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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01226316
Recruitment Status : Active, not recruiting
First Posted : October 22, 2010
Last Update Posted : July 15, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE October 21, 2010
First Posted Date  ICMJE October 22, 2010
Last Update Posted Date July 15, 2021
Actual Study Start Date  ICMJE December 1, 2010
Actual Primary Completion Date April 26, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 9, 2016)
  • 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 21, 2010)
  • 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).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 9, 2016)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 21, 2010)
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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability & Potential Anti-cancer Activity of Increasing Doses of AZD5363 in Different Treatment Schedules
Official Title  ICMJE 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
Brief Summary 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 20, 2019)
285
Original Estimated Enrollment  ICMJE
 (submitted: October 21, 2010)
84
Estimated Study Completion Date  ICMJE December 31, 2021
Actual Primary Completion Date April 26, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Denmark,   France,   Italy,   Japan,   Netherlands,   Singapore,   Spain,   United Kingdom,   United States
Removed Location Countries Germany,   Sweden
 
Administrative Information
NCT Number  ICMJE NCT01226316
Other Study ID Numbers  ICMJE D3610C00001
EudraCT number: 2010-022167-35
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gaia Schiavon, MSD AstraZeneca
Principal Investigator: Udai Banerji, MD, PhD Institute of Cancer Research, United Kingdom
PRS Account AstraZeneca
Verification Date July 2021

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