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
3 other identifiers
interventional
285
10 countries
34
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Dec 2010
Longer than P75 for phase_1
34 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 21, 2010
CompletedFirst Posted
Study publicly available on registry
October 22, 2010
CompletedStudy Start
First participant enrolled
December 1, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 26, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
December 3, 2024
CompletedJune 29, 2025
June 1, 2025
8.4 years
October 21, 2010
June 25, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (7)
Parts A,B,C,D,E & F : Safety and tolerability of AZD5363 in terms of adverse events and serious adverse events
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
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)
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
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
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).
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).
Multiple Gated Acquisition (MUGA) or Echocardiogram assessments to be carried out from screening until study drug discontinuation
Secondary Outcomes (2)
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.
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
Tumour assessment by RECIST at 6,12,18,24wks then at 12 weekly intervals until discontinuation of study therapy
Study Arms (4)
Part A and B Schedule 1, Continuous dosing
EXPERIMENTALPart 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.
Parts A,B,C,D Schedule 2, Intermittent dosing
EXPERIMENTALPart 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).
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
Parts E and F, Intermittent dosing with Fulvestrant
EXPERIMENTALOral 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.
Interventions
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (34)
Research Site
Los Angeles, California, 90089, United States
Research Site
Stanford, California, 94304, United States
Research Site
West Hollywood, California, 90048, United States
Research Site
Aurora, Colorado, 80045, United States
Research Site
Boston, Massachusetts, 02215, United States
Research Site
New York, New York, 10022, United States
Research Site
Oklahoma City, Oklahoma, 73104, United States
Research Site
Portland, Oregon, 97239, United States
Research Site
Charleston, South Carolina, 29425, United States
Research Site
Nashville, Tennessee, 37203, United States
Research Site
Nashville, Tennessee, 37204, United States
Research Site
Houston, Texas, 77030, United States
Research Site
Edmonton, Alberta, T6G 1Z2, Canada
Research Site
Vancouver, British Columbia, V5Z 4E6, Canada
Research Site
Toronto, Ontario, M5G 2M9, Canada
Research Site
Montreal, Quebec, H4A 3T2, Canada
Research Site
København Ø, 2100, Denmark
Research Site
Paris, 75248, France
Research Site
Pierre-Bénite, 69310, France
Research Site
Villejuif, 94805, France
Research Site
Milan, 20141, Italy
Research Site
Napoli, 80131, Italy
Research Site
Prato, 59100, Italy
Research Site
Chūōku, 104-0045, Japan
Research Site
Kashiwa, 277-8577, Japan
Research Site
Kōtoku, 135-8550, Japan
Research Site
Sapporo, 060-8638, Japan
Research Site
Amsterdam, 1066 CX, Netherlands
Research Site
Singapore, 119228, Singapore
Research Site
Madrid, 08035, Spain
Research Site
Madrid, 28041, Spain
Research Site
Valencia, 46010, Spain
Research Site
Manchester, M20 4BX, United Kingdom
Research Site
Sutton, SM2 5PT, United Kingdom
Related Publications (4)
Smyth LM, Reichel JB, Tang J, Patel JAA, Meng F, Selcuklu DS, Houck-Loomis B, You D, Samoila A, Schiavon G, Li BT, Razavi P, Piscuoglio S, Reis-Filho JS, Taylor BS, Baselga J, Solit DB, Hyman DM, Berger MF, Chandarlapaty S. Utility of Serial cfDNA NGS for Prospective Genomic Analysis of Patients on a Phase I Basket Study. JCO Precis Oncol. 2021 Jan 8;5:PO.20.00184. doi: 10.1200/PO.20.00184. eCollection 2021.
PMID: 34250397DERIVEDSmyth LM, Batist G, Meric-Bernstam F, Kabos P, Spanggaard I, Lluch A, Jhaveri K, Varga A, Wong A, Schram AM, Ambrose H, Carr TH, de Bruin EC, Salinas-Souza C, Foxley A, Hauser J, Lindemann JPO, Maudsley R, McEwen R, Moschetta M, Nikolaou M, Schiavon G, Razavi P, Banerji U, Baselga J, Hyman DM, Chandarlapaty S. Selective AKT kinase inhibitor capivasertib in combination with fulvestrant in PTEN-mutant ER-positive metastatic breast cancer. NPJ Breast Cancer. 2021 Apr 16;7(1):44. doi: 10.1038/s41523-021-00251-7.
PMID: 33863913DERIVEDSmyth LM, Tamura K, Oliveira M, Ciruelos EM, Mayer IA, Sablin MP, Biganzoli L, Ambrose HJ, Ashton J, Barnicle A, Cashell DD, Corcoran C, de Bruin EC, Foxley A, Hauser J, Lindemann JPO, Maudsley R, McEwen R, Moschetta M, Pass M, Rowlands V, Schiavon G, Banerji U, Scaltriti M, Taylor BS, Chandarlapaty S, Baselga J, Hyman DM. Capivasertib, an AKT Kinase Inhibitor, as Monotherapy or in Combination with Fulvestrant in Patients with AKT1 E17K-Mutant, ER-Positive Metastatic Breast Cancer. Clin Cancer Res. 2020 Aug 1;26(15):3947-3957. doi: 10.1158/1078-0432.CCR-19-3953. Epub 2020 Apr 20.
PMID: 32312891DERIVEDBanerji U, Dean EJ, Perez-Fidalgo JA, Batist G, Bedard PL, You B, Westin SN, Kabos P, Garrett MD, Tall M, Ambrose H, Barrett JC, Carr TH, Cheung SYA, Corcoran C, Cullberg M, Davies BR, de Bruin EC, Elvin P, Foxley A, Lawrence P, Lindemann JPO, Maudsley R, Pass M, Rowlands V, Rugman P, Schiavon G, Yates J, Schellens JHM. A Phase I Open-Label Study to Identify a Dosing Regimen of the Pan-AKT Inhibitor AZD5363 for Evaluation in Solid Tumors and in PIK3CA-Mutated Breast and Gynecologic Cancers. Clin Cancer Res. 2018 May 1;24(9):2050-2059. doi: 10.1158/1078-0432.CCR-17-2260. Epub 2017 Oct 24.
PMID: 29066505DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Gaia Schiavon, MSD
AstraZeneca
- PRINCIPAL INVESTIGATOR
Udai Banerji, MD, PhD
Institute of Cancer Research, United Kingdom
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 21, 2010
First Posted
October 22, 2010
Study Start
December 1, 2010
Primary Completion
April 26, 2019
Study Completion
December 3, 2024
Last Updated
June 29, 2025
Record last verified: 2025-06
Data Sharing
- IPD Sharing
- Will share
- 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
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.