A Two-part, Randomised, Open-label, Multicentre, Phase I Study to Determine the Effect of Food on the Pharmacokinetics of Olaparib Following Single 400 mg Doses of the Capsule Formulation in Patients with Advanced Solid Tumours
- Conditions
- Cancer: Solid tumour (Malignant solid tumour)CancerSolid tumour
- Registration Number
- NL-OMON40586
- Lead Sponsor
- Astra Zeneca
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 15
For inclusion in the study patients must fulfil the following criteria:
1. Provision of written informed consent prior to any study specific procedures
2. Patients must be >18 years of age.
3. Able to eat a high fat meal within a 30 minute period, as provided by the site.
4. Histologically or, where appropriate, cytologically confirmed malignant solid tumour refractory or resistant to standard therapy and for which no suitable effective standard therapy exists.
5. Normal organ and bone marrow function measured within 28 days prior to administration of investigational product (IP) as defined below:
* Haemoglobin >=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 or serum glutamic oxaloacetic transaminase (AST), alanine aminotransferase or serum glutamic pyruvic transaminase (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
6. Calculated serum creatinine clearance >50 mL/min (using Cockroft-Gault formula or by 24-hour urine collection).
7. Eastern Cooperative Oncology Group (ECOG) performance status <=2.
8. Patients must have a life expectancy >=16 weeks.
9. 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 the first treatment period in Part A.
Postmenopausal 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).
10. Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
11. Patients must be on a stable concomitant medication regimen, defined as no changes in medication or in dose within 2 weeks prior to start of olaparib dosing, except for bisphosphonates, denosumab and corticosteroids, which should be stable for at least 4 weeks prior to start of olaparib dosing.
Patients must 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 both AstraZeneca staff, its agents and/or staff at the study site).
2. Previous enrolment in the present study.
3. Treatment with any investigational product (IP) during the last 14 days (or a longer period depending on the defined characteristics of the agents used).
4. Any previous treatment with a PARP inhibitor, including olaparib.
5. Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for >=5 years.
6. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 2 weeks prior to study treatment. 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.
7. Patients who have received or are receiving inhibitors or inducers of CYP3A4
8. Toxicities (>=CTCAE Grade 2) caused by previous cancer therapy, excluding alopecia.
9. 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.
10. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
11. Patients unable to fast for up to 14 hours.
12. 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.
13. Patients with a history of heart failure or left ventricular dysfunction.
14. Patients with type I or type II diabetes.
15. Patients who have gastric, gastro-oesophageal or oesophageal cancer.
16. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the olaparib, and patients who have had previous gastrointestinal resection.
17. Breastfeeding women.
18. Immunocompromised patients, eg, patients who are known to be serologically positive for human immunodeficiency virus (HIV).
19. Patients with known active hepatic disease (ie, hepatitis B or C).
20. Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
21. Resting ECG with measurable QTc >470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
22. Patients who receive a seasonal flu vaccine (including H1N1, H1
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Pharmacokinetics<br /><br>In Part A, the following variables will be calculated for olaparib where the<br /><br>data allow: maximum plasma concentration (Cmax), time to reach maximum plasma<br /><br>concentration (tmax), area under the plasma concentration time curve from zero<br /><br>to the last measurable time point (AUC0-t), area under the plasma concentration<br /><br>time curve from zero to infinity (AUC), apparent clearance following oral<br /><br>administration (CL/F), apparent volume of distribution (Vz/F), terminal rate<br /><br>constant (*z), and terminal half-life (t*). Other parameters may be determined<br /><br>if deemed appropriate.<br /><br>PK will not be measured in Part B.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Safety<br /><br>Assessment of adverse events (AEs) graded by Common Terminology Criteria for<br /><br>Adverse Events (CTCAE) v4.0, standard 12 lead electrocardiograms (ECGs),<br /><br>physical examination, vital signs (including blood pressure, pulse), and<br /><br>evaluation of laboratory parameters (clinical chemistry, haematology, and<br /><br>urinalysis).</p><br>