A Randomised, Open-label, Phase I Study to Determine the Effect of Food on the pharmacokinetics of AZD1775 After Oral Dosing of a Capsule Formulation in Patients with Advanced Solid Tumours.

1. Read and understand the informed consent form (ICF) and given written informed
consent prior to any study procedures.
2. Histologically or cytologically documented, locally advanced or metastatic solid
tumour, excluding lymphoma, for which standard therapy does not exist or has
proven ineffective or intolerable.
3. Any prior palliative radiation must have been completed at least 7 days prior to the
start of study treatment, and patients must have recovered from any acute adverse
effects prior to the start of study treatment.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of
0 to 1.
5. Baseline laboratory values within 7 days of study treatment initiation:
* Absolute neutrophil count (ANC) *1500/*L.
* Haemoglobin *9 g/dL.
* Platelets *100,000/*L.
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
*3 x upper limit of normal (ULN) or *5 x ULN if known hepatic metastases.
* Serum bilirubin within normal limits (WNL) or *1.5 x ULN in patients with
liver metastases; or total bilirubin *3.0 x ULN with direct bilirubin WNL in
patients with well documented Gilbert*s Syndrome.
* Serum creatinine *1.5 x ULN, or measured creatinine clearance (CrCl)
calculated by Cockcroft-Gault method *45 mL/min (confirmation of creatinine
clearance is only required when creatinine is >1.5 x ULN)
(CrCl (glomerular filtration rate) <= (140-age) x (weight/kg) x Fa) /
(72 x serum creatinine mg/dL) -where F <= 0.85 for females and F <= 1 for males
6. Female patients who are not of childbearing potential and fertile females of
childbearing potential who agree to use adequate contraceptive measures that are in
during screening (or consent), for the duration of the study, and for 1 month after
treatment stops, and who are not breastfeeding, and who have a negative serum or
urine pregnancy test prior to the start of study treatment.
7. Male patients should be willing to use barrier contraception (ie, condoms) for the
duration of the study and for 3 months after study treatment discontinuation.
8. Female or male patients *18 years.
9. Patient should be able to adequately consume a high-fat meal as prescribed in
Treatment B.
10. Willingness and ability to comply with the study and the follow-up procedures.

1. Involvement in the planning and/or conduct of the study (applies to both
AstraZeneca personnel and/or personnel at the study centre).
2. Previous enrolment or randomisation and received study treatment in the present
study. Patients can, however, be re-screened if the reason for the screen failure no
longer exists.
3. Known malignant central nervous system (CNS) disease other than neurologically
stable, treated brain metastases * defined as metastasis having no evidence of
progression or haemorrhage for at least 2 weeks after treatment (including brain
radiotherapy). Must be off any systemic corticosteroids for the treatment of brain
metastases for at least 14 days prior to enrolment.
4. Use of any anti-cancer treatment drug *21 days or 5 half-lives (whichever is
shorter) prior to the first administration of AZD1775. For drugs for which
5 half-lives is *21 days, a minimum of 10 days between termination of the prior
treatment and administration of AZD1775 treatment is required.
5. No other anticancer-therapy (chemotherapy, immunotherapy, hormonal anti-cancer
therapy, radiotherapy [except for palliative local radiotherapy]), biological therapy
or other novel agent is to be permitted while patient is receiving study treatment.
Patients on LHRH analogue treatment for more than 6 months are allowed entry
into the study and may continue at the discretion of the Investigator.
6. Patients suffering from conditions which are likely to adversely affect
gastrointestinal motility and/or transit (for example, diarrhoea, vomiting or nausea,
gastroparesis, irritable bowel syndrome and malabsorption) or patients with
gastrointestinal resection (eg, partial or total gastrectomy) likely to interfere with
absorption of study treatment.
7. Major surgical procedures *28 days of beginning study treatment, or minor surgical
procedures *7 days. No waiting period required following port-a-cath placement or
other central venous access placement.
8. Grade >1 toxicities from prior therapy, according to the Common Terminology
Criteria for Adverse Events (CTCAE), excluding alopecia or anorexia.
9. Patient has an inability to swallow oral medications. Note: Patient may not have a
percutaneous endoscopic gastrostomy tube or be receiving total parenteral nutrition.
10. Patients who are not non-smokers or light smokers (no more than 5 cigarettes per
day) and who cannot abstain from smoking from 2 weeks prior to the first
administration of AZD1775 until after the last PK sample collection in Period 2.
11. Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange
marmalade, or other products containing grapefruit or Seville oranges within 7 days
of the first administration of AZD1775.
12. Patient has had prescription or non-prescription drugs or other products known to be
sensitive to cytochrome P450 (CYP)3A4 substrates or CYP3A4 substrates with a
narrow therapeutic index, or to be moderate to strong inhibitors/inducers of
CYP3A4 which cannot be discontinued 2 weeks prior to Day 1 of dosing and
withheld throughout the study until 2 weeks after the last administration of
AZD1775. Co-administration of aprepitant or fosaprepitant during this study is
prohibited.
13. Patient has had adjustments to prescription or non-prescription drugs or other
products known to be weak inhibitors and/or inducers of CYP3A4 within 1 week
prior to the first administration of AZD1775.
14. Herbal preparations taken within 7 days of study entry. However, in the case of
St John*s wort, patients cannot have taken this herbal preparation 21 days prior to
first administration of AZD1775.
15. Patients who have taken any proton pump inhibitors (omeprazole, lansoprazole,
esomeprazole, pantoprazole, etc) within 7 days of first administration of AZD1775.
16. Patients who are dependent on a medication which could adversely affect
gastrointestinal motility or transit (for example: diphenoxylate, [loperamide],
metoclopramide, cisapride, tegaserod, erythromycin). Note that use of loperamide
is permitted during the study for treatment of diarrhoea.
17. Patients who cannot withhold antacids for 6 hours or H2-antagonists (cimetidine,
ranitidine, famotidine, nizatidine) for 48 hours.
18. Patients unable to fast for up to 14 hours.
19. Patients with type 1 diabetes mellitus.
20. Any known hypersensitivity or contraindication to AZD1775 or to the components
thereof.
21. Any of the following cardiac diseases currently or within the last 6 months as
defined by the New York Heart Association * Class 2.
* Unstable angina pectoris.
* Congestive heart failure.
* Acute myocardial infarction.
* Conduction abnormality not controlled with pacemaker or medication.
* Significant ventricular or supraventricular arrhythmias (patients with chronic
rate-controlled atrial fibrillation in the absence of other cardiac abnormalities
are eligible).
22. AZD1775 should not be given to patients who have a history of Torsades de pointes
unless all risk factors that contributed to Torsades have been corrected. AZD1775
has not been studied in patients with ventricular arrhythmias or recent myocardial
infarction.
23. Patients with QT interval (specifically QTc calculated using the Fridericia formula
[QTcF] >450 ms/male and >470 ms/female) obtained from 3 electrocardiograms
(ECGs) 2 to 5 minutes apart at study entry, or congenital long QT syndrome.
24. Pregnant or lactating female patients.
25. Serious, symptomatic active infection at the time of study entry, or another serious
underlying medical condition that would impair the ability of the patient to receive
study treatment.
26. Active infection with hepatitis B, hepatitis C, or human immunodeficiency virus
(HIV).;Any of the following is regarded as a criterion for exclusion from the optional
pharmacogenetic part of the study:
27. Previous bone marrow transplant.
28. Non-leukocyte depleted blood product within 120 days of the genetic sample
collection.