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VEGF Trap in Treating Patients With Recurrent, Locally Advanced, or Metastatic Cancer of the Urothelium

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00407485
Recruitment Status : Completed
First Posted : December 5, 2006
Results First Posted : October 3, 2014
Last Update Posted : October 20, 2014
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase II trial is studying the side effects and how well VEGF Trap works in treating patients with recurrent, locally advanced, or metastatic cancer of the urothelium. VEGF Trap may stop the growth of tumor cells by blocking blood flow to the tumor.

Condition or disease Intervention/treatment Phase
Adenocarcinoma of the Bladder Distal Urethral Cancer Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter Proximal Urethral Cancer Recurrent Bladder Cancer Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter Recurrent Urethral Cancer Squamous Cell Carcinoma of the Bladder Stage III Bladder Cancer Stage III Urethral Cancer Stage IV Bladder Cancer Transitional Cell Carcinoma of the Bladder Urethral Cancer Associated With Invasive Bladder Cancer Biological: ziv-aflibercept Other: pharmacological study Phase 2

Detailed Description:


I. Determine the response rate in patients with recurrent, locoregionally advanced, or metastatic transitional cell carcinoma of the urothelium treated with VEGF Trap.

II. Determine the time to progression in patients treated with this drug. III. Determine overall survival of patients treated with this drug. IV. Determine the tolerability and safety of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive VEGF Trap IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection periodically during study for pharmacokinetic/pharmacodynamic correlative studies.

After completion of study treatment, patients are followed periodically.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of VEGF Trap (NSC 724770) in Patients With Recurrent or Metastatic Transitional Carcinoma of the Urothelium
Study Start Date : November 2006
Actual Primary Completion Date : April 2010
Actual Study Completion Date : April 2014

Arm Intervention/treatment
Experimental: Treatment (ziv-aflibercept)
Patients receive 4 mg/kg VEGF Trap IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Biological: ziv-aflibercept
Given IV

Other: pharmacological study
Correlative studies

Primary Outcome Measures :
  1. Tumor Response Rate [ Time Frame: From the start of the treatment until disease progression or recurrence, assessed up to 4 years ]

    Response rate (RR) and progression free survival (PFS) were assessed in a 2-stage accrual design (22+18). A maximum of 40 patients were to be accrued to rule out a null hypothesized RR of 4% and PFS of 3 months versus alternative of 15% RR and 5.4 months PFS (corresponding to 4 month PFS of 40% vs 60%) with α=0.12 and β=0.19. If no more than 1 objective response (no more than 4.5%), and no more than 10 instances of 4-month PFS (no more than 45%), were observed among the initial 22 patients, the study would be terminated early and declared negative. Tumor response was evaluated by CT or MRI using RECIST v1.0 criteria.

    Responders were confirmed partial or complete responses to treatment.

  2. Progression-free Survival (PFS) [ Time Frame: From start of treatment to time of progression, assessed up to 4 months ]
    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions PFS using the product-limit method of Kaplan and Meier.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed transitional cell carcinoma (TCC) of the urothelium

    • Must have predominance of transitional histology, but foci of squamous and/or adenocarcinoma histology allowed
    • Poorly differentiated transitional cell carcinoma allowed
  • TCC of any of the following sites allowed:

    • Bladder
    • Renal pelvis
    • Ureter
    • Urethra
  • Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan
  • Locoregionally advanced or metastatic disease that is not amenable to curative surgery and/or radiotherapy
  • Must have received 1 prior systemic chemotherapy regimen containing a platinum compound (e.g., cisplatin, carboplatin, or oxaliplatin) in the neoadjuvant, adjuvant, or metastatic setting
  • No evidence of CNS disease, including primary brain tumor or brain metastases
  • ECOG performance status 0-2
  • Absolute neutrophil count >= 1,000/mm^3
  • Platelet count >= 75,000/mm^3
  • Bilirubin =< 1.5 times upper limit of normal (ULN)
  • AST or ALT =< 2.5 times ULN
  • Creatinine =< 2.5 times ULN OR creatinine clearance => 40 mL/min
  • Urine protein: creatinine ratio =< 1 OR 24-hour urine protein < 500 mg
  • INR =< 1.5 (unless on full-dose warfarin)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for >= 6 months after completion of study treatment
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition to other agents used in the study
  • No serious or nonhealing wound, ulcer, or bone fracture
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • No significant traumatic injury within the past 28 days
  • No clinically significant cardiovascular disease, including any of the following:

    • Myocardial infarction, coronary artery bypass graft, or unstable angina pectoris within the past 6 months
    • New York Heart Association class III or IV congestive heart failure
    • Serious cardiac arrhythmia requiring medication
    • Clinically significant peripheral vascular disease within the past 6 months
    • Cerebrovascular accident within the past 6 months
    • Pulmonary embolism, deep vein thrombosis, or other thromboembolic event within the past 6 months
    • Uncontrolled hypertension, defined as blood pressure (BP) > 150/100 mm Hg or systolic BP > 180 mm Hg (if diastolic BP < 90 mm Hg) within the past 3 months
  • No evidence of bleeding diathesis or coagulopathy
  • No uncontrolled intercurrent illness, including, but not limited to, any of the following:

    • Ongoing or active infection
    • Psychiatric illness or social situation that would preclude study compliance
  • Recovered from prior therapy
  • Prior biologic or targeted therapies allowed
  • No more than 1 prior systemic chemotherapy regimen for metastatic disease
  • No prior antiangiogenic therapy primarily targeting the vascular endothelial growth factor pathway
  • At least 4 weeks since prior radiotherapy or systemic therapy (6 weeks for mitomycin C or nitrosoureas)
  • More than 28 days since prior major surgery or open biopsy
  • More than 7 days since prior core biopsy
  • No concurrent major surgery
  • Concurrent full-dose anticoagulants (e.g., warfarin) allowed provided all of the following criteria are met:

    • In-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or low molecular weight heparin
    • No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
  • No other concurrent investigational agents
  • No concurrent combination antiretroviral therapy for HIV-positive patients

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00407485

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United States, California
City of Hope
Duarte, California, United States, 91010
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Przemyslaw Twardowski City of Hope Medical Center
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Responsible Party: National Cancer Institute (NCI) Identifier: NCT00407485    
Other Study ID Numbers: NCI-2012-02840
NCI-2012-02840 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
PHII-76 ( Other Identifier: City of Hope )
7533 ( Other Identifier: CTEP )
N01CM62201 ( U.S. NIH Grant/Contract )
N01CM62209 ( U.S. NIH Grant/Contract )
First Posted: December 5, 2006    Key Record Dates
Results First Posted: October 3, 2014
Last Update Posted: October 20, 2014
Last Verified: October 2013
Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Urethral Neoplasms
Kidney Neoplasms
Ureteral Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Urethral Diseases
Kidney Diseases
Ureteral Diseases