COSAKV1

Common Services Agency

South Gyle Crescent, Edinburgh, United Kingdom, EH12 9EB

Dr Joanna Dunlop, Scottish Clinical Trials Research Unit, 0131 275 7178, joanna.dunlop@nhs.net

Professor Thomas Powles, St Bartholomew's Hospital, thomas.powles@bartshealth.nhs.uk

No

No

No

Final

15 May 2015

Yes

17 Jan 2014

Yes

12 Dec 2014

No

The primary research objective is to see whether patients taking cediranib in combination with saracatanib have a longer progression free survival (surviving without their cancer returning or relapsing) than the patients who are taking cediranib with placebo.

Laboratory tests were performed at baseline and throughout the study including measurement of serum chemistry and haematology values (sodium, potassium, urea, creatinine, bilirubin, AST and/or ALT, alkaline phosphatase, LDH, albumin, total protein, calcium, phosphate, Hb, WCC, ANC, platelets and TSH). Any clinically significant laboratory abnormalities were recorded as adverse events. Patients were assessed by the investigator to determine if the abnormal finding was sufficient to immediately withdraw the patients from the study. Any laboratory value that met the definition of Serious Adverse Event must be reported as an SAE. In addition, the patient was reassessed for continuation in the study and any indicated and appropriate therapies should be initiated. In addition to the laboratory test, blood pressure was regularly monitored throughout the trial to identify treatment related hypertension, a hypertension management protocol for emergency hypertension was put in place. Data was reviewed 6 months after the first patient entered the study by the DMC, who assess the data primarily from the stand-point of safety and treatment deliverability.

02 Sep 2010

No

Yes

United Kingdom: 138

138

138

0

0

0

0

0

0

91

47

0

Baseline (overall period)

Randomised - controlled

At each site only the investigator and trial pharmacist have access to this system to unblind the patient. In an emergency if these two individuals are unavailable a 24 hour helpline was available. In this case it would be the Chief Investigator who would advise if unblinding could go ahead. Treatment codes are only broken in medical emergencies when appropriate management of the patient necessitates knowledge of the treatment randomisation.

Yes

Saracatinib

Tablet

Oral use

175mg once daily

Cediranib

Tablet

Oral use

30mg od

Cediranib and Saracatinib

Cediranib and placebo

Primary

Patients were randomised to receive study drug until progression of disease, death, excess toxicity or discontinuation for another reason. Radiological assessment (RECIST v1.1) occurred eight weekly until progression.

A Kaplan-Meier plot of progression free survival was presented. The median progression free survival time for each study arm was tabulated together with the corresponding 80% confidence interval. The corresponding hazard ratio and 80% confidence interval and 1-sided p-value associated with the comparison of the treatment arms from the Cox model fitted to the data was reported. This is the primary comparison.

Cediranib and Saracatinib v Cediranib and placebo

138

Pre-specified

1.179

1-sided

Standard error of the mean

0.177

Any time between start of first treatment and within 30 days after administration of last dose of study drug.

All laboratory values were coded according to the CTC toxicity criteria and the worst value over the study drug periods was determined for each patient. All adverse events were similarly coded. NOTE that this study uses a 10% reporting threshold although this system would only allow a max value of 5%.

3.0

Cediranib and Saracatinib

Cediranib and placebo