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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00357760
First received: July 26, 2006
Last updated: August 26, 2014
Last verified: May 2014

July 26, 2006
August 26, 2014
December 2007
October 2016   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00357760 on ClinicalTrials.gov Archive Site
  • Response rate [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Ziv-Aflibercept in Treating Patients With Metastatic or Unresectable Kidney Cancer
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 works in treating patients with metastatic or unresectable kidney cancer. Ziv-aflibercept may stop the growth of kidney cancer by blocking blood flow to the tumor.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Clear Cell Renal Cell Carcinoma
  • Recurrent Renal Cell Cancer
  • Stage III Renal Cell Cancer
  • Stage IV Renal Cell Cancer
  • Biological: ziv-aflibercept
    Given IV
    Other Names:
    • aflibercept
    • vascular endothelial growth factor trap
    • VEGF Trap
    • Zaltrap
  • Other: laboratory biomarker analysis
    Correlative studies
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
  • Experimental: Arm A (higher dose of ziv-aflibercept)
    Patients receive a higher dose of ziv-aflibercept IV over 1 hour on day 1.
    Interventions:
    • Biological: ziv-aflibercept
    • Other: laboratory biomarker analysis
    • Other: pharmacological study
  • Experimental: Arm B (lower dose of ziv-aflibercept)
    Patients receive a lower dose of ziv-aflibercept IV over 1 hour on day 1.
    Interventions:
    • Biological: ziv-aflibercept
    • Other: laboratory biomarker analysis
    • Other: pharmacological study
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
120
Not Provided
October 2016   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Peru
 
NCT00357760
NCI-2009-00559, NCI-2009-00559, ECOG-E4805, CDR0000489069, E4805, E4805, U10CA021115, U10CA180820
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Roberto Pili ECOG-ACRIN Cancer Research Group
National Cancer Institute (NCI)
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP