To Determine the Effect of Food on the Pharmacokinetics of Olaparib and the Effect of Olaparib on QT Interval Following Oral Dosing of a Tablet Formulation in Patients With Advanced Solid Tumours

NCT ID: NCT01921140

Last Updated: 2022-11-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-09-24

Study Completion Date

2022-03-15

Brief Summary

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This is a 3 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 and the effect of olaparib on QT interval following a single oral dose of olaparib tablets. Part B will determine the effect of olaparib on the QT interval following multiple oral dosing. Part C will allow patients continued access to olaparib tablets and will provide additional safety data collection.

Detailed Description

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Conditions

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Solid Tumours

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Fasted

Olaparib tablets following no breakfast

Group Type OTHER

Olaparib tablets

Intervention Type DRUG

Olaparib dosing (2X 150mg tablets) following allocated meal

Pharmacokinetic sampling

Intervention Type PROCEDURE

Blood samples taken pre and post dosing with 2x 150 mg olaparib tablet

Dietary Fasted

Intervention Type OTHER

2x 150 mg olaparib tablet formulation taken in fasted state. 5-14 days washout period

High-fat meal

Olaparib tablets after high-fat breakfast

Group Type OTHER

Olaparib tablets

Intervention Type DRUG

Olaparib dosing (2X 150mg tablets) following allocated meal

Pharmacokinetic sampling

Intervention Type PROCEDURE

Blood samples taken pre and post dosing with 2x 150 mg olaparib tablet

Dietary High Fat

Intervention Type OTHER

2x 150 mg olaparib tablet formulation taken 30 minutes after allocated meal. 5-14 days washout period.

Interventions

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Olaparib tablets

Olaparib dosing (2X 150mg tablets) following allocated meal

Intervention Type DRUG

Pharmacokinetic sampling

Blood samples taken pre and post dosing with 2x 150 mg olaparib tablet

Intervention Type PROCEDURE

Dietary Fasted

2x 150 mg olaparib tablet formulation taken in fasted state. 5-14 days washout period

Intervention Type OTHER

Dietary High Fat

2x 150 mg olaparib tablet formulation taken 30 minutes after allocated meal. 5-14 days washout period.

Intervention Type OTHER

Eligibility Criteria

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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. Able to eat a high-fat meal within a 30-minute period, as provided by the study site.
4. Histologically or, where appropriate, cytologically confirmed malignant solid tumour refractory or resistant to standard therapy or 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 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 5 x ULN.

Serum creatinine less than or equal to 1.5 x institutional ULN. Serum potassium, sodium, magnesium and calcium within the institutional normal range.
6. Calculated serum creatinine clearance greater than 50 mL/min (using Cockroft-Gault formula or by 24-hour urine collection).
7. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2. 8. Patients must have a life expectancy of greater than or equal to 16 weeks.

9\. 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 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 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). 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 (with the exception of electrolyte supplements), 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.

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 (greater than or equal to CTCAE Grade 2) caused by previous cancer therapy, excluding alopecia.
7. 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.
8. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
9. Patients unable to fast for up to 14 hours.
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 computed tomography (HRCT) scan, or any psychiatric disorder that prohibits obtaining informed consent.
11. Patients with a history of poorly controlled hypertension with resting blood pressure (BP) greater than 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.
12. Patients with a history of heart failure or left ventricular dysfunction, and patients who require calcium channel blockers.
13. Patients with type I or type II diabetes.
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 absorption of olaparib.
16. Breastfeeding women.
17. Immunocompromised patients, eg, patients who are known to be serologically positive for human immunodeficiency virus (HIV).
18. Patients with known active hepatic disease (ie, hepatitis B or C).
19. Patients with a known hypersensitivity to olaparib or any of the excipients of the product. 20. Mean QTc with Fridericia's correction (QTcF) greater than 470 ms in screening ECG or history of familial long QT syndrome:

A marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTc interval greater than 470 ms).

A history of additional risk factors for Torsade de pointes (eg, heart failure, hypokalaemia, family history of long QT syndrome).

21\. The use of concomitant medications that prolong the QT/QTc interval. 22. Clinical judgment by the investigator that the patient should not participate in the study
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Anitra Fielding

Role: STUDY_DIRECTOR

AstraZeneca Sponsor Research Physician

Ruth Plummer, Prof

Role: PRINCIPAL_INVESTIGATOR

Northern Centre for Cancer Care, Newcastle Upon Tyne Hospitals

Locations

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Research Site

Brussels, , Belgium

Site Status

Research Site

Leuven, , Belgium

Site Status

Research Site

Liège, , Belgium

Site Status

Research Site

Herlev, , Denmark

Site Status

Research Site

København Ø, , Denmark

Site Status

Research Site

Maastricht, , Netherlands

Site Status

Research Site

Nijmegen, , Netherlands

Site Status

Research Site

Utrecht, , Netherlands

Site Status

Research Site

London, , United Kingdom

Site Status

Research Site

Manchester, , United Kingdom

Site Status

Research Site

Newcastle upon Tyne, , United Kingdom

Site Status

Research Site

Surrey, , United Kingdom

Site Status

Countries

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Belgium Denmark Netherlands United Kingdom

References

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Plummer R, Swaisland H, Leunen K, van Herpen CM, Jerusalem G, De Greve J, Lolkema MP, Soetekouw P, Mau-Sorensen M, Nielsen D, Spicer J, Fielding A, So K, Bannister W, Molife LR. Olaparib tablet formulation: effect of food on the pharmacokinetics after oral dosing in patients with advanced solid tumours. Cancer Chemother Pharmacol. 2015 Oct;76(4):723-9. doi: 10.1007/s00280-015-2836-2. Epub 2015 Aug 5.

Reference Type DERIVED
PMID: 26242220 (View on PubMed)

Related Links

Other Identifiers

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D0816C00004

Identifier Type: -

Identifier Source: org_study_id

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