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Tivozanib for Recurrent Glioblastoma

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.
 
ClinicalTrials.gov Identifier: NCT01846871
Recruitment Status : Completed
First Posted : May 3, 2013
Results First Posted : January 8, 2019
Last Update Posted : January 8, 2019
Sponsor:
Collaborator:
National Comprehensive Cancer Network
Information provided by (Responsible Party):
Elizabeth R. Gerstner, MD, Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE May 1, 2013
First Posted Date  ICMJE May 3, 2013
Results First Submitted Date  ICMJE December 17, 2018
Results First Posted Date  ICMJE January 8, 2019
Last Update Posted Date January 8, 2019
Study Start Date  ICMJE June 2013
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 17, 2018)
Number of Patients Alive and Progression Free After 6 Months [ Time Frame: 6 months ]
To determine the number of patients with recurrent glioblastoma (GBM) alive and progression free 6 months (PFR6) after start of tivozanib therapy
Original Primary Outcome Measures  ICMJE
 (submitted: May 1, 2013)
Determine proportion of patients alive and progression free after 6 months [ Time Frame: 6 months ]
To determine the proportion of patients with recurrent glioblastoma (GBM) alive and progression free 6 months (PFR6) after start of tivozanib therapy
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 17, 2018)
  • Number of Participants With Treatment Related Serious Adverse Events [ Time Frame: From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months ]
    The number of participants with serious adverse events deemed possibly, probably, or definitely related to treatment. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 4).
  • Median Overall Survival [ Time Frame: From the start of treatment until the time of death, median duration of approximately 8 months ]
    Overall survival is measured from the start of treatment until the time of death.
  • Median Progression-Free Survival [ Time Frame: From the start of treatment until death or progression, median duration of approximately 2 months ]
    Progression free survival is measured as the amount of time from the start of treatment until the time of death or disease progression. Progressive disease was assessed using MacDonald Criteria Progressive disease: Progressive neurologic abnormalities not explained by causes unrelated to tumor 40 progression (example: anti-epileptic drug or corticosteroid toxicity, electrolyte abnormalities, hyperglycemia, etc.) or a greater than 25% increase in the volume of the tumor by MRI scan. If neurologic status deteriorates on a stable or increasing dose of corticosteroids, or if new lesions appear on serial MRI scans, this will also be considered PD.
  • Best RANO Criteria Response [ Time Frame: 2 years ]
    Best response as assessed by Response Assessment in Neuro-Oncology (RANO) criteria. Complete response
    • disappearance of all enhancing disease
    • sustained for at least 4 weeks
    • stable/improved non-enhancing FLAIR/T2W lesions
    • no new lesions
    • no corticosteroids
    • clinically stable/improved
    Partial response >50% or more decrease of all measurable enhancing lesions
    • sustained for at least 4 weeks
    • no progression of non-measurable disease
    • stable/improved non-enhancing FLAIR/T2W lesions
    • no new lesions
    • stable/reduced corticosteroids
    • clinically stable/improved
    Stable disease
    • does not qualify for complete response, partial response or progression
    • stable non-enhancing FLAIR/T2W lesions
    • stable or reduced corticosteroids
    • clinically stable
    Progression >25% or more increase in enhancing lesions despite stable/increasing steroid dose
    • increase in non-enhancing FLAIR/T2W lesions, not attributable to other non-tumor causes
    • any new lesion
    • Clinical deterioration
  • Steroid Dosage [ Time Frame: 2 years ]
    The number of participants on steroids at baseline and the number of participants that increased or decreased their use of steroids during the course of treatment. Participants that required an increase and decrease in steroid use over the course of treatment were counted in both categories.
  • Change in Tumor Volume [ Time Frame: Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks) ]
    Change in volume of the tumor in cubic centimeters at the given time points as compared to baseline
  • Median Apparent Diffusion Coefficient (ADC) [ Time Frame: Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks) ]
    Change in the the median ADC value from baseline at the given timepoints. Apparent diffusion coefficient (ADC) is a measure of the magnitude of diffusion (of water molecules) within tissue.
  • Median Ktrans [ Time Frame: Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks) ]
    Change in the the median Ktrans value from baseline at the given time points. The volume transfer constant (Ktrans) reflects the efflux rate of gadolinium contrast from blood plasma into the tissue extravascular extracellular space (EES)
  • Relative Oxygen Saturation [ Time Frame: Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks) ]
    The change in relative O2 saturation from baseline to the given time points. Oxygen saturation is a relative measure of the concentration of oxygen that is dissolved or carried in a given medium as a proportion of the maximal concentration that can be dissolved in that medium.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 1, 2013)
  • Determine safety of tivozanib [ Time Frame: 2 years ]
    To determine the safety of tivozanib in this patient population
  • Determine progression free and overall survival [ Time Frame: 2 years ]
    To determine the progression free and overall survival of patients with recurrent GBM treated with tivozanib
  • Determine radiographic response using standard CE cranial MRI [ Time Frame: 2 years ]
    To determine radiographic response using standard contrast-enhanced cranial MRI techniques
  • Assess the steroid dose/duration before, during and after treatment [ Time Frame: 2 years ]
    To assess the steroid dose/duration before, during and after treatment with tivozanib
  • Assess the correlation of treatment outcome to specific serial circulating cytokines/receptors [ Time Frame: 2 years ]
    Assess the correlation of treatment outcome to specific serial circulating cytokines/receptors and cell populations to determine whether these markers can be predictive of response to tivozanib (exploratory)
  • Assess effect of tivozanib on GBM tumor growth [ Time Frame: 2 years ]
    Assess the effect of tivozanib on GBM tumor growth by using physiologic MRI parameters of perfusion, permeability, oxygenation status, diffusion, kurtosis and functional connectivity and resting-state networks
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tivozanib for Recurrent Glioblastoma
Official Title  ICMJE A Phase II Study of Tivozanib in Recurrent Glioblastoma
Brief Summary

This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the study drug tivozanib is still being studied. It also means that the FDA has not yet approved tivozanib for your type of cancer.

Tivozanib is an anti-angiogenesis medicine that fights different types of cancer by blocking the blood supply to the tumor, so that the tumor does not receive the nutrients it requires to grow.

In this research study, we are looking to see what effects, good and bad, tivozanib will have on you and your disease.

Detailed Description

If you are willing to participate in this study, you will be asked to undergo some screening tests and procedures that confirm you are eligible. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out taht you do not take part in the research study. If you have had some of these tests or procedures recently, they may or may not have to be repeated. The screening process may include the following: a medical history, mini-mental status exam, physical exam, performance status, electrocardiogram, blood tests, urine test. If these tests show that you are eligible to participate in the research study, you will begin the study treatment. If you do not meet the eligibility criteria, you will not be able to participate in this research study.

If you take part in this research study, you will be given a study drug-dosing calendar for each treatment cycle. Each treatment cycle lasts 28 days (4 weeks) during which time you will be taking the study drug once daily for 3 weeks and then no study drug for the last week of each cycle. The diary will also include special instructions for taking the study drug.

During all cycles you will have a physical exam and you will be asked questions about your general health and specific questions about any problems that you might be having and any medications you may be taking.

Standard contrast-enhanced (CE) MRI scans will be done prior to all odd-numbered study cycles. Vascular MRI scans will be done prior to start of treatment, Day 1 of treatment and prior to all even-numbered cycles. These studies will be done in the Charlestown Navy Yard.

We would like to keep track of your medical condition for up to 24 months after your last dose of study treatment. We would like to do this by calling you on the telephone once a year to see how you are doing. Keeping in touch with you and checking your condition every year helps us look at the long-term effects of the research study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma
Intervention  ICMJE Drug: Tivozanib
Other Name: AV-951
Study Arms  ICMJE Experimental: Tivozanib
1.5 mg daily for 3 weeks, with 1 week off.
Intervention: Drug: Tivozanib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 1, 2016)
10
Original Estimated Enrollment  ICMJE
 (submitted: May 1, 2013)
21
Actual Study Completion Date  ICMJE May 2016
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed glioblastoma that has progressed based on imaging or surgery
  • Measurable disease
  • No more than 3 prior chemotherapy regimens
  • Must have recovered from toxicity of prior therapy. An interval of at least 3 months must have elapsed since the completion of the most recent course of radiotherapy; at least 3 weeks since last non-nitrosourea containing chemotherapy regimen or molecularly targeted agent; at least 6 weeks since the completion of a nitrosourea containing chemotherapy regimen
  • Life expectancy of at least 12 weeks
  • Able to tolerate MRIs
  • Willing to use adequate, highly effective contraception measures while on study and for at least 45 days after the last dose of study drug

Exclusion Criteria:

  • Pregnant or breastfeeding
  • Major surgical procedure or significant traumatic injury within 28 days of starting therapy; or minor surgical procedure within 7 days
  • Receiving other study agents
  • Prior therapy with an anti-VEGF agent
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to tivozanib
  • Receiving any medications or substances that are inhibitors or inducers of CYP450 enzymes
  • Significant cardiovascular disease
  • Non-healing wound, bone fracture or skin ulcer
  • Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis or other gastrointestinal condition with increased risk of perforation; abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug
  • Uncontrolled intercurrent illness
  • Significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug
  • Significant bleeding disorders within 6 months prior to administration of first dose of study drug
  • Currently active second primary malignancy
  • HIV positive and on combination antiretroviral therapy
  • Inability to swallow capsules, malabsorption syndrome or gastrointestinal disease that severely affects the absorption of study drugs, major resection of the stomach or small bowel, or gastric bypass procedure
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01846871
Other Study ID Numbers  ICMJE 13-069
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Elizabeth R. Gerstner, MD, Massachusetts General Hospital
Study Sponsor  ICMJE Massachusetts General Hospital
Collaborators  ICMJE National Comprehensive Cancer Network
Investigators  ICMJE
Principal Investigator: Elizabeth Gerstner, MD Massachusetts General Hospital
PRS Account Massachusetts General Hospital
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP