Study of Adavosertib(AZD1775) in Japanese Patients With Advanced Solid Tumours

• ClinicalTrials.gov Identifier: NCT04462952
• Recruitment Status: Active, not recruiting
• First Posted: July 8, 2020
• Last Update Posted: July 26, 2021
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumours	Drug: Adavosertib (AZD1775)	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• 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
• Actual Study Start Date: June 24, 2020
• Estimated Primary Completion Date: July 15, 2021
• Estimated Study Completion Date: July 15, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Adavosertib monotherapy; Dose escalation of adavosertib monotherapy for patients with advanced solid tumours	Drug: Adavosertib (AZD1775); Adavosertib taken orally

Outcome Measures

Primary Outcome Measures :

1. Incidence of Adverse events [ Time Frame: From the informed consent to 30 days post last dose ]
   Investigate the safety and tolerability of adavosertib
2. Incidence of Dose-limiting toxicity (DLTs) [ Time Frame: From the first dose of adavosertib up to the assessment prior to the planned first dose of Cycle 2 (each cycle is 21 days) ]
   Investigate the safety and tolerability of adavosertib

Secondary Outcome Measures :

1. 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). ]
   PK parameters will be derived using standard, non-compartmental methods
2. 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). ]
   PK parameters will be derived using standard, non-compartmental methods
3. 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). ]
   PK parameters will be derived using standard, non-compartmental methods
4. 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). ]
   PK parameters will be derived using standard, non-compartmental methods
5. 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. ]
   Defined as the proportion of subjects who have a best overall response of confirmed complete response (CR) or confirmed partial response (PR)
6. 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. ]
   Defined as the proportion of subjects who have a best overall response of confirmed CR,confirmed PR, or stable disease (SD)
7. 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. ]
   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
8. 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. ]
   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

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 120 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Japan

Research Site

Chuo-ku, Japan, 104-0045

Sponsors and Collaborators

AstraZeneca

More Information

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT04462952
• Other Study ID Numbers: D601HC00008
• First Posted: July 8, 2020
• Last Update Posted: July 26, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neoplasms; Adavosertib; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action