Clinical Trials /

Safety, Tolerability & Potential Anti-cancer Activity of Increasing Doses of AZD5363 in Different Treatment Schedules

NCT01226316

Description:

This study is designed to investigate the safety and tolerability of a new drug, AZD5363, in patients with advanced cancer - and to identify a dose and schedule that can be used in the future. This study will also investigate how the body handles AZD5363 (ie, how quickly the body absorbs and removes the drug). This study will also investigate anti-tumour activity of AZD5363 in patients with advanced / metastatic breast, gynaecological cancers or other solid cancers bearing either AKT1 / PIK3CA or PTEN mutation.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety, Tolerability & Potential Anti-cancer Activity of Increasing Doses of AZD5363 in Different Treatment Schedules
  • 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 Patients With Advanced Solid Malignancies.

Clinical Trial IDs

  • ORG STUDY ID: D3610C00001
  • SECONDARY ID: EudraCT number: 2010-022167-35
  • NCT ID: NCT01226316

Conditions

  • Advanced Solid Malignancy
  • Safety and Tolerability
  • Pharmacokinetics
  • Pharmacodynamics
  • Tumour Response
  • Advanced or Metastatic Breast Cancer
  • Ovarian Cancer
  • Cervical Cancer
  • Endometrial Cancer
  • PIK3CA
  • AKT1
  • PTEN
  • ER Positive
  • HER2 Positive

Interventions

DrugSynonymsArms
AZD5363Part A and B Schedule 1, Continuous dosing
AZD5363Parts A,B,C,D Schedule 2, Intermittent dosing
AZD5363Parts A and B Schedule 3, Intermittent dosing.
AZD5363Parts E and F, Intermittent dosing with Fulvestrant

Purpose

This study is designed to investigate the safety and tolerability of a new drug, AZD5363, in patients with advanced cancer - and to identify a dose and schedule that can be used in the future. This study will also investigate how the body handles AZD5363 (ie, how quickly the body absorbs and removes the drug). This study will also investigate anti-tumour activity of AZD5363 in patients with advanced / metastatic breast, gynaecological cancers or other solid cancers bearing either AKT1 / PIK3CA or PTEN mutation.

Detailed Description

      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 Patients with Advanced Solid Malignancies.
    

Trial Arms

NameTypeDescriptionInterventions
Part A and B Schedule 1, Continuous dosingExperimentalPart A: Ascending doses of AZD5363 administered orally, every day to define the maximum tolerated dose. Part B: Dose expansion phase, at the defined maximum tolerated dose or recommended dose from Part A.
  • AZD5363
Parts A,B,C,D Schedule 2, Intermittent dosingExperimentalPart A: Ascending doses of AZD5363 administered orally, twice daily, on a 7-day repeating regimen (4 days on, 3 days off and 2 days on, 5 days off), to define the maximum tolerated dose. Part B: Dose expansion phase, at the defined maximum tolerated dose or recommended dose from Part A (4 days on, 3 days off and 2 days on, 5 days off). Part C and D: AZD5363 orally, twice daily on an intermittent regimen (4 days on, 3 days off).
  • AZD5363
Parts A and B Schedule 3, Intermittent dosing.ExperimentalPart A: Ascending doses of AZD5363 administered orally, twice daily, on an alternative weekly regimen. Initiation of Schedule 3 is dependant on emerging clinical data. Part B: Dose expansion phase, at the defined maximum tolerated dose or recommended dose from Part A
  • AZD5363
Parts E and F, Intermittent dosing with FulvestrantExperimentalOral AZD5363 twice daily, 4 days on treatment, 3 days off treatment to cessation of therapy combined with background therapy of fulvestrant at its licensed dose of 500mg intramuscularly on days 1,15,29 and once monthly thereafter to cessation of therapy.
  • AZD5363

Eligibility Criteria

        Inclusion Criteria:

          -  Aged at least 18 years.

          -  Parts A,B: The presence of a solid, malignant tumour, excluding lymphoma, that is
             resistance to standard therapies or for which no standard therapies exist.

          -  ER+/HER2+ breast, ovarian, cervical, endometrial cancer, or other solid cancers,
             resistance to standard therapies with a PIK3CA gene mutation (Part C), AKT1 gene
             mutation (Part D) or a dysregulatory aberration on the PIK/AKT pathway (Part D),
             advanced or metastatic ER+ positive breast cancer that has an AKT1 gene mutation (Part
             E) or advanced or metastatic ER+ positive breast cancer that has a PTEN gene mutation
             (Part F).

          -  The presence of at least one lesion that can be accurately assessed at baseline by CT,
             MRI or plain X-ray and is suitable for repeated assessment. Estimated life expectancy
             of more than 12 weeks.

          -  Estimated life expectancy of more than 12 weeks.

        Exclusion Criteria:

          -  Clinically significant abnormalities of glucose metabolism.

          -  Spinal cord compression or brain metastases unless asymptomatic, treated and stable
             (not requiring steroids).

          -  Evidence of severe or uncontrolled systemic diseases, including active bleeding
             diatheses or active infections including hepatitis B, C and HIV.

          -  Evidence of clinically significant cardiac abnormalities, uncontrolled hypotension,
             left ventricular ejection fraction below the lower limit of normal for the site or
             experience of significant cardiac interventional procedures.

          -  A bad reaction to AZD5363 or any drugs similar to it in structure or class.
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Parts A,B,C,D,E & F : Safety and tolerability of AZD5363 in terms of adverse events and serious adverse events
Time Frame:Adverse events, serious adverse events and deaths will be collected from screening to 28 days after study drug discontinuation.
Safety Issue:
Description:

Secondary Outcome Measures

Measure:To characterise AZD5363 PK following single & multiple dosing by assessment of maximum plasma concentration,time to Cmax, terminal rate constant, terminal half life,area under the plasma concentration-time curve,plasma clearance & volume of distribution.
Time Frame:Sample:Part A&B:Cycle0Day1(predose,30min,1,2,4,6,8,10-12,24&48h postdose),C1D1(predose),D8/Last wkly dose(predose,30min,1,2,4,6,8,10-12h postdose),D15/Last wkly dose+7(predose),Part C,D,E&F:C1D1(predose,2,4h postdose)&D11(predose,2,4h postdose)
Safety Issue:
Description:
Measure:Parts A,B,C,D,E&F: To obtain a preliminary assessment of anti-tumour activity of AZD5363 via use of Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1
Time Frame:Tumour assessment by RECIST at 6,12,18,24wks then at 12 weekly intervals until discontinuation of study therapy
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Advanced solid malignancy,PIK3CA mutated,AKT1 mutated, PTEN mutation, PTEN alteration, metastatic,ER+,breast,ovarian,endometrial,AZD5363,AKT inhibitor,

Last Updated

March 1, 2018