AzTrials
AzTrials

Advanced Solid TumoursPhase 1NCT04462952

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

A Phase 1 study testing Adavosertib (AZD1775) in people with Advanced Solid Tumours, run by AstraZeneca at 1 site in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 20 to 120 years
Conditions the study is for
Advanced Solid Tumours
What is being tested?
Adavosertib (AZD1775)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteJapan
Study dates
24 Jun 2020to 22 Sep 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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
  • 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

Major Exclusion Criteria:

  • 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

Trial locations and contacts

1 site in 1 country.

Japan1 site

  • Research Site

    Chūōku, 104-0045

Other trials in Japan

About this study

Official title: A Phase I, Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-Tumour Activity of Adavosertib (AZD1775) in Monotherapy and in Combination With Chemotherapy in Japanese Patients With Advanced Solid Tumours

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.

Read the detailed description

Objectives:

Primary objective:

Part A:

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

Part B:

To assess the safety and tolerability, describe any dose-limiting toxicity (DLT) for adavosertib in combination with gemcitabine

Secondary objective:

To determine the PK profile of adavosertib plus gemcitabine To describe preliminary anti-tumour activity of adavosertib in combination with gemcitabine using the Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 To assess the drug interaction between adavosertib and gemcitabine

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 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. The total number of subjects will depend upon the available data in each cohort and the Safety Review Committee (SRC)'s decision.

Number of Subjects:

At least 3, or up to 6, evaluable Japanese patients with advanced solid tumours will be enrolled in each cohort.

Treatments and treatment duration:

Subjects in each part will receive the study treatments as described below:

Part A: Adavosertib by mouth (PO) once daily (QD) for 5 days ON and 2 days OFF for week 1 and 2 of a 21 days cycle.

Part B: Adavosertib PO will be taken QD on Days 2, 3, 9, 10, 16, and 17. Gemcitabine will be administered by intravenous infusion according to institutional standards on Days 1, 8, and 15 of each 28-day cycle.

Subjects will be allowed to continue adavosertib until disease progression, intolerable toxicity, or discontinuation criteria have been met.

Being tested
Adavosertib (AZD1775)

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Adavosertib (AZD1775)Drug

    Adavosertib taken orally

Study groups in NCT04462952
Study groupRoleWhat they receive
Adavosertib (AZD1775) monotherapyExperimentalDose escalation of adavosertib monotherapy for patients with advanced solid tumours
Receives: Drug: Adavosertib (AZD1775)
Adavosertib (AZD1775) in combination with gemcitabineExperimentalDose escalation of adavosertib in combination with gemcitabine for patients with advanced solid tumours
Receives: Drug: Adavosertib (AZD1775)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Adverse events

    Investigate the safety and tolerability of adavosertib

    Measured: From the informed consent to 30 days post last dose

  2. Incidence of Dose-limiting toxicity (DLTs)

    Investigate the safety and tolerability of adavosertib

    Measured: 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)

  1. Maximum plasma drug concentration observed (Cmax).

    PK parameters will be derived using standard, non-compartmental methods

    Measured: 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)

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

    PK parameters will be derived using standard, non-compartmental methods

    Measured: 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)

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

    PK parameters will be derived using standard, non-compartmental methods

    Measured: 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)

  4. trough plasma concentration (Ctrough).

    PK parameters will be derived using standard, non-compartmental methods

    Measured: 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)

  5. Objective response rate (ORR)

    Defined as the proportion of subjects who have a best overall response of confirmed complete response (CR) or confirmed partial response (PR)

    Measured: 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.

  6. Disease control rate (DCR)

    Defined as the proportion of subjects who have a best overall response of confirmed CR,confirmed PR, or stable disease (SD)

    Measured: 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.

  7. Duration of response (DoR)

    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

    Measured: 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.

  8. Progressionfree free survival (PFS)

    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

    Measured: Assessed every 9 weeks with RECIST from the first dose of adavosertib until disease progression. Expected to be for up to 3 months.

  9. Part B: the drug interaction between adavosertib and gemcitabine.

    PK parameters will be derived using standard, non-compartmental methods

    Measured: Part B : Samples will be collected on Cycle 1 Day 2,3 and even Cycle Day 2 for adavosertib and Cycle 1 Day 1 for gemcitabine. (each cycle is 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jul 2020
  2. Study start24 Jun 2020
  3. Primary completion22 Sep 2021
  4. Study completion22 Sep 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04462952
Sponsor's protocol ID
D601HC00008
Status last verified
Jul 2022
First submitted
17 Jun 2020
Last updated
25 Jul 2022
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 38593512

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Adavosertib (AZD1775) in people with Advanced Solid Tumours, run by AstraZeneca at 1 site in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Adverse events (time frame: From the informed consent to 30 days post last dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04462952, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in