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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00407485
First received: December 4, 2006
Last updated: October 10, 2014
Last verified: October 2013
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Tumor Response Rate [ Time Frame: From the start of the treatment until disease progression or recurrence, assessed up to 4 years ] [ Designated as safety issue: No ]

    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.


  • Progression-free Survival (PFS) [ Time Frame: From start of treatment to time of progression, assessed up to 4 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 22
Study Start Date: November 2006
Study Completion Date: April 2014
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

PRIMARY OBJECTIVES:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00407485

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
Sponsors and Collaborators
Investigators
Principal Investigator: Przemyslaw Twardowski Beckman Research Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00407485     History of Changes
Other Study ID Numbers: NCI-2012-02840, NCI-2012-02840, PHII-76, 7533, N01CM62201, N01CM62209
Study First Received: December 4, 2006
Results First Received: August 27, 2014
Last Updated: October 10, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Carcinoma, Squamous Cell
Carcinoma, Transitional Cell
Kidney Neoplasms
Ureteral Neoplasms
Urethral Neoplasms
Urinary Bladder Neoplasms
Kidney Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Ureteral Diseases
Urethral Diseases
Urinary Bladder Diseases
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms

ClinicalTrials.gov processed this record on November 27, 2014