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Tivozanib Before Surgery in Treating Patients With Localized Kidney Cancer

Primary Purpose

Stage II Renal Cell Cancer, Stage III Renal Cell Cancer

Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
tivozanib
therapeutic conventional surgery
Sponsored by
Roswell Park Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage II Renal Cell Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Biopsy proven non-metastatic clear cell RCC, as per radiographic studies is T2 - T3a based on the American Joint Committee on Cancer (AJCC) 6th edition criteria
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
  • Hemoglobin >= 10 gm/dL
  • Absolute neutrophil count (ANC) >= 1.5 X 10^9/L
  • Platelets >= 100 X 10^9/L
  • Total bilirubin < 1.5 X upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 X ULN
  • International normalization ratio (INR) < 1.5
  • Activated partial thromboplastin time (aPTT) < 1.2 X ULN
  • Serum creatinine < 1.5 mg/dL or if >= 1.5 mg/dL: calculated creatinine clearance (CrCL) > 30 mL/min based on Cockroft-Gault formula
  • Must have the ability to swallow and retain oral medication
  • Patients of childbearing potential must agree to use acceptable contraceptive methods (e.g., double barrier) during treatment
  • Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

  • Pregnant or nursing female patients
  • Unwilling or unable to follow protocol requirements
  • Any condition which in the Investigator's opinion deems the patient an unsuitable candidate to receive tivozanib (solitary kidney, multiple tumors in the same or contralateral kidney)
  • Not a candidate for surgery
  • Received an investigational agent within 30 days prior to enrollment
  • Non-clear cell or sarcomatoid histology
  • Patients with metastatic disease at presentation
  • Prior therapy with tyrosine kinase inhibitor for RCC
  • A second primary malignancy (except squamous and basal cell carcinoma of skin) in the past 3 years
  • Active or chronic infections

  • Significant cardiovascular disease, including:

    • Clinically symptomatic left ventricular failure
    • Uncontrolled hypertension: systolic blood pressure of > 150 mmHg or diastolic blood pressure of > 100 mmHg documented on 2 consecutive measurements taken at least 24 hours apart
    • Myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of tivozanib
    • History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation)
    • Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)
    • Coronary or peripheral artery bypass graft within 6 months of screening
  • History of coronary artery disease or peripheral arterial disease
  • History of stroke or carotid endarterectomy
  • Patients who are taking cytochrome P450 system (CYP)3A4 inducers are excluded; patients taking CYP3A4 inducers that can be safely replaced with another agent may be enrolled after a 5 day washout period

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Treatment (tivozanib and surgery)

    Arm Description

    Patients receive tivozanib PO QD on days 1-21. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. 25 days after completion of tivozanib, patients undergo curative nephrectomy.

    Outcomes

    Primary Outcome Measures

    Feasibility of conducting a trial of tivozanib in terms of patients completing 2 courses of tivozanib

    Secondary Outcome Measures

    Short-term efficacy defined as a composite of presence of partial response/stable disease/complete response assessed radiographically and correlated with the nephrectomy specimen per the Response Evaluation Criteria in Solid Tumors (RECIST) criteria
    Response rate will be examined using the sample proportion and corresponding 95% confidence interval.
    Incidence of adverse events evaluated using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Full Information

    First Posted
    January 15, 2013
    Last Updated
    August 11, 2022
    Sponsor
    Roswell Park Cancer Institute
    Collaborators
    AVEO Pharmaceuticals, Inc.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01769885
    Brief Title
    Tivozanib Before Surgery in Treating Patients With Localized Kidney Cancer
    Official Title
    A Pilot Clinical Trial of Neoadjuvant Tivozanib in Localized Renal Cell Carcinoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2022
    Overall Recruitment Status
    Withdrawn
    Study Start Date
    March 14, 2013 (Actual)
    Primary Completion Date
    June 14, 2013 (Actual)
    Study Completion Date
    December 2, 2013 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Roswell Park Cancer Institute
    Collaborators
    AVEO Pharmaceuticals, Inc.

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This clinical trial studies tivozanib before surgery in treating patients with localized kidney cancer. Tivozanib may stop the growth of tumor cells by blocking some of the growth factors needed for cell growth.
    Detailed Description
    PRIMARY OBJECTIVES: I. To assess the feasibility of conducting a trial of tivozanib in the neoadjuvant setting of localized (completely resectable) renal cell cancer (RCC). SECONDARY OBJECTIVES: I. To evaluate the safety of tivozanib in the neoadjuvant setting. II. To compare the tissue before and after tivozanib for pharmacodynamic purposes (tumor infiltrating lymphocytes, myeloid derived suppressor cells, necrosis in the primary tumor after exposure to tivozanib). III. To assess the overall response rate of tivozanib in primary tumors and correlate the radiographic changes, if any, to histo-pathological changes in the pathology specimen post-nephrectomy. IV. To compare the various growth factors (vascular endothelial growth factor [VEGF], interleukin-8 [IL-8], placenta growth factor [P1GF]) at baseline and post treatment. V. To assess the nephrectomy rate after applying neoadjuvant tivozanib in this primarily resectable RCC population. OUTLINE: Patients receive tivozanib orally (PO) once daily (QD) on days 1-21. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. 25 days after completion of tivozanib, patients undergo curative nephrectomy. After completion of study treatment, patients are followed up at 30 days.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Stage II Renal Cell Cancer, Stage III Renal Cell Cancer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Treatment (tivozanib and surgery)
    Arm Type
    Experimental
    Arm Description
    Patients receive tivozanib PO QD on days 1-21. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. 25 days after completion of tivozanib, patients undergo curative nephrectomy.
    Intervention Type
    Drug
    Intervention Name(s)
    tivozanib
    Other Intervention Name(s)
    AV-951, oral VEGF receptor tyrosine kinase inhibitor AV-951
    Intervention Description
    Given PO
    Intervention Type
    Procedure
    Intervention Name(s)
    therapeutic conventional surgery
    Intervention Description
    Undergo nephrectomy
    Primary Outcome Measure Information:
    Title
    Feasibility of conducting a trial of tivozanib in terms of patients completing 2 courses of tivozanib
    Time Frame
    Up to 30 days after surgery
    Secondary Outcome Measure Information:
    Title
    Short-term efficacy defined as a composite of presence of partial response/stable disease/complete response assessed radiographically and correlated with the nephrectomy specimen per the Response Evaluation Criteria in Solid Tumors (RECIST) criteria
    Description
    Response rate will be examined using the sample proportion and corresponding 95% confidence interval.
    Time Frame
    Up to 30 days after surgery
    Title
    Incidence of adverse events evaluated using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
    Time Frame
    Up to 30 days after surgery

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Biopsy proven non-metastatic clear cell RCC, as per radiographic studies is T2 - T3a based on the American Joint Committee on Cancer (AJCC) 6th edition criteria Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 Hemoglobin >= 10 gm/dL Absolute neutrophil count (ANC) >= 1.5 X 10^9/L Platelets >= 100 X 10^9/L Total bilirubin < 1.5 X upper limit of normal (ULN) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 X ULN International normalization ratio (INR) < 1.5 Activated partial thromboplastin time (aPTT) < 1.2 X ULN Serum creatinine < 1.5 mg/dL or if >= 1.5 mg/dL: calculated creatinine clearance (CrCL) > 30 mL/min based on Cockroft-Gault formula Must have the ability to swallow and retain oral medication Patients of childbearing potential must agree to use acceptable contraceptive methods (e.g., double barrier) during treatment Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: Pregnant or nursing female patients Unwilling or unable to follow protocol requirements Any condition which in the Investigator's opinion deems the patient an unsuitable candidate to receive tivozanib (solitary kidney, multiple tumors in the same or contralateral kidney) Not a candidate for surgery Received an investigational agent within 30 days prior to enrollment Non-clear cell or sarcomatoid histology Patients with metastatic disease at presentation Prior therapy with tyrosine kinase inhibitor for RCC A second primary malignancy (except squamous and basal cell carcinoma of skin) in the past 3 years Active or chronic infections Significant cardiovascular disease, including: Clinically symptomatic left ventricular failure Uncontrolled hypertension: systolic blood pressure of > 150 mmHg or diastolic blood pressure of > 100 mmHg documented on 2 consecutive measurements taken at least 24 hours apart Myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of tivozanib History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication) Coronary or peripheral artery bypass graft within 6 months of screening History of coronary artery disease or peripheral arterial disease History of stroke or carotid endarterectomy Patients who are taking cytochrome P450 system (CYP)3A4 inducers are excluded; patients taking CYP3A4 inducers that can be safely replaced with another agent may be enrolled after a 5 day washout period
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Saby George
    Organizational Affiliation
    Roswell Park Cancer Institute
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

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    Tivozanib Before Surgery in Treating Patients With Localized Kidney Cancer

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