A Phase II Study of Tivozanib in Patients With Metastatic and Non-resectable Soft Tissue Sarcomas
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|ClinicalTrials.gov Identifier: NCT01782313|
Recruitment Status : Completed
First Posted : February 1, 2013
Results First Posted : August 21, 2018
Last Update Posted : September 18, 2018
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Adult Soft Tissue Sarcoma Stage III Adult Soft Tissue Sarcoma Stage IV Adult Soft Tissue Sarcoma||Drug: tivozanib Other: laboratory biomarker analysis||Phase 2|
I. To determine the progression-free survival (defined as complete response [CR] + partial response [PR] + stable disease [SD]) assessed at 16 weeks for patients treated with tivozanib.
I. Overall response rate (defined as CR + PR). II. Clinical benefit rate (CR + PR + SD). III. Overall survival (up to 2 years beyond progression). IV. Correlation of clinical outcome with antibodies for vascular endothelial growth factor receptor 1 (VEGFR1) and VEGFR2.
V. Assess Safety and tolerability.
Patients receive tivozanib orally (PO) daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity, or until discontinuation per patient preference or physician recommendation.
After completion of study treatment, patients are followed up every 3 months for 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||58 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Tivozanib in Patients With Metastatic and Non-resectable Soft Tissue Sarcomas|
|Actual Study Start Date :||March 6, 2013|
|Actual Primary Completion Date :||July 27, 2015|
|Actual Study Completion Date :||December 28, 2016|
Experimental: Treatment (tivozanib)
Patients receive tivozanib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: laboratory biomarker analysis
- Percentage of Patients With Progression-free Survival at 16 Weeks. [ Time Frame: At 16 weeks of treatment. ]
Progression-free survival from study disease will be evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) Committee, version 1.1 assessed using imaging scans (CT or MRI) and clinical assessment following 16 weeks of treatment.
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", or similar definition as accurate and appropriate.
- Overall Response Rate Defined as Complete Response and Partial Response. [ Time Frame: Every 2 cycles (8 weeks) up to 2 years ]
The response to study treatment will be assessed after every 8 weeks (2 cycles) of therapy using CT or MRI scan images.Overall response rate will be measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI:
Complete response (CR) = disappearance of all target lesions. Partial Response (PR), = at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
- Clinical Benefit Rate as Defined by Complete Response, Partial Response and Stable Disease. [ Time Frame: Every 2 cycles (8 weeks) up to 2 years ]
The clinical benefit of study treatment will be assessed after 8 weeks (2 cycles) of therapy using scanning images (CT or MRI). Clinical benefit rate will be measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI:
Complete Response (CR) = disappearance of all target lesions. Partial Response (PR), = at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Progressive Disease (PD) = At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
- Overall Survival up to 2 Years Beyond Progression [ Time Frame: Time from the first dose of study treatment up to 2 years beyond disease progression ]Patients will be followed-up with from first dose of study drug up to 2 years following the date of disease progression.
- Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment [ Time Frame: Tissue collected during screening process, prior to first treatment and response measured until 350 days. ]
Tissue from biopsy will be collected during screening and proteins (VEGFR1 and VEGFR2) will be evaluated to see if there is a correlation with patient response to treatment.
VERGFR = vascular endothelial growth factor receptor
To determine if there was a correlation between response to Tivozanib and VEGFR expression, immunohistochemical (IHC) analysis on archival tumor tissue was performed. We performed standard IHC and applied combined intensity score (from 0 to 3) for antigen expression and proportional score of 0-3 for the cells that were positive. For antigen expression, 0 was no staining, +1 being 1-25% staining, +2 being 26-50% staining and +3 being 50% or greater staining. Number of patients with VEGFR1 expression was correlated with time patients were on treatment in days.
- Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment. [ Time Frame: After every 4 weeks (1 cycle) until treatment discontinuation and up to a maximum of 2 years and 10 months. ]
Toxicity will be assessed after 4 weeks (1 cycle) and every 4 weeks during treatment according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 4.0 (CTCAE v4.0). In general adverse events (AEs) will be graded according to the following:
Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE
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 ClinicalTrials.gov identifier (NCT number): NCT01782313
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|United States, Iowa|
|University of Iowa|
|Iowa City, Iowa, United States, 52246|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, Missouri|
|Saint Louis, Missouri, United States, 63110|
|United States, Wisconsin|
|University of Wisconsin|
|Madison, Wisconsin, United States, 53792|
|Principal Investigator:||Mark Agulnik, MD||Northwestern University|