Study to Assess the Effect of Rifampicin (CYP Inducer) on Blood Levels and Safety of Olaparib in Patients With Advanced Solid Tumours

Inclusion Criteria:- For inclusion in the study, patients should fulfil the following criteria: 1. Provision of written informed consent prior to any study-specific procedures. 2. Patients aged greater than or equal to 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) greater than or equal to 10.0 g/dL, with no blood transfusions in the previous 28 days. Absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L. White blood cells (WBC) greater than 3 x 109/L. Platelet count greater than or equal to 100 x 109/L. Total bilirubin less than or equal to 1.5 x institutional upper limit of normal (ULN) (except in the case of Gilbert's disease). Aspartate aminotransferase (AST), alanine aminotransferase (ALT) less than or equal to 2.5 x institutional ULN unless liver metastases are present, in which case it must be less than or equal to 5x ULN, Serum creatinine less than or equal to 1.5 x institutional ULN. 5\. Calculated serum creatinine clearance greater than 50 mL/min (using Cockroft-Gault formula or by 24 hour urine collection). 6\. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2. 7\. Patients must have a life expectancy of greater than or equal to 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 greater than 1 year ago. Chemotherapy-induced menopause with greater than 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 exception of 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:- Patients should not enter the study if any of the following exclusion criteria are fulfilled. 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 (greater than or equal to 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) greater than 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 have jaundice. 22. Patients who weigh less than 50 kg. 23. Clinical judgment by the investigator that the patient should not participate in the study.