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

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ClinicalTrials.gov Identifier: NCT01226316
Recruitment Status : Recruiting
First Posted : October 22, 2010
Last Update Posted : November 1, 2018
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

October 21, 2010
October 22, 2010
November 1, 2018
December 1, 2010
April 18, 2019   (Final data collection date for primary outcome 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. ]
  • Parts A,B,C,D,E & F : Safety and tolerability of AZD5363 in terms of death [ Time Frame: Deaths will be collected from screening to 28 days after study drug discontinuation ]
  • Parts A,B,C,D,E & F: Safety and tolerability of AZD5363 by assessing changes from baseline of laboratory data (clinical chemistry, haematology, urinalysis) [ Time Frame: Laboratory data will be collected from screening to 28 days after study drug discontinuation ]
  • Parts A,B,C,D,E & F: Safety and tolerability of AZD5363 in terms of changes from baseline in vital signs and in electrocardiogram (ECG) parameters [ Time Frame: Vital signs and ECGs will be recorded from screening to 28 days after study drug discontinuation ]
  • Parts A,B,C,D,E & F: Safety and tolerability of AZD5363 by assessing changes from baseline in electrocardiogram (ECG) parameters [ Time Frame: ECGs will be collected from screening to 28 days after study drug discontinuation. ]
  • Parts A,B,C,D,E & F: Safety and tolerability of AZD5363 by assessing changes from baseline of glucose laboratory parameters (Urine, serum and plasma glucose, glycosylated haemoglobin). [ Time Frame: Glucose parameters will be collected from screening to 28 days after study discontinuation. ]
  • Parts A,B,C,D,E & F: Safety and tolerability of AZD5363 by assessing left ventricular ejection fraction (LVEF). [ Time Frame: Multiple Gated Acquisition (MUGA) or Echocardiogram assessments to be carried out from screening until study drug discontinuation ]
  • To investigate the safety and tolerability of ascending doses of AZD5363 [ Time Frame: Routine safety assessments, ECG and Echo/MUGA throughout the period that patients receive AZD5363 and up to 30 days following cessation. ]
    To investigate the safety and tolerability of ascending doses of AZD5363 in terms of: adverse events, deaths, laboratory data, vital signs, ECG parameters and LVEF parameter changes in patients with advanced solid malignancies.
  • To obtain a preliminary assessment of anti-tumour activity of AZD5363 via use of Response Evaluation Criteria in Sold Tumours (RECIST). [ Time Frame: Tumour assessment by RECIST at 6 weekly intervals until discontinuation of study therapy ]
    To obtain a preliminary assessment of anti-tumour activity of AZD5363 via use of Response Evaluation Criteria in Sold Tumours (RECIST).
Complete list of historical versions of study NCT01226316 on ClinicalTrials.gov Archive Site
  • 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) ]
  • 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 ]
Characterise the pharmacokinetics of AZD5363 [ Time Frame: Multiple PK samplings within 3 days from receiving a single initial dose, and then within 15 days of receiving first multiple dose. ]
Characterise the pharmacokinetics of AZD5363 following a single administration and after multiple dosing by assessment of: time to maximum plasma concentration, terminal rate constant, terminal half life, area under plasma concentration time curve,plasma clearance and volume of distribution.
Not Provided
Not Provided
 
Safety, Tolerability & Potential Anti-cancer Activity of Increasing Doses of AZD5363 in Different Treatment Schedules
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
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.
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.
Interventional
Phase 1
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • 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
  • Drug: AZD5363
    Patients will receive a single dose of AZD5363, administered orally, followed by a 3-7 day wash-out period. Patients will then commence with twice-daily dosing, administered orally, every day, to cessation of therapy.
  • Drug: AZD5363
    Patients will be given AZD5363 administered orally as a single dose, followed by a 3-7 day wash-out period. Patients will then receive AZD5363 twice daily on 6 or fewer days per weekly regimen, to cessation of therapy. Parts C,D: Oral AZD5363 twice daily, 4 days on treatment, 3 days off treatment, to cessation of therapy.
  • Drug: AZD5363
    Optional additional schedule. Patients will be given AZD5363 administered orally. Regimen to be determined in response to emerging clinical findings.
  • Drug: AZD5363
    Patients will receive oral AZD5363 twice daily (4 days on 3 days off treatment)combined with background therapy of fulvestrant at licensed dose of 500mg intramuscularly on days 1,15,29 and once monthly thereafter.
  • Experimental: Part A and B Schedule 1, Continuous dosing
    Part 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.
    Intervention: Drug: AZD5363
  • Experimental: Parts A,B,C,D Schedule 2, Intermittent dosing
    Part 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).
    Intervention: Drug: AZD5363
  • Experimental: Parts A and B Schedule 3, Intermittent dosing.

    Part 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

    Intervention: Drug: AZD5363
  • Experimental: Parts E and F, Intermittent dosing with Fulvestrant
    Oral 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.
    Intervention: Drug: AZD5363
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
304
84
November 15, 2019
April 18, 2019   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years to 130 Years   (Adult, Older Adult)
No
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: Cancer Study Locator 877 400 4656 AstraZeneca@emergingmed.com
Canada,   Denmark,   France,   Germany,   Italy,   Japan,   Netherlands,   Singapore,   Spain,   Sweden,   United Kingdom,   United States
 
 
NCT01226316
D3610C00001
EudraCT number: 2010-022167-35
No
Not Provided
Not Provided
AstraZeneca
AstraZeneca
Not Provided
Study Director: Gaia Schiavon, MSD AstraZeneca
Principal Investigator: Udai Banerji, MD, PhD Institute of Cancer Research, United Kingdom
AstraZeneca
October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP