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

AstraZeneca1 site in 1 country39 target enrollmentJune 2011

ConditionsAdvanced Solid Malignancy Advanced Solid Tumor

InterventionsAZD5363

DrugsAZD5363

Overview

Phase: Phase 1
Intervention: AZD5363
Conditions: Advanced Solid Malignancy
Sponsor: AstraZeneca
Enrollment: 39
Locations: 1
Primary Endpoint: To investigate the safety and tolerability of AZD5363 to define a Recommended Dose (RD) when given orally
Status: Completed
Last Updated: 10 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

June 2011

End Date

July 2014

Last Updated

10 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

AstraZeneca

Responsible Party

Sponsor

Eligibility Criteria

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

Arms & Interventions

AZD5363

Ascending doses of AZD5363 administered orally to patients to define the maximum tolerated dose (MTD)

Intervention: AZD5363

Outcomes

Primary Outcomes

To investigate the safety and tolerability of AZD5363 to define a Recommended Dose (RD) when given orally

Time Frame: 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

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

Secondary Outcomes

To define the maximum tolerated dose (MTD) if possible or biological effective dose in Japanese patients with advanced solid malignancies.(once 2 or more participants experience a DLT a dose level during the study period (within approx 20 months))
To characterise the pharmacokinetics parameters(Cmax)(PK measurements on Cycle 0 Day 1/2/3 and Cycle 1 Day 1/8/15.)
To characterise the pharmacokinetics parameters AUC(PK measurements on Cycle 0 Day 1/2/3 and Cycle 1 Day 1/8/15.)
To characterise the pharmacokinetics parameters Vz/F(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(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 tmax(PK measurements on Cycle 0 Day 1/2/3 and Cycle 1 Day 1/8/15.)
To characterise the pharmacokinetics parameters CL/F(PK measurements on Cycle 0 Day 1/2/3 and Cycle 1 Day 1/8/15.)
To characterise the pharmacokinetics parameters Cmin(PK measurements on Cycle 0 Day 1/2/3 and Cycle 1 Day 1/8/15.)