S. NIH Grant/Contract)
  • U10CA021115 (U.S. NIH Grant/Contract)
  • E4805 (Other Identifier: ECOG-ACRIN Cancer Research Group)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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