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

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIBiomarker/Laboratory analysis, TreatmentClosed18 and overNCINCI-2009-00559
ECOG-E4805, CDR0000489069, E4805, U10CA180820, U10CA021115, NCT00357760

Trial Description


This randomized phase II trial studies how well ziv-aflibercept 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.

Further Study Information


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).


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.

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

V. 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: Patients receive a higher dose of ziv-aflibercept intervenously (IV) over 1 hour on day 1.

ARM B: 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 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 2 years and then every 6 months for 1 year.

Eligibility Criteria

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 glutamate 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 known history of metastatic central nervous system (CNS) disease
  • Female patients MUST NOT be pregnant or breastfeeding; 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
  • Patients must not have had a 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

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

    Roberto Pili, Principal Investigator

    Trial Sites



    Genesys Hurley Cancer Institute

    Philip J. Stella
    Ph: 734-712-3456

    Las Vegas

    Nevada Cancer Institute

    Oscar B Goodman
    Ph: 702-822-5136

    New York

    New York Oncology Hematology, PC at Albany Medical Center

    Charles H Weissman
    Ph: 518-489-3612ext1342
    Email: sharon.krause@usoncology.com


    Bassett Healthcare Regional Cancer Program at Mary Imogene Bassett Hospital

    Eric Bravin
    Ph: 607-547-6965
    Email: jennifer.victory@bassett.org

    Bryn Mawr

    Bryn Mawr Hospital

    Paul B. Gilman
    Ph: 484-476-2649
    Email: wellenbachj@mlhs.org


    Cancer Center of Paoli Memorial Hospital

    Paul B. Gilman
    Ph: 484-476-2649
    Email: wellenbachj@mlhs.org


    CCOP - Main Line Health

    Paul B. Gilman
    Ph: 484-476-2649
    Email: wellenbachj@mlhs.org

    Lankenau Cancer Center at Lankenau Hospital

    Paul B. Gilman
    Ph: 484-476-2649
    Email: wellenbachj@mlhs.org

    South Dakota
    Sioux Falls

    Avera Cancer Institute

    Addison R Tolentino
    Ph: 800-657-4377
    Email: Jan.Healy@avera.org

    West Virginia

    West Virginia University Medical School - Charleston

    Steven J. Jubelirer
    Ph: 304-388-9944

    Link to the current ClinicalTrials.gov record.
    NLM Identifier NCT00357760
    ClinicalTrials.gov processed this data on May 27, 2015

    Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.