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

NCT04462952 | Completed Phase 1

• 1 other identifier: D601HC00008
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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 parts, monotherapy (part A) and chemotherapy combination (part B). At least 3, or up to 6, evaluable Japanese patients with advanced solid tumours will be enrolled in each cohort to confirm the tolerability.

Conditions

Advanced Solid Tumours

Outcome Measures

Primary Outcomes (2)

• Incidence of Adverse events

  Investigate the safety and tolerability of adavosertib

  From the informed consent to 30 days post last dose

• Incidence of Dose-limiting toxicity (DLTs)

  Investigate the safety and tolerability of adavosertib

  From the first dose of Cycle 1 up to the assessment prior to the planned first dose of Cycle 2 (each cycle is 21 days for Part A and 28 days for Part B)

Secondary Outcomes (9)

• Maximum plasma drug concentration observed (Cmax).

  Part A:Samples will be collected on Cycle1Day1,5, C2D5, C3D5 and C5D5. Part B:Samples will be collected on C1D2,3 and even Cycle D2 for adavosertib and C1D1 for gemcitabine. (each cycle is 21 days for Part A, 28 days for Part B)

• Time of maximum plasma drug concentration observed (tmax).

  Part A:Samples will be collected on Cycle1Day1,5, C2D5, C3D5 and C5D5. Part B:Samples will be collected on C1D2,3 and even Cycle D2 for adavosertib and C1D1 for gemcitabine. (each cycle is 21 days for Part A, 28 days for Part B)

• Area under the plasma concentration-time curve from zero to 24 hours (AUC0-24).

  Part A:Samples will be collected on Cycle1Day1,5, C2D5, C3D5 and C5D5. Part B:Samples will be collected on C1D2,3 and even Cycle D2 for adavosertib and C1D1 for gemcitabine. (each cycle is 21 days for Part A, 28 days for Part B)

• trough plasma concentration (Ctrough).

  Part A:Samples will be collected on Cycle1Day1,5, C2D5, C3D5 and C5D5. Part B:Samples will be collected on C1D2,3 and even Cycle D2 for adavosertib and C1D1 for gemcitabine. (each cycle is 21 days for Part A, 28 days for Part B)

• Objective response rate (ORR)

  Assessed every 9 weeks in Part A and every 8 weeks in Part B with RECIST from the first dose of adavosertib until disease progression. Expected to be for up to 3 months.

Other Outcomes (4)

• Part B: The ctDNA samples will be analysed for predictive biomarkers of response to treatment.

  Part B: at screening

• Part B: The ctDNA samples will be used for additional exploratory research for efficacy, tolerability, or safety assessment.

  Part B: Cycle 1 Day 1 (predose), discontinuation, and progression (each cycle is 28 days).

• Part A: Optional exploratory biomarker research in genetic samples from subjects who have consented to participate in the genetic analysis component of the study and exploratory biomarker research for efficacy, tolerability, or safety assessment.

  Part A: Cycle 1 Day 1 (each cycle is 21 days).

Study Arms (2)

Adavosertib (AZD1775) monotherapy

EXPERIMENTAL

Dose escalation of adavosertib monotherapy for patients with advanced solid tumours

Drug: Adavosertib (AZD1775)

Adavosertib (AZD1775) in combination with gemcitabine

EXPERIMENTAL

Dose escalation of adavosertib in combination with gemcitabine for patients with advanced solid tumours

Drug: Adavosertib (AZD1775)

Interventions

Adavosertib (AZD1775) DRUG

Adavosertib taken orally

Adavosertib (AZD1775) in combination with gemcitabine; Adavosertib (AZD1775) monotherapy

Eligibility Criteria

• Age: 20 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Part A : 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
• Part B : 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 and additionally, tumours for which gemcitabine is expected to be effective.
• Measurable or non-measurable disease according to RECIST v1.1

You may not qualify if:

• Use of anti-cancer treatment drug ≤21 days or 5 half-lives (whichever is shorter) prior to Cycle 1 Day 1
• Use of an investigational drug during the past 30 days or 5 half-lives (whichever is longer) prior to Cycle 1 Day 1
• 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 Cycle 1 Day 1 except for non-invasive malignancies
• Part B : Presence of apparent radiological findings for interstitial pneumonitis or pulmonary fibrosis with pulmonary symptoms

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Chūōku, 104-0045, Japan

Location

Related Publications (1)

• Kondo S, Katsuya Y, Yonemori K, Komuro K, Sugeno M, Kawata T, Ghiorghiu D, Meulendijks D, Yamamoto N. Safety, tolerability, pharmacokinetics, and antitumor activity of adavosertib in Japanese patients with advanced solid tumors: A phase I, open-label study. Cancer Treat Res Commun. 2024;39:100809. doi: 10.1016/j.ctarc.2024.100809. Epub 2024 Mar 24.

  PMID: 38593512 DERIVED

MeSH Terms

Interventions

adavosertib

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2020
• First Posted: July 8, 2020
• Study Start: June 24, 2020
• Primary Completion: September 22, 2021
• Study Completion: September 22, 2021
• Last Updated: July 25, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will share
• 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.

Locations

JP (1)