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

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumor; Advanced Solid Malignancy
• Intervention / Treatment: Drug: AZD5363

• Study Type: Interventional
• Enrollment (Anticipated): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chuo-ku, Japan
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• 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.

Helpful Links

• d3610c00004_protocol_protocol amendments_Redacted_JPOL MP 11APR_Redacted....pdf

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (ACTUAL): July 1, 2014
• Study Completion (ACTUAL): July 1, 2014

Study Registration Dates

• First Submitted: April 11, 2011
• First Submitted That Met QC Criteria: May 13, 2011
• First Posted (ESTIMATE): May 16, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): April 26, 2016
• Last Update Submitted That Met QC Criteria: April 25, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Japanese; Phase 1; advanced solid tumor; AKT; Ascending
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: D3610C00004