Clinical trial NCT01353781: Open Label Phase 1 Study in Japan for Patient With Advanced Solid Malignancies
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Malignancy
Advanced Solid Tumor
Keywords: Phase 1
advanced solid tumor
AKT
Ascending
Japanese
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2011-05-16
Enrollment: 39
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: To investigate the safety and tolerability of AZD5363 to define a Recommended Dose (RD) when given orally
timeFrame: 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 outcomes:
measure: To define the maximum tolerated dose (MTD) if possible or biological effective dose in Japanese patients with advanced solid malignancies.
timeFrame: once 2 or more participants experience a DLT a dose level during the study period (within approx 20 months)
measure: To characterise the pharmacokinetics parameters Cmin
timeFrame: PK measurements on Cycle 0 Day 1/2/3 and Cycle 1 Day 1/8/15.
measure: 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
timeFrame: 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.
measure: To characterise the pharmacokinetics parameters(Cmax)
timeFrame: PK measurements on Cycle 0 Day 1/2/3 and Cycle 1 Day 1/8/15.
measure: To characterise the pharmacokinetics parameters tmax
timeFrame: PK measurements on Cycle 0 Day 1/2/3 and Cycle 1 Day 1/8/15.
measure: To characterise the pharmacokinetics parameters AUC
timeFrame: PK measurements on Cycle 0 Day 1/2/3 and Cycle 1 Day 1/8/15.
measure: To characterise the pharmacokinetics parameters CL/F
timeFrame: PK measurements on Cycle 0 Day 1/2/3 and Cycle 1 Day 1/8/15.
measure: To characterise the pharmacokinetics parameters Vz/F
timeFrame: PK measurements on Cycle 0 Day 1/2/3 and Cycle 1 Day 1/8/15.
Other outcomes:
Locations:
city: Chuo-ku
country: Japan
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Paul Stockman, MD
role: STUDY_DIRECTOR
References:
citation: Davies BR, Guan N, Logie A, Crafter C, Hanson L, Jacobs V, James N, Dudley P, Jacques K, Ladd B, D'Cruz CM, Zinda M, Lindemann J, Kodaira M, Tamura K, Jenkins EL. Tumors with AKT1E17K Mutations Are Rational Targets for Single Agent or Combination Therapy with AKT Inhibitors. Mol Cancer Ther. 2015 Nov;14(11):2441-51. doi: 10.1158/1535-7163.MCT-15-0230. Epub 2015 Sep 8.