A Phase I, Open-Label, Multicentre Study to Compare Two Dosage Formulations of AZD5363 and to Establish the Effect of Food on the Pharmacokinetic Exposure, Safety and Tolerability of AZD5363 in Patients with Advanced Solid Malignancies (OAK)

For many types of cancer there is an urgent need for new treatments. AZD5363 is
a new anti cancer treatment that inhibits the kinase activity of AKT. AZD5363
acts on cancers by blocking signalling throught the AKT cellular survival
pathway, leading to inhibition of cell proliferation and increased apoptosis.
AZD5363 has not yet been administerd to humans. The main purpose of this study
is to investigate the safety and tolerability of AZD5363 in patients with
advanced solid malignancies. The switch from AZD5363 capsules to tablets is
explored, as well as the effect of food on AZD5363. The information gathered
from this study is important for the further development of this substance and
the treatment of future subjects with this substance.

Part A: to compare the PK exposure of a new AZD5363 tablet formulation with
that of the AZD5363 capsule formulation in patients with advanced solid
malignancies.

Part B: to explore the effect of a standardised meal on the PK exposure of a
new tablet formulation of AZD5363 in patients with advanced solid malignancies.

Phase I, open-label, multi-centre study.

Twice daily dosing with AZD5363 following an intermittent schedule.

Intermittent schedule:
* the patient is dosed 4 days on, 3 days off AZD5263 treatment.
* depending on emerging data the intermittent '2 days on/ 5 days off AZD5363
treatment' may be explored..

Part A:
The starting dose is 480 mg AZD5363 twice daily in the '4 on/ 3 off'
intermittent schedule. During the first week the patient is dosed with the new
AZD5363 tablet formulation, as of the second week the patient is dosed with the
capsule formulation.
* depending on emerging data other strenghts and schedules may be explored.
* if the tablet formulation is comparable to the tablet formulation, it may be
allowed to replace the capsules by tablets.

Deel B:
The starting dose is the recommended dose established in part A.

On several days during the study patients will undergo the following
assessments: physical examination, vital signs, ECG, MUGA/echocardiogram, blood
and urine testing, tumour sample (optional), CT scan, MRI or X ray, collection
of hairfollicles, pregnancy tests.

During the study female patients should avoid to become pregnant and male
patients should avoid to father a child.

AZD5363 can cause side effects. The following side effects are known from
previous clinical research with AZD5363:
- High sugar level
- Diarrhoea
- Rash

Known from laboratory research:
- Changes in the strenght of the heart beat and blood pressure.
- Changes in liver function.
- Changes in pituitary, thyroid and adrenal glands as well as in the
reproductive tract.






Vrouwelijke patiënten mogen tijdens de behandeling niet zwanger raken en
mannelijke patiënten mogen geen kinderen verwekken.