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

Advanced Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01353781
• Other study ID #: D3610C00004
• Status: Completed
• Phase: Phase 1
• First received: April 11, 2011
• Last updated: April 25, 2016
• Start date: June 2011
• Est. completion date: July 2014

Study information

• Verified date: April 2016
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and WelfareJapan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Solid Malignancy
• Advanced Solid Tumor
• Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Japan	Research Site	Chuo-ku

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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)	Yes
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No

External Links

•   d3610c00004_protocol_protocol amendments_Redacted_JPOL MP 11APR_Redacted....pdf