Solid Tumours
Conditions
Keywords
oncology, cancer, tumour, neoplasm, anticancer drug, food effect, area under the curve, pharmacokinetics, olaparib, solid tumour, metabolites, drug availability
Brief summary
This is a 2 part study for patients with solid tumours. The purpose of Part A is to measure the amount of olaparib or its breakdown products in the bloodstream for up to 72 hours after eating 3 different breakfasts (high calorie, regular and none). In Part B Patients can take olaparib capsules daily and study assessments will be recorded for 6 months (minimum). Treatment can continue for as long as the patient is benefitting. Throughout the study patients will be monitored for any side effects.
Interventions
DRUGOlaparib
400mg olaparib capsule formulation taken 30 minutes after allocated meal. 5-14 days between arms.
OTHERDietary Fasted
Allocated breakfast prior to dosing with 400mg olaparib capsules
OTHERDietary standard
Allocated breakfast prior to dosing with 400mg olaparib capsules
OTHERDietary High Fat
Allocated breakfast prior to dosing with 400mg olaparib capsules
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Patients aged ≥18 years, male and female * Able to eat a high-fat breakfast within a 30-minute period, as provided by the study site * Histologically or, where appropriate, cytologically confirmed malignant solid tumour refractory or resistant to standard therapy and for which no suitable effective standard therapy exists * ECOG performance status ≤2 * Normal organ and bone marrow function measured within 28 days prior to administration of IP as defined in protocol
Exclusion criteria
* Participation in another clinical study with an IP during the last 14 days (or a longer period depending on the defined characteristics of the agents used) * Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 2 weeks prior to study treatment (or a longer period depending on the defined characteristics of the agents used). * Toxicities (≥CTCAE Grade 2) caused by previous cancer therapy, excluding alopecia * Patients unable to fast for up to 14 hours or who have type I or type II diabetes * Patients who have gastric, gastro-oesophageal or oesophageal cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of Olaparib (Cmax and tmax) | Blood samples will be collected in each of the 3 treatment periods in Part A at these time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72hours post dose | Rate and extent of absorption of olaparib following single-dose olaparib by assessment of maximum plasma olaparib concentration (Cmax) and time to reach maximum plasma concentration (tmax) |
| Pharmacokinetics of Olaparib (AUC0-t) | Blood samples will be collected in each of the 3 treatment periods in Part A at these time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72hours post dose. | Rate and extent of absorption of olaparib following single-dose olaparib by assessment of area under the plasma concentration time curve from zero to the last measurable time point (AUC0-t) |
| Pharmacokinetics of Olaparib (AUC) | Blood samples will be collected in each of the 3 treatment periods in Part A at these time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72hours post dose | Rate and extent of absorption of olaparib following single-dose olaparib by assessment of area under the plasma concentration time curve from zero to infinity (AUC) |
| Pharmacokinetics of Olaparib Pharmacokinetics of Olaparib (CL/F, Vz/F, λz and t½) | Blood samples will be collected in each of the 3 treatment periods in Part A at these time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72hours post dose. | Rate and extent of absorption of olaparib following single-dose olaparib by assessment of apparent clearance following oral administration (CL/F), apparent volume of distribution (Vz/F), terminal rate constant (λz), and terminal half-life (t½) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety monitoring of Olaparib | AEs will be collected from signed informed consent up to 30-day post last dose in Part A. For patients in Part B, AE's will be collected until the final patient has completed 6 months in Part B, including 30 day follow up for those who discontinue | Assessment of adverse events (AEs), graded by CTCAE (v4.0), physical examination, vital signs (including BP and pulse), standard 12-lead ECG and evaluation of laboratory parameters (clinical chemistry, haematology, and urinalysis). Assessment of physical examination, vital signs, ECG and evaluation of laboratory parameters will occur at screening, on the day before dosing in each treatment period and 30 days after last dose. |
Countries
Belgium, Netherlands, United Kingdom
Outcome results
None listed