A091962

Cambridge University Hospitals NHS Foundation Trust & University of Cambridge

Addenbrooke’s Hospital, Hills Road, Cambridge, United Kingdom, CB2 0QQ

Chief Investigator, Cambridge University Hospitals NHS Foundation Trust , cctu.cancer@addenbrookes.nhs.uk

Chief Investigator, Cambridge University Hospitals NHS Foundation Trust , cctu.cancer@addenbrookes.nhs.uk

No

No

No

Final

17 Sep 2015

Yes

25 Sep 2014

Yes

25 Sep 2014

No

What causes high blood pressure in some patients taking pazopanib as a treatment for cancer?

The study was approved by a Research Ethics Committee and received authorisation from the Medicines and Healthcare Products Regulatory Authority. Patients received verbal and written information prior to consenting to the trial and had the time to consider their participation and opportunity to ask questions. Consenting patients had a series of screening tests and exams to ensure they were suitable for the study and that it was safe to proceed. The patients were monitored in the clinic every 2 weeks up to 12 weeks for assessment and monitoring of safety including ECG, Vital signs, blood/ urine tests. A visit at 3 weeks of treatment was added partway through the trial to monitor liver function. CT scans were performed at 12 weekly intervals to monitor disease status. After 12 weeks, patients who continued treatment were then monitored every 4 weeks up to 6 months, then every 3 months Treatment was stopped or dose reduced on the development of treatment toxicities. Patients received pazopanib therapy until death, loss of clinical benefit, unacceptable toxicity or withdrawal from the study for any other reason. Patients attended a follow-up visit 28 days after stopping pazopanib therapy for safety and disease status assessments. On registration to the trial, the patients were allocated a unique reference number to be used on all data and samples sent to the Sponsor which allowed their personal data to remain anonymous. Only the patients' direct care team had access to their recruited participants personal data during the study. Patients were allowed to withdraw their consent to the study at any time.

23 Jun 2011

No

Yes

United Kingdom: 27

27

27

0

0

0

0

0

0

18

9

0

Baseline

Not applicable

Pazopanib

GW786034

Votrient

Film-coated tablet

Oral use

800 mg once daily

Hypertension Visit

Not applicable

Yes

Pazopanib

GW786034

Votrient

Film-coated tablet

Oral use

800 mg once daily

Pazopanib

GW786034

Votrient

Film-coated tablet

Oral use

800 mg once daily

Baseline

All Patients

Hypertensive Group

Non Hypertensive

Safety Population

All patients who receive at least one dose of pazopanib will be included in the safety population.

Research Population

All patients who complete visit V2, or V8/VHyp (as applicable) will be included in the research population. This population will be used in evaluation of the primary and secondary endpoints.

Change in forearm blood flow ratio (of infused vs control arm) in response to intra-arterial acetycholine infusion. There is a hierarchy of observations: Patient, Visits (baseline and Hyp), Dose (Saline or active Challenge Dose), forearm (control or infused), and replications of individual forearm blood flow observations (3-4). Aggregate endpoints for each patient are calculated that are the ratio of ratios of geometric means of individual Infused:Control forearm ratios: (Challenge / Saline at Visit Hyp)/ (Challenge/ Saline at Baseline ).

Primary

measured at initial baseline visit, and subsequent visit where a patient was classified as either hyper-tensive or non-hyper-tensive according to blood pressure measurements.

A mixed effect model was used to predict the log-transformed infused:control forearm blood flow ratio values as a function of Visit, Dose, Hypertensive status. Random effect intercepts were fitted at the patient and patient-visit level. They key estimate for the scientific interpretation is the interaction between (Visit Hyp – Visit baseline ):( High Dose – Base Dose):(Hypertension – non-Hypertension), which corresponds to the study objectives.

Hypertensive Group v Non Hypertensive

13

Pre-specified

-0.0854

2-sided

Standard error of the mean

0.189

Adverse events were collected from screening through to the follow-up visit, 28 days post last dose of pazopanib.

Adverse events were assessed at each clinic visit throughout the study by a clinician. A document listing the individual Adverse Events, and providing a frequency table broken down by AE category, grade, relatedness, and seriousness, is uploaded separately.

3

All Patients