Investigate the Safety and Tolerability of Olaparib Tablet in Japanese Patients With Advanced Solid Malignancies

Study Overview
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Brief Summary
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The objective of this study will be to investigate the safety and tolerability of olaparib tablet when given orally to Japanese patients with advanced solid malignancies. In addition, the pharmacokinetic profile, MTD (if possible) and efficacy of olaparib will be investigated.

Detailed Description
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MTD - maximum tolerated dose

Official Title
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A Phase I, Open-label Study to Assess the Safety and Tolerability of Doses of Olaparib Tablet in Japanese Patients With Advanced Solid Malignancies

Conditions
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Cancer, Advanced Solid Malignancies

Intervention / Treatment
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* Drug: olaparib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects diagnosed with advanced solid malignancies who are refractory to standard therapies or for which no standard therapy exists. Subjects who have overall good overall general condition. Subjects who agree to hospitalisation from starting olaparib to multiple dose period at day 15. Evidence of non-childbearing status for women of childbearing potential, or postmenopausal status. Subjects who have at least one lesion (measurable and/or non-measurable) that can be accurately assessed by CT/MRI at baseline and follow up visits Exclusion Criteria: Subjects who received any previous treatment with a PARP (poly adenosine diphosphate-ribose polymerase) inhibitor, including olaparib. Subjects receiving inhibitors of CYP3A4 (cytochrome P450 3A4). Subjects with symptomatic uncontrolled brain metastases. Subjects with myelodysplastic syndrome/acute myeloid leukaemia. Subjects with a known hypersensitivity to olaparib or any of the excipients of the product.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: olaparib tablet monotherapy<br>olaparib tablet | Drug: olaparib<br>* tablet oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | An adverse event is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. This was recorded if it happend from the start dose to 30 days after the last of study drug. | From the start dose to 30 days after the last dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose Limiting Toxicities | Dose Limiting Toxicities were defined as study specific events that is determined to be possibly or probably related to olaparib (as determined by the investigator) and occurring during the first cycle of treatment (28 days after the first dose), irrespective of whether the toxicity resolved. | From the start dose to 28 days after the first dose of study drug | 
| Cmax Following Single Dosing |  | Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours at post-dose | 
| Cmax Following Multiple Dosing |  | Day 15: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours at post-dose | 
| Tmax Following Single Dosing |  | Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours at post-dose | 
| Tmax Following Multiple Dosing |  | Day 15: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours at post-dose | 
| AUC Following Single Dosing |  | Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours at post-dose | 
| AUC at Steady State Following Multiple Dosing |  | Day 15: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours at post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Tumour, Solid Malignancies