Investigators will test the value of very low dose Pazopanib administered to patients with hereditary hemorrhagic telangiectasia for the reduction in the severity of nose bleeds in those with frequent and long duration bleeding episodes.
Based on frequency and nose bleed duration, a non-randomized, single arm, open label study of 30 hereditary hemorrhagic telangiectasia patients will be treated with very low dose Pazopanib \[25mg-similar\] for between 16 and 24 weeks.. The primary endpoint is a reduction in bleeding duration of 50% or more, along with multiple secondary related endpoints, including bleed frequency, blood counts and quality of life; as compared to 6-12 weeks of baseline characteristics. If after the first 8 weeks of therapy benefit is suboptimal, dose advance to 50mg-similar daily can be considered.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Active pharmaceutical ingredient plus excipients filled into a capsule for the lower dosing necessary in this study
Percent change in epistaxis duration in minutes
A daily electronic record of each bleed, with start and end time, provides the daily epistaxis duration, compounded over each 3 weeks of study time
Time frame: Summed minutes of bleeding at baseline 3 weeks and the last 3 weeks of dosing, over16-24 weeks of dosing
Percent change in average gushing frequency
Patient rated intensity of each bleed, as in 0 or 1, averaged over 3 wk periods.
Time frame: Last 3 weeks of drug period vs baseline 3 weeks; over 16-24 weeks of dosing
Percent change in average bleed frequency
Annotated number of bleeds per day, and summed over 3 week periods
Time frame: Last 3 weeks compared to the baseline 3 weeks; over 16-24 weeks of dosing
Absolute [gm/dl] change in serum hemoglobin
Serum values drawn every 3 weeks
Time frame: comparing last 6 weeks to baseline 3-6 weeks; over 16-24 weeks of drug dosing
Change in the frequency of blood transfusions
Use of packed red blood cells over 6 week time periods.
Time frame: Final 6 weeks of study, compared to baseline 3-6 weeks; over 16- 24 weeks of dosing
Change in the frequency of IV iron infusions
Number of interval IV iron infusions in 6 week periods
Time frame: Last 6 weeks of dosing to first 6 weeks; over 16-24 weeks of drug administration
Percent change in the per bleed average epistaxis severity
Epistaxis severity score \[0-10\] housed in the current patient reported outcome instrument will be averaged
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Time frame: The final 3 weeks to the baseline 3 weeks of the study; for a16-24 week duration study
Daily monitoring for change in systolic blood pressure [mm mercury] using daily recordings
Patients rising above 140 mm mercury, or those who increase by 20 or more mm mercury will trigger protocol defined treatments.
Time frame: Daily from baseline through up to 24 weeks till on-drug study completion.
Daily monitoring for change in diastolic blood pressure [mm mercury]
Patients rising above 90 mm mercury, or those who increase by 10 mm mercury or more will trigger protocol defined treatments.
Time frame: Daily from baseline through up to 24 weeks till on-drug study completion
Number of participants with changes in alanine aminotransferase [liver function test]
measurement every 3 weeks to evaluate fold increase with use of drug
Time frame: Baseline and throughout the 16-24 week dosing period
Monitor for active and safe trough serum drug concentrations
Assays to be analyzed to evaluate the exposures done to remain within safe and effective range \[1ug/ ml to 10ug/ml\].....
Time frame: Over 16-24 week duration of study; once at steady state for each administered dose
Evaluate for change in composite mental quality of life scores
short form health survey 36 \[range 1-100, higher number representing better self-reported mental health\]
Time frame: baseline, week 12 and at study drug-dosing end; 16, 20 or 24weeks
Evaluate for change in composite physical quality of life scores
short form health survey 36 \[range 1-100, higher number representing better self-reported physical health\]
Time frame: baseline, week 12 and at study drug-dosing end; up to 24 weeks.
Evaluate for change in fatigue composite scores
Patient-report outcome measurement information system-fatigue; \[0-100 scale; lower number representing less fatigue\]. Queries the degree of fatigue and the implications on physical functioning. Reduction of 5 or more in the composite score represents clinically relevant reductions in fatigue.
Time frame: baseline and study end; up to 24 weeks