UCL/10/0035

University College London

Joint Research Office, Gower Street, London, United Kingdom, WC1E6BT

public contact, CRUK and UCL Cancer Trials Centre, ctc.sponsor@ucl.ac.uk

Scientific contact, CRUK and UCL Cancer Trials Centre, ctc.sponsor@ucl.ac.uk

No

No

No

Final

19 Nov 2014

No

Yes

26 Feb 2014

Yes

Treatment options for patients with glioblastoma are limited. It accounts for about 60% of brain tumours and life expectancy is limited. Novel treatment options for patients with GBM represents an unmet need. The main objective was to compare the efficacy of cediranib in combination with oral gefitinib with cediranib alone. The primary outcome variable was progression free survival as defined as the date from randomisation to the date of first progression or death due to any cause, whichever one came first.

Patients were closely monitored for side effects while on treatment. Patients were monitored closely for haemorrhagic events and there were clear guidelines in the protocol for the prevention and management of these side effects, including dose adjustment schedules, and daily blood pressure monitoring. Patients also underwent ECGs during the trial. The protocol listed drugs that were not permitted to be used concomitantly with study medication including the need to switch enzyme-inducing anti-epileptic drugs to non-enzyme inducing anti-epileptic drugs.

24 May 2011

No

Yes

United Kingdom: 38

38

38

0

0

0

0

0

0

30

8

0

Overall trial (overall period)

Randomised - controlled

The randomisation schedule that provided details of individual patient treatment were produced by computer software that incorporated a standard procedure for generating random numbers. All study personnel were unaware of the randomised treatment until all decisions regarding the integrity and evaluability of the data from all patients had been made and documented.

Yes

Cediranib

AZD2171

Film-coated tablet

Oral use

Each patient received 30mg od orally. Treatment continued until confirmation of progression, patient decision or the development of unacceptable toxicity. Cediranib was supplied as 35 x film-coated tablets per bottle, containing 30mg cediranib maleate/tablet (20mg and 15mg tablets also available where dose reductions were necessary). Other ingredients are mannitol, dibasic calcium phosphate anhydrous, sodium starch glycolate and magnesium stearate with a film coat containing hypromellose 2910, polyethylene glycol 400, red iron oxide, yellow iron oxide, black iron oxide and titanium dioxide

Gefitinib-matched Placebo

Film-coated tablet

Oral use

Patient received gefitinib-matched placebo, 500mg od orally Drug distributed to patient as 100 x 250mg film-coated tablets identical to Gefitinib per bottle. The tablets contain lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, povidone, sodium lauryl sulphate and magnesium stearate with a film coat containing hypromellose, macrogol 300, red iron oxide, yellow iron oxide and titanium dioxide.

Gefitinib

ZD1839

IRESSA

Film-coated tablet

Oral use

gefitinib 500mg od orally. Gefitinib was distributed to patient as 100 x film-coated tablets per bottle, containing 250mg of gefitinib/tablet. Other ingredients are lactose monohydrate, microcrystalline cellulose (E460), croscarmellose sodium, povidone (K29-32) (E1201), sodium laurilsulfate, magnesium stearate, hypromellose (E464), macrogol 300, titanium dioxide (E171), yellow iron oxide (E172) and red iron oxide (E172).

Cediranib

AZD2171

Film-coated tablet

Oral use

Each patient received 30mg od orally. Treatment continued until confirmation of progression, patient decision or the development of unacceptable toxicity. Cediranib was supplied as 35 x film-coated tablets per bottle, containing 30mg cediranib maleate/tablet (20mg and 15mg tablets also available where dose reductions were necessary). Other ingredients are mannitol, dibasic calcium phosphate anhydrous, sodium starch glycolate and magnesium stearate with a film coat containing hypromellose 2910, polyethylene glycol 400, red iron oxide, yellow iron oxide, black iron oxide and titanium dioxide

Cediranib and Gefitinib-matched Placebo

Cediranib and Gefitinib

Cediranib and Gefitinib-matched Placebo

Cediranib and Gefitinib

Cediranib + Gefitinib: While 19 patients were randomised to this arm, one patient in this arm did not complete their patient diary so it was not possible to confirm that they took any of the randomized medication. Excluding this patient had no material effect on the hazard ratio (0.67, 90% CI 0.38 to 1.18), so they were included in the progression free survival analysis. This patient however was excluded from safety reporting.

Primary

Progression free survival (PFS) defined as the time from the date of randomisation to the date of first progression or death due to any cause, whichever one comes first.

Progression free survival (PFS) defined as the time from the date of randomisation to the date of first progression or death due to any cause, whichever one comes first.

Cediranib and Gefitinib-matched Placebo v Cediranib and Gefitinib

38

Pre-specified

0.72

2-sided

All adverse events that occurred between informed consent and 30 days post last trial treatment administration had to be reported.

SAEs are listed in full. Non-serious adverse events includes all events (including SAEs) of grade 3 or higher with a 5% threshold frequency.

4.03

Cediranib + Gefitinib

Cediranib + Placebo