Cancer: Solid tumour (Malignant solid tumour) Cancer Solid tumour
Conditions
Interventions
Taking Investigational product, itraconazol and QT Interval measurements.
Sponsors
Astra Zeneca
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
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 *18 years 3. Histologically or, where appropriate, cytologically confirmed malignant solid tumour refractory or resistant to standard therapy and 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 - Serum potassium, sodium, magnesium, and calcium within the institutional normal range 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 postmenopausal 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 postmenopausal 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 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
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 (see Section 5.6.1 for guidelines and washout periods) 6. Toxicities ( 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 symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. Patients with asymptomatic brain metastases or with symptomatic but stable brain metastases can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. 9. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery 10. Patients unable to fast for up to 14 hours 11. 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. 12. Patients with a history of poorly controlled hypertension with resting blood pressure (BP) >150/100 mm Hg in the presence or absence of a stable regimen of hypertensive therapy. Measurements will be made after the patient has been resting supine for a minimum of 5 minutes. Two or more readings should be taken at 2-minute intervals and averaged. If the first 2 diastolic readings differ by more than 5 mm Hg, an additional reading should be obtained and averaged. 13. Patients with a history of heart failure, or left ventricular dysfunction, and patients who require calcium channel blockers 14. Patients who have gastric, gastro-oesophageal or oesophageal cancer 15. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders or significant gastrointestinal resection likely to interfere with the absorption olaparib. 16. Breastfeeding women 17. Immunocompromised pat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary objective: To investigate the effect of itraconazole on the PK of olaparib following oral dosing of the tablet formulation in patients with advanced solid tumours Primary outcome variable(s): Maximum plasma olaparib concentration (Cmax) Olaparib area under the plasma concentration time curve from zero to infinity (AUC) (or area under the plasma concentration time curve from zero to the last measurable time point, AUC0-t, if AUC is not adequately estimable) PK pharmacokinetics | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary objectives: To characterise the PK of olaparib following oral dosing of the tablet formulation in the presence and absence of itraconazole To demonstrate exposure to itraconazole and hydroxy-itraconazole To investigate the effect of olaparib on the QT interval corrected for heart rate (QTc) following single (Part A) and multiple (Part B) oral doses of the tablet formulation To investigate further the safety and tolerability of olaparib tablets in patients with advanced solid tumours Secondary outcome variables: Time to reach maximum plasma concentration for olaparib (tmax), Olaparib area under the plasma concentration time curve from zero to the last measurable time point (AUC0-"), Olaparib apparent clearance (CL/F), Olaparib apparent volume of distribution (Vz/F), Olaparib terminal half-life (t1/2) Itraconazole Cmax, AUC0-", tmax, and CL/F; hydroxy-itraconazole Cmax, AUC0-", and tmax ECG intervals (including QT and QTc interval) Assessment of AEs, graded by CTCAE v4.03, physical examination (including BP and pulse), and evaluation of laboratory parameters (clinical chemistry, haematology, and urinalysis) | — |
Countries
Netherlands
Outcome results
None listed