Cancer Solid Tumour
Conditions
Interventions
In Part A, each patient will receive a single 300 mg oral dose of olaparib,
given as the tablet formulation, on Days 1 and 14 after an overnight fast. Each
dose will comprise 2 x 150 mg tablets for
Sponsors
Astra Zeneca
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Provision of written informed consent prior to any study-specific procedures 2. Patients aged *18 years 3. Histologically or, where appropriate, cytologically confirmed malignant solid tumour refractory or resistant to standard therapy or for which no suitable effective standard therapy exists 4. Patients must have normal organ and bone marrow function measured within 28 days prior to administration of investigational product (IP) as defined below: Haemoglobin (Hb) *10.0 g/dL, with no blood transfusions in the previous 28 days - Absolute neutrophil count (ANC) *1.5 x 109/L - White blood cells (WBC) >3 x 109/L- Platelet count *100 x 109/L- Total bilirubin *1.5 x institutional upper limit of normal (ULN) (except in the case of Gilbert*s disease)- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) *2.5 x institutional ULN unless liver metastases are present, in which case it must be *5x ULN - Serum creatinine *1.5 x institutional ULN 5. Calculated serum creatinine clearance >50 mL/min (using Cockroft-Gault formula or by 24 hour urine collection) 6. Eastern Cooperative Oncology Group (ECOG) performance status *2 7. Patients must have a life expectancy of *16 weeks. 8. Evidence of non-childbearing status for women of childbearing potential, or post menopausal status: negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on Day 1 of Part A. Post-menopausal is defined as:- Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments- Luteinising hormone and follicle stimulating hormone levels in the post menopausal range for women under 50 years of age- Radiation-induced oophorectomy with last menses >1 year ago- Chemotherapy-induced menopause with >1 year interval since last menses- Surgical sterilisation (bilateral oophorectomy or hysterectomy) 9. Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations. 10. Patients must be on a stable concomitant medication regimen (with the exceptionof electrolyte supplements), defined as no changes in medication or in dose within the 2 weeks prior to start of olaparib dosing, except for bisphosphonates, denosumab, and corticosteroids, which should be at a stable dose for at least 4 weeks prior to the start of olaparib dosing.
Exclusion criteria
Exclusion criteria: 1. Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff, its agents, and/or staff at the study site) 2. Previous enrolment in the present study 3. 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) 4. 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). The patient can receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study, as long as these were started at least 4 weeks prior to treatment. 5. Patients who have received or are receiving inhibitors or inducers of CYP3A4 6. Toxicities (*Common Toxicity Criteria for Adverse Events [CTCAE] Grade 2) caused by previous cancer therapy, excluding alopecia 7. 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 the IP until the end of Part A 8. Patients with brain metastases. A scan to confirm the absence of brain metastases is not required. 9. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of major surgery 10. Patients considered a poor medical risk due to a serious uncontrolled medical disorder, non malignant systemic disease, uncontrolled seizures, or active uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive bilateral interstitial lung disease on high resolution computer tomography (HRCT) scan, or any psychiatric disorder that prohibits obtaining informed consent. 11. Patients who have diabetes mellitus 12. Patients who have gastric, gastro-oesophageal, or oesophageal cancer 13. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders or significant gastrointestinal resection likely to interfere with the absorption of olaparib 14. Breastfeeding women 15. Immunocompromised patients, eg, patients who are known to be serologically positive for human immunodeficiency virus (HIV) 16. Patients with known active hepatic disease (eg, hepatitis B or C) 17. Patients with a known hypersensitivity to rifampicin or any of the excipients of the product 18. Patients with a known hypersensitivity to olaparib or any of the excipients of the product 19. Resting electrocardiogram (ECG) at screening with measurable QT interval (QT) corrected for heart rate (QTc) >470 msec at 2 or more time points within a 24 hour period or family history of long QT syndrome 20. Concomitant medication contraindicated for use with rifampicin (including, but not limited to): atazanavir, darunavir, fosamprenavir, ritonavir-boosted saquinavir, saquinavir, or tipranavir 21. Patients who receive a seasonal flu vaccine (including H1N1, H1N5) must defer enrolment for 28 days post-vaccination. 22. Patients who have jaundice 23. Patients who weigh <50 kg 24. Clinical judgment by the investigator that the patient should not participate in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics In Part A, the following variables will be calculated for olaparib where the data allow: maximum plasma concentration (Cmax), time to reach maximum plasma concentration (tmax), area under the plasma concentration-time curve from zero to the last measurable time point (AUC0-t), area under the plasma concentration-time curve from zero to infinity (AUC), apparent plasma clearance following oral administration (CL/F), apparent volume of distribution (Vz/F), terminal rate constant (*z), and terminal half-life (t1/2). Pharmacokinetics will not be measured in Part B. | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety Assessment of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v4.0, physical examination, vital signs (including blood pressure, pulse), standard 12-lead electrocardiogram (ECG), and evaluation of laboratory parameters (clinical chemistry, haematology, and urinalysis). | — |
Countries
Netherlands
Outcome results
None listed