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

NCT01353781 | Completed Phase 1

• 1 other identifier: D3610C00004
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Solid Malignancy; Advanced Solid Tumor

Keywords

Phase 1; advanced solid tumor; AKT; Ascending; Japanese

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• 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 Cmin

  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(Cmax)

  PK measurements on Cycle 0 Day 1/2/3 and Cycle 1 Day 1/8/15.

• To characterise the pharmacokinetics parameters tmax

  PK measurements on Cycle 0 Day 1/2/3 and Cycle 1 Day 1/8/15.

Study Arms (1)

AZD5363

EXPERIMENTAL

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

Drug: AZD5363

Interventions

AZD5363 DRUG

Patients will be given AZD5363 capsules administered orally as a single dose, and then multiple twice-daily dosing following 3 to 7 days washout.

AZD5363

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Chūōku, Japan

Location

Related Publications (1)

• 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.

  PMID: 26351323 DERIVED

Related Links

• d3610c00004\_protocol\_protocol amendments\_Redacted\_JPOL MP 11APR\_Redacted....pdf

MeSH Terms

Interventions

capivasertib

Study Officials

• Paul Stockman, MD

  AstraZeneca

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2011
• First Posted: May 16, 2011
• Study Start: June 1, 2011
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: April 26, 2016

Record last verified: 2016-04

Locations

JP (1)