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

NCT ID: NCT01226316

Last Updated: 2025-06-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

285 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-12-01

Study Completion Date

2024-12-03

Brief Summary

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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

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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.

Conditions

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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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

AZD5363

Intervention Type 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.

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).

Group Type EXPERIMENTAL

AZD5363

Intervention Type 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.

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

Group Type EXPERIMENTAL

AZD5363

Intervention Type DRUG

Optional additional schedule. Patients will be given AZD5363 administered orally. Regimen to be determined in response to emerging clinical findings.

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.

Group Type EXPERIMENTAL

AZD5363

Intervention Type 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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

AZD5363

Optional additional schedule. Patients will be given AZD5363 administered orally. Regimen to be determined in response to emerging clinical findings.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gaia Schiavon, MSD

Role: STUDY_DIRECTOR

AstraZeneca

Udai Banerji, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute of Cancer Research, United Kingdom

Locations

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Research Site

Los Angeles, California, United States

Site Status

Research Site

Stanford, California, United States

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West Hollywood, California, United States

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Aurora, Colorado, United States

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Boston, Massachusetts, United States

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New York, New York, United States

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Oklahoma City, Oklahoma, United States

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Portland, Oregon, United States

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Charleston, South Carolina, United States

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Nashville, Tennessee, United States

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Nashville, Tennessee, United States

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Houston, Texas, United States

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Edmonton, Alberta, Canada

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Vancouver, British Columbia, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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København Ø, , Denmark

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Paris, , France

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Pierre-Bénite, , France

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Villejuif, , France

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Milan, , Italy

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Napoli, , Italy

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Prato, , Italy

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Chūōku, , Japan

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Kashiwa, , Japan

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Kōtoku, , Japan

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Sapporo, , Japan

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Amsterdam, , Netherlands

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Singapore, , Singapore

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Madrid, , Spain

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Madrid, , Spain

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Valencia, , Spain

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Manchester, , United Kingdom

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Sutton, , United Kingdom

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Countries

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United States Canada Denmark France Italy Japan Netherlands Singapore Spain United Kingdom

References

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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.

Reference Type DERIVED
PMID: 34250397 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33863913 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32312891 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29066505 (View on PubMed)

Other Identifiers

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EudraCT number: 2010-022167-35

Identifier Type: -

Identifier Source: secondary_id

2010-022167-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D3610C00001

Identifier Type: -

Identifier Source: org_study_id

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