Solid Tumours
Conditions
Keywords
Pharmacokinetics, WEE1 inhibitor, food effect, safety assessments
Brief summary
The purpose of this study is to assess the effect of food on the pharmacokinetics (PK) of a single dose of AZD1775 (printed capsules) in patients with advanced solid tumours.
Detailed description
This is a Phase I, open-label, randomised, 2-period crossover design study in patients with advanced solid tumours. The purpose of this study is to assess the effect of food on the pharmacokinetics (PK) of a single dose of AZD1775 (printed capsules).In addition single dose safety and tolerability data will be gathered. Patients will be screened within 28 days of Day 1 of the first treatment period (Period 1). Patients will take part in 2 randomised treatment sequences each separated by a washout period of at least 5 and no more than 14 days. During Period 1, prior to administration of the first dose of study treatment, each patient will be randomised to 1 of 2 treatment sequences (Fasted-Fed or Fed-Fasted) to receive a single oral dose of 300 mg AZD1775 in each of the 2 treatment periods as follows: * Fasted (Treatment A): Single dose 300 mg AZD1775, (3 x 100 mg, printed capsules). * Fed (Treatment B): Single dose 300 mg AZD1775, (3 x 100 mg, printed capsules). Pharmacokinetic and safety assessments will be obtained for up to 72 hours post-dose in each treatment period. On completion of the study (ie, after collection of 72-hour PK sample and safety in period 2) patients will be evaluated per current assessments for their eligibility and interest to enrol into the open-label continued treatment access study (D6014C000007).
Interventions
DRUGTreatment A - AZD1775 administered under fasted conditions
Premedication with Kytril (granisetron) 1 mg intravenously or Zofran (ondansetron) 8 mg intravenously within 30 to 40 minutes prior to administration of the AZD1775 capsules. Single dose 300 mg AZD1775, (3 x 100 mg, printed capsules) administered orally under fasted conditions. The drug class of AZD1775 is Wee-1 kinase inhibitor.
DRUGTreatment B - AZD1775 administered under fed conditions.
Premedication with Kytril (granisetron) 1 mg intravenously or Zofran (ondansetron) 8 mg intravenously within 30 to 40 minutes prior to administration of the AZD1775 capsules. Single dose 300 mg AZD1775, (3 x 100 mg, printed capsules) administered orally under fed conditions. The drug class of AZD1775 is Wee-1 kinase inhibitor.
Sponsors
Quintiles, Inc.
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
For inclusion in the study patients should fulfil the following criteria: * Read and understand the informed consent form (ICF) and given written informed consent prior to any study procedures. * 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. * 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. * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to 1. * Baseline laboratory values within 7 days of study treatment initiation: * Absolute neutrophil count (ANC) ≥1500/μL. * Haemoglobin ≥9 g/dL. * Platelets ≥100,000/μL. * 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 * 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. * 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 * Female or male patients ≥18 years. * Patient should be able to adequately consume a high-fat meal as prescribed in Treatment B. * Willingness and ability to comply with the study and the follow-up procedures. * For inclusion in the optional genetic component of the study for all the patients: * Provision of informed consent for genetic research. If a patient declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in the CSP, as long as all the eligibility criteria are met.
Exclusion criteria
Patients should not enter the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the plasma concentration-time curve from zero to infinity for AZD1775 | Blood samples are collected on Day 1 of each treatment period at pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours post AZD1775 dose | To investigate the effect of food on the PK of a single dose of AZD1775 printed capsules following oral dosing in patients with advanced solid tumours |
| Area under the plasma concentration-time curve from time zero to the time t (AUC0-t) of the last quantifiable concentration for AZD1775 | Blood samples are collected on Day 1 of each treatment period at pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours post AZD1775 dose | To investigate the effect of food on the PK of a single dose of AZD1775 printed capsules following oral dosing in patients with advanced solid tumours |
| Cmax: maximum plasma drug concentration for AZD1775 | Blood samples are collected on Day 1 of each treatment period at pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours post AZD1775 dose | To investigate the effect of food on the PK of a single dose of AZD1775 printed capsules following oral dosing in patients with advanced solid tumours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| t½,: terminal half-life for AZD1775 | Blood samples are collected on Day 1 of each treatment period at pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours post AZD1775 dose | To characterise the PK of a single dose of AZD1775 printed capsules following oral dosing in patients with advanced solid tumours |
| Apparent volume of distribution for AZD1775 | Blood samples are collected on Day 1 of each treatment period at pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours post AZD1775 dose | To characterise the PK of a single dose of AZD1775 printed capsules following oral dosing in patients with advanced solid tumours |
| Adverse Events, graded by the National Cancer Institute Common Terminology Criteria for Adverse Event's (CTCAE v4.3) | Until 30 days following the final dose of AZD1775 | To assess the safety and tolerability of a single dose of AZD1775 printed capsules following oral dosing in patients with advanced solid tumours. |
| Complete physical examination including performance status assessed using the Eastern Cooperative Oncology Group (ECOG) Performance Status criteria. | Until 30 days following the final dose of AZD1775 | To assess the safety and tolerability of a single dose of AZD1775 printed capsules following oral dosing in patients with advanced solid tumours. If new or aggravated physical findings imply deterioration compared with baseline, the finding will be reported as an Adverse Event. |
| Pulse Rate (beats/min) | Until 30 days following the final dose of AZD1775 | To assess the safety and tolerability of a single dose of AZD1775 printed capsules following oral dosing in patients with advanced solid tumours. |
| tmax,: time to reach maximum plasma concentration for AZD1775 | Blood samples are collected on Day 1 of each treatment period at pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours post AZD1775 dose | To characterise the PK of a single dose of AZD1775 printed capsules following oral dosing in patients with advanced solid tumours |
| Electrocardiogram (ECG) - A 12-lead safety ECG (paper ECG printout of 10 seconds for Investigator review) | Until 7 days following the final dose of AZD1775 | To assess the safety and tolerability of a single dose of AZD1775 printed capsules following oral dosing in patients with advanced solid tumours. The Investigator will judge the overall interpretation as normal or abnormal. If abnormal, it will be decided as to whether or not the abnormality is clinically significant or not clinically significant. |
| Blood Pressure (mm Hg) | Until 30 days following the final dose of AZD1775 | To assess the safety and tolerability of a single dose of AZD1775 printed capsules following oral dosing in patients with advanced solid tumours. |
| Body Temperature (°C) | Until 30 days following the final dose of AZD1775 | To assess the safety and tolerability of a single dose of AZD1775 printed capsules following oral dosing in patients with advanced solid tumours. |
| Evaluation of Clinical Chemistry Parameters (Albumin, Alanine Transaminase, Aspartate Transaminase, Alkaline Phosphatase, Bilirubin, Calcium, Creatinine, Glucose, Total protein, Chloride, Potassium, Sodium, Urea nitrogen) | Until 30 days following the final dose of AZD1775 | Laboratory tests will be performed by an accredited laboratory. Deterioration of clinical chemistry values as compared to baseline will be reported as Adverse Events if they fulfil any of the Serious Adverse Events criteria or are the reason for discontinuation of the study treatment unless clearly due to the progression of disease under study. If deterioration in a laboratory value is associated with clinical signs and symptoms, the sign or symptom will be reported as an AE and the associated laboratory result will be considered as additional information. |
| Evaluation of Haematology Parameters (Haemoglobin, Leukocyte and Leukocyte counts, Red blood cell count, Haematocrit and Platelet Count) | Until 30 days following the final dose of AZD1775 | Laboratory tests will be performed by an accredited laboratory. Deterioration of haematology laboratory values as compared to baseline will be reported as Adverse Events if they fulfill any of the Serious Adverse Events criteria or are the reason for discontinuation of the study treatment unless clearly due to the progression of disease under study. If deterioration in a laboratory value is associated with clinical signs and symptoms, the sign or symptom will be reported as an AE and the associated laboratory result will be considered as additional information. |
| λz: Elimination rate constant for AZD1775 | Blood samples are collected on Day 1 of each treatment period at pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours post AZD1775 dose | To characterise the PK of a single dose of AZD1775 printed capsules following oral dosing in patients with advanced solid tumours |
| Apparent clearance following oral administration for AZD1775 | Blood samples are collected on Day 1 of each treatment period at pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours post AZD1775 dose | To characterise the PK of a single dose of AZD1775 printed capsules following oral dosing in patients with advanced solid tumours |
Countries
France, Netherlands, United Kingdom
Outcome results
None listed