This trial is active, not recruiting.

Conditions clear cell renal cell carcinoma, recurrent renal cell carcinoma, stage iii renal cell cancer, stage iv renal cell cancer
Treatments laboratory biomarker analysis, pharmacological study, ziv-aflibercept
Phase phase 2
Sponsor National Cancer Institute (NCI)
Start date December 2007
End date October 2016
Trial size 120 participants
Trial identifier NCT00357760, CDR0000489069, E4805, ECOG-E4805, NCI-2009-00559, U10CA021115, U10CA180820


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model crossover assignment
Masking open label
Primary purpose treatment
Patients receive a higher dose of ziv-aflibercept IV over 1 hour on day 1.
laboratory biomarker analysis
Correlative studies
pharmacological study
Correlative studies
ziv-aflibercept AFLIBERCEPT
Given IV
Patients receive a lower dose of ziv-aflibercept IV over 1 hour on day 1.
laboratory biomarker analysis
Correlative studies
pharmacological study
Correlative studies
ziv-aflibercept AFLIBERCEPT
Given IV

Primary Outcomes

Progression-free survival rate as assessed by Response Evaluation Criteria in Solid Tumors
time frame: Time from randomization to the earlier of documentation of progression or death, assessed at 8 weeks

Secondary Outcomes

Incidence of adverse events as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
time frame: Up to 30 days after the last dose of treatment
Overall survival
time frame: Up to 3 years
Response duration
time frame: From the time that measurement criteria are met for complete or partial response until the first date that recurrent or progressive disease is objectively documented, assessed up to 3 years
Response rate
time frame: Up to 3 years

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title A Randomized Phase II Study to Determine the Effect of 2 Different Doses of AVE0005 (VEGF Trap) in Patients With Metastatic Renal Cell Carcinoma
Principal investigator Roberto Pili
Description PRIMARY OBJECTIVES: 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. 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.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).