Description:
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.
Title
- Brief Title: Study of Adavosertib(AZD1775) in Japanese Patients With Advanced Solid Tumours
- Official Title: A Phase I, Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-Tumour Activity of Adavosertib (AZD1775) in Japanese Patients With Advanced Solid Tumours
Clinical Trial IDs
- ORG STUDY ID:
D601HC00008
- NCT ID:
NCT04462952
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Adavosertib (AZD1775) | | Adavosertib monotherapy |
Purpose
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.
Detailed 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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Adavosertib monotherapy | Experimental | Dose escalation of adavosertib monotherapy for patients with advanced solid tumours | |
Eligibility Criteria
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
| Maximum Eligible Age: | 120 Years |
| Minimum Eligible Age: | 20 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Incidence of Adverse events |
| Time Frame: | From the informed consent to 30 days post last dose |
| Safety Issue: | |
| Description: | Investigate the safety and tolerability of adavosertib |
Secondary Outcome Measures
| Measure: | Maximum plasma drug concentration observed (Cmax) |
| Time Frame: | Samples will be collected on Cycle 1 Day 1,5 and Cycle 2 Day 5, Cycle 3 Day 5 and Cycle 5 Day 5 (each cycle is 21 days). |
| Safety Issue: | |
| Description: | PK parameters will be derived using standard, non-compartmental methods |
| Measure: | Time of maximum plasma drug concentration observed (tmax) |
| Time Frame: | Samples will be collected on Cycle 1 Day 1,5 and Cycle 2 Day 5, Cycle 3 Day 5 and Cycle 5 Day 5 (each cycle is 21 days). |
| Safety Issue: | |
| Description: | PK parameters will be derived using standard, non-compartmental methods |
| Measure: | Area under the plasma concentration-time curve from zero to 24 hours (AUC0-24) |
| Time Frame: | Samples will be collected on Cycle 1 Day 1,5 and Cycle 2 Day 5, Cycle 3 Day 5 and Cycle 5 Day 5 (each cycle is 21 days). |
| Safety Issue: | |
| Description: | PK parameters will be derived using standard, non-compartmental methods |
| Measure: | trough plasma concentration (Ctrough) |
| Time Frame: | Samples will be collected on Cycle 1 Day 1,5 and Cycle 2 Day 5, Cycle 3 Day 5 and Cycle 5 Day 5 (each cycle is 21 days). |
| Safety Issue: | |
| Description: | PK parameters will be derived using standard, non-compartmental methods |
| Measure: | Objective response rate (ORR) |
| Time Frame: | Assessed every 9 weeks with RECIST from the first dose of adavosertib until disease progression. Expected to be for up to 3 months. |
| Safety Issue: | |
| Description: | Defined as the proportion of subjects who have a best overall response of confirmed complete response (CR) or confirmed partial response (PR) |
| Measure: | Disease control rate (DCR) |
| Time Frame: | Assessed every 9 weeks with RECIST from the first dose of adavosertib until disease progression. Expected to be for up to 3 months. |
| Safety Issue: | |
| Description: | Defined as the proportion of subjects who have a best overall response of confirmed CR,confirmed PR, or stable disease (SD) |
| Measure: | Duration of response (DoR) |
| Time Frame: | Assessed every 9 weeks with RECIST from the first dose of adavosertib until disease progression. Expected to be for up to 3 months. |
| Safety Issue: | |
| Description: | Defined as the duration from the date of first documentation of response (CR or PR), which is subsequently confirmed, to the date of documented disease progression or death due to any cause in the absence of disease progression |
| Measure: | Progressionfree free survival (PFS) |
| Time Frame: | Assessed every 9 weeks with RECIST from the first dose of adavosertib until disease progression. Expected to be for up to 3 months. |
| Safety Issue: | |
| Description: | Defined as the time from the first dose of study treatment until the date of objective disease progression or death by any cause (in the absence of progression), regardless of whether the subject withdraws from the study or receives another anti-cancer therapy prior to progression |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | AstraZeneca |
Last Updated
July 26, 2021
