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

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

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.

Study Overview

• Status: Completed
• Conditions: Cancer; Advanced Solid Malignancies
• Intervention / Treatment: Drug: olaparib

Detailed Description

MTD - maximum tolerated dose

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chuo-ku, Japan, 104-0045
    • Research Site
  • Fukuoka-shi, Japan, 811-1395
    • Research Site
  • Sapporo-shi, Japan, 003-0804
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: olaparib tablet monotherapy; olaparib tablet	Drug: olaparib; tablet oral

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Thomas Morris, M.D., Global Medicines Development

Publications and helpful links

Helpful Links

• D081BC00001_Study_Report_Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2013
• Primary Completion (Actual): August 31, 2016
• Study Completion (Actual): August 31, 2016

Study Registration Dates

• First Submitted: March 15, 2013
• First Submitted That Met QC Criteria: March 18, 2013
• First Posted (Estimate): March 19, 2013

Study Record Updates

• Last Update Posted (Actual): January 16, 2018
• Last Update Submitted That Met QC Criteria: December 15, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Cancer; Tumour; Solid Malignancies
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Olaparib
• Other Study ID Numbers: D081BC00001