Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| EudraCT number: 2010-022167-35 | |||
| 2010-022167-35 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A and B Schedule 1, Continuous dosing | Experimental | 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. |
|
| Parts A,B,C,D Schedule 2, Intermittent dosing | Experimental | 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). |
|
| Parts A and B Schedule 3, Intermittent dosing. | Experimental | 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 |
|
| Parts E and F, Intermittent dosing with Fulvestrant | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD5363 | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Gaia Schiavon, MSD | AstraZeneca | Study Director |
| Udai Banerji, MD, PhD | Institute of Cancer Research, United Kingdom | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Los Angeles | California | 90089 | United States | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34250397 | Derived | 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. | |
| 33863913 |
| Label | URL |
|---|---|
| Related Info | View source |
Not provided
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.
Not provided
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
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
Not provided
Not provided
Not provided
Not provided
Not provided
|
| AZD5363 | Drug | 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. |
|
| AZD5363 | Drug | Optional additional schedule. Patients will be given AZD5363 administered orally. Regimen to be determined in response to emerging clinical findings. |
|
| AZD5363 | Drug | 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. |
|
| 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 |
| 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 | Naples | 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 |
| Derived |
| Smyth 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. |
| 32312891 | Derived | Smyth 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. |
| 29066505 | Derived | Banerji 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. |
| CSR Synopsis | View source |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D010051 | Ovarian Neoplasms |
| D002583 | Uterine Cervical Neoplasms |
| D016889 | Endometrial Neoplasms |
| D009477 | Hereditary Sensory and Autonomic Neuropathies |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D004701 | Endocrine Gland Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| D014594 | Uterine Neoplasms |
| D002577 | Uterine Cervical Diseases |
| D014591 | Uterine Diseases |
| D009421 | Nervous System Malformations |
| D009422 | Nervous System Diseases |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D011115 | Polyneuropathies |
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |
Not provided
Not provided
| ID | Term |
|---|---|
| C575618 | capivasertib |
Not provided
Not provided
Not provided