Open Label Phase 1 Study in Japan for Patient With Advanced Solid Malignancies

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumour activity of ascending doses of AZD5363 under adaptable dosing schedules in Japanese patients with advanced solid malignancies.

Official Title
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A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ascending Doses of AZD5363 Under Adaptable Dosing Schedules in Japanese Patients With Advanced Solid Malignancies

Conditions
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Advanced Solid Tumor, Advanced Solid Malignancy

Intervention / Treatment
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* Drug: AZD5363


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged at least 20 years Histological or cytological confirmation of a solid malignant tumour, excluding lymphoma, that is refractory to standard therapies or for which no standard therapies exist At least one lesion (measurable and/or non-measurable) that can be accurately assessed according to RECIST World Health Organisation (WHO) performance status 0-1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks Patients should be willing to remain in hospital until the completion of the first cycle including cycle 0, cycle 1, and cycle 2 Day1 (as cycle 1 Day 21) Exclusion Criteria: Clinically significant abnormalities of glucose metabolism as defined by any of the following: Diagnosis of diabetes mellitus type I or II (irrespective of management) Baseline fasting glucose value of ≥7 mmol/l (126mg/dL) Glycosylated haemoglobin (HbA1C) >6.5% Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids for at least 4 weeks prior to start of study treatment Inadequate bone marrow reserve or organ function Any evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses, or active infection With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD5363<br>Ascending doses of AZD5363 administered orally to patients to define the maximum tolerated dose (MTD) | Drug: AZD5363<br>* Patients will be given AZD5363 capsules administered orally as a single dose, and then multiple twice-daily dosing following 3 to 7 days washout.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate the safety and tolerability of AZD5363 to define a Recommended Dose (RD) when given orally | To investigate the safety and tolerability of AZD5363 to define a Recommended Dose (RD) when given orally, either as a continuous or an intermittent schedule, for further clinical evaluation when given to Japanese patients with advanced solid malignancies | All AEs will be collected throughout the study, from informed consent until 30 days after the end of study treatment. The total duration of this time frame can not be specified, as it depends on the number of treatments the subject may receive | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To define the maximum tolerated dose (MTD) if possible or biological effective dose in Japanese patients with advanced solid malignancies. | To define the maximum tolerated dose (MTD) if possible or biological effective dose in Japanese patients with advanced solid malignancies. A dose will be considered non-tolerated and dose escalation will cease if 2 or more of up to 6 evaluable patients experience a DLT at a dose level. Six evaluable patients are required to determine the MTD | once 2 or more participants experience a DLT a dose level during the study period (within approx 20 months) | 
| To characterise the pharmacokinetics parameters Cmin | To characterise the pharmacokinetics parameters Cmin of AZD5363 following a single administration and after multiple dosing when given orally to Japanese patients with advanced solid malignancies | PK measurements on Cycle 0 Day 1/2/3 and Cycle 1 Day 1/8/15. | 
| To obtain a preliminary assessment of the anti-tumour activity of AZD5363 by evaluation of tumour response using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 in Japanese patients with advanced solid malignancies | To obtain a preliminary assessment of the anti-tumour activity of AZD5363 by evaluation of tumour response using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 in Japanese patients with advanced solid malignancies. The total duration of this time frame can not be specified, as it depends on the number of treatments the subject may receive. | Assessed every 3 weeks for initial 2 cycles and every 6 weeks for later cycles for all subjects after start of study treatment until discontinuation of study treatment or withdrawal of consent. | 
| To characterise the pharmacokinetics parameters(Cmax) | To characterise the pharmacokinetics parameters Cmax of AZD5363 following a single administration and after multiple dosing when given orally to Japanese patients with advanced solid malignancies | PK measurements on Cycle 0 Day 1/2/3 and Cycle 1 Day 1/8/15. | 
| To characterise the pharmacokinetics parameters tmax | To characterise the pharmacokinetics parameters tmax of AZD5363 following a single administration and after multiple dosing when given orally to Japanese patients with advanced solid malignancies | PK measurements on Cycle 0 Day 1/2/3 and Cycle 1 Day 1/8/15. | 
| To characterise the pharmacokinetics parameters AUC | To characterise the pharmacokinetics parameters AUC factor of AZD5363 following a single administration and after multiple dosing when given orally to Japanese patients with advanced solid malignancies | PK measurements on Cycle 0 Day 1/2/3 and Cycle 1 Day 1/8/15. | 
| To characterise the pharmacokinetics parameters CL/F | To characterise the pharmacokinetics parameters CL/F factor of AZD5363 following a single administration and after multiple dosing when given orally to Japanese patients with advanced solid malignancies | PK measurements on Cycle 0 Day 1/2/3 and Cycle 1 Day 1/8/15. | 
| To characterise the pharmacokinetics parameters Vz/F | To characterise the pharmacokinetics parameters Vz/F of AZD5363 following a single administration and after multiple dosing when given orally to Japanese patients with advanced solid malignancies | PK measurements on Cycle 0 Day 1/2/3 and Cycle 1 Day 1/8/15. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, advanced solid tumor, AKT, Ascending, Japanese