Clinical trial NCT04462952: 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 Monotherapy and in Combination With Chemotherapy in Japanese Patients With Advanced Solid Tumours
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumours
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2020-07-08
Enrollment: 6
Sex: ALL
Minimum age (years): 20
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

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.

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
* 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

Primary outcomes:
measure: Incidence of Adverse events
timeFrame: From the informed consent to 30 days post last dose
measure: Incidence of Dose-limiting toxicity (DLTs)
timeFrame: 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:
measure: Maximum plasma drug concentration observed (Cmax).
timeFrame: 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)
measure: Time of maximum plasma drug concentration observed (tmax).
timeFrame: 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)
measure: Area under the plasma concentration-time curve from zero to 24 hours (AUC0-24).
timeFrame: 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)
measure: trough plasma concentration (Ctrough).
timeFrame: 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)
measure: Objective response rate (ORR)
timeFrame: 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.
measure: Disease control rate (DCR)
timeFrame: 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.
measure: Duration of response (DoR)
timeFrame: 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.
measure: Progressionfree free survival (PFS)
timeFrame: Assessed every 9 weeks with RECIST from the first dose of adavosertib until disease progression. Expected to be for up to 3 months.
measure: Part B: the drug interaction between adavosertib and gemcitabine.
timeFrame: 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)
Other outcomes:
measure: Part B: The ctDNA samples will be analysed for predictive biomarkers of response to treatment.
timeFrame: Part B: at screening
measure: Part B: The ctDNA samples will be used for additional exploratory research for efficacy, tolerability, or safety assessment.
timeFrame: Part B: Cycle 1 Day 1 (predose), discontinuation, and progression (each cycle is 28 days).
measure: 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.
timeFrame: Part A: Cycle 1 Day 1 (each cycle is 21 days).
measure: Part B:Exploratory analyses may be undertaken on the data generated from tumour tissue to identify biomarkers of sensitivity and resistance to treatment and to increase our understanding of the disease (consenting participants only.)
timeFrame: Part B: at screening
Locations:
city: Chuo-ku
country: Japan
facility: Research Site
Study officials:
References: