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

• ClinicalTrials.gov Identifier: NCT00357760
• Recruitment Status: Completed
• First Posted: July 27, 2006
• Results First Posted: April 4, 2017
• Last Update Posted: June 23, 2017
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Tracking Information

• First Submitted Date: July 26, 2006
• First Posted Date: July 27, 2006
• Results First Submitted Date: February 8, 2017
• Results First Posted Date: April 4, 2017
• Last Update Posted Date: June 23, 2017
• Study Start Date: December 2007
• Actual Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 7, 2017)

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.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: April 7, 2017)

• 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.
• 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.

• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: February 8, 2017)

• Circulating Levels of VEGF-Trap Complex [ Time Frame: 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 ]

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Ziv-Aflibercept in Treating Patients With Metastatic or Unresectable Kidney Cancer
• 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
• Brief Summary: 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.

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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Renal Cell Carcinoma

Intervention

Biological: VEGF Trap

Given IV

Other Names:

• AVE0005
• Vascular Endothelial Growth Factor Trap
• Ziv-Aflibercept

Study Arms

• 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.
  Intervention: Biological: VEGF Trap
• 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.
  Intervention: Biological: VEGF Trap

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 8, 2017): 94
• Original Enrollment: Not Provided
• Actual Study Completion Date: October 2015
• Actual Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Peru, United States

Administrative Information

• NCT Number: NCT00357760
• Other Study ID Numbers: NCI-2009-00559; NCI-2009-00559 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); E4805 ( Other Identifier: ECOG-ACRIN Cancer Research Group ); U10CA180820 ( U.S. NIH Grant/Contract ); U10CA021115 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.

• Responsible Party: National Cancer Institute (NCI)
• Study Sponsor: National Cancer Institute (NCI)
• Collaborators: Not Provided

Investigators

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

• PRS Account: National Cancer Institute (NCI)
• Verification Date: May 2017