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: September 19, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Clear Cell Renal Cell Carcinoma
Recurrent Renal Cell Cancer
Stage III Renal Cell Cancer
Stage IV Renal Cell Cancer
Biological: ziv-aflibercept
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 120
Study Start Date: December 2007
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (higher dose of ziv-aflibercept)
Patients receive a higher dose of ziv-aflibercept IV over 1 hour on day 1.
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 B (lower dose of ziv-aflibercept)
Patients receive a lower dose of ziv-aflibercept IV over 1 hour on day 1.
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

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00357760

  Show 206 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Roberto Pili ECOG-ACRIN Cancer Research Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00357760     History of Changes
Other Study ID Numbers: NCI-2009-00559, NCI-2009-00559, ECOG-E4805, CDR0000489069, E4805, E4805, U10CA021115, U10CA180820
Study First Received: July 26, 2006
Last Updated: September 19, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Carcinoma
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Endothelial Growth Factors
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014