Overview
This is a phase I, open-label study to assess the safety, tolerability, pharmacokinetics(PK) and anti-tumour activity of adavosertib in Japanese patients with advanced solid tumours. This study consists of 2 cohorts, Cohort1 and Cohort2. At least 3, or up to 6, evaluable Japanese patients with advanced solid tumours will be enrolled in each cohort to confirm the tolerability.
Description
Objectives
Primary objective:
To assess the safety and tolerability, describe any dose-limiting toxicity (DLT) for adavosertib
Secondary objective:
To determine the PK profile of adavosertib To describe adavosertib's preliminary anti-tumour activity using the Response Evaluation Criteria in Solid Tumours (RECIST) v1.1
Overall design:
This is a phase I, open-label study to assess the safety, tolerability, PK and anti-tumour activity of adavosertib in Japanese patients with advanced solid tumours. This study consists of 2 cohorts, Cohort1 and Cohort2. At least 3, or up to 6, evaluable Japanese patients with advanced solid tumours will be enrolled in each cohort. The total number of subjects will depend upon the available data in each cohort and the Safety Review Committee (SRC)'s decision.
Study Period:
The study is expected to start in June 2020 and end in April 2021.
Number of Subjects:
6 to 12 evaluable subjects will be enrolled in this study to confirm the tolerability.
Treatments and treatment duration:
Subjects in each part will receive the study treatments as described below:
Cohort 1: Adavosertib 250 mg by mouth (PO) once daily (QD) for 5 days ON and 2 days OFF for week 1 and 2 of a 21 days cycle Cohort 2: Adavosertib 300 mg PO QD for 5 days ON and 2 days OFF for week 1 and 2 of a 21 days cycle Subjects will be allowed to continue adavosertib until disease progression, intolerable toxicity, or discontinuation criteria have been met.
Eligibility
Major Inclusion Criteria:
- Japanese patients 20 years of age at the time of study entry
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0, 1
- Adequate bone marrow reserve or organ function
- Female patients who are not of child-bearing potential, and fertile females of childbearing potential who agree to use adequate contraceptive measures
- Male patients should be willing to use barrier contraception
- Predicted life expectancy 12 weeks
- Histologically or cytologically documented locally advanced or metastatic solid tumour, excluding lymphoma, for which standard therapy does not exist or has proven ineffective or intolerable
- Measurable or non-measurable disease according to RECIST v1.1
Major Exclusion Criteria:
- Use of anti-cancer treatment drug 21 days or 5 half-lives (whichever is shorter) prior to the first dose of adavosertib
- Use of an investigational drug during the past 30 days or 5 half-lives (whichever is longer) prior to the first dose of the study treatment
- Common Terminology Criteria for Adverse Events (CTCAE) Grade >1 toxicity from prior therapy
- Inability to swallow oral medication or any other condition that may impact adavosertib intake/absorption
- Known malignant central nervous system (CNS) disease other than neurologically stable, treated brain metastases
- Any of the cardiac diseases currently or within the last 6 months
- Any underlying medical condition that would impair the patient's ability to receive study treatment
- Other invasive malignancy within 5 years prior to the first dose of study drug except for non-invasive malignancies