Cancer Solid Tumour
Conditions
Interventions
During Period 1, prior to administration of the first dose of study treatment,
each patient will be randomised to 1 of 2 treatment sequences to receive a
single oral dose of 300 mg AZD1775 in each o
Advanced solid Tumours
Food effect
Sponsors
Astra Zeneca
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 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)
Exclusion criteria
Exclusion criteria: 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 inhib
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum plasma concentration (Cmax), area under the plasma concentration-time curve from zero to infinity (AUC), and area under the plasma concentration time curve from zero to the last quantifiable time point (AUC0-t) of AZD 1775 | — |
Secondary
| Measure | Time frame |
|---|---|
| Time to reach maximum plasma concentration (tmax), terminal half-life (t*), terminal rate constant (*z), apparent plasma clearance (CL/F) and apparent volume of distribution (Vz/F) of AZD1775 Safety and Tolerability of AZD1775: Assessment of adverse events, graded by CTCAE (v4.03), physical examination, vital signs (blood pressure, pulse rate and body temperature), 12-lead electrocardiogram, and evaluation of laboratory parameters (clinical chemistry and haematology) | — |
Countries
France, Netherlands, United Kingdom
Outcome results
None listed