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

Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01226316
• Other study ID #: D3610C00001
• Secondary ID: EudraCT number:
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: December 1, 2010
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 285
• Est. completion date: December 31, 2024
• Est. primary completion date: April 26, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

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.

Related Conditions & MeSH terms

• Advanced or Metastatic Breast Cancer
• Advanced Solid Malignancy
• AKT1
• Cervical Cancer
• Endometrial Cancer
• Endometrial Neoplasms
• ER Positive
• HER2 Positive
• Neoplasms
• Ovarian Cancer
• Pharmacodynamics
• Pharmacokinetics
• PIK3CA
• PTEN
• Safety and Tolerability
• Tumour Response

Intervention

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

Locations

Country	Name	City	State
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
Denmark	Research Site	København Ø
France	Research Site	Paris Cedex 5
France	Research Site	Pierre Benite CEDEX
France	Research Site	Villejuif
Italy	Research Site	Milan
Italy	Research Site	Napoli
Italy	Research Site	Prato
Japan	Research Site	Chuo-ku
Japan	Research Site	Kashiwa
Japan	Research Site	Koto-ku
Japan	Research Site	Sapporo-shi
Netherlands	Research Site	Amsterdam
Singapore	Research Site	Singapore
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Valencia
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Sutton
United States	Research Site	Aurora	Colorado
United States	Research Site	Boston	Massachusetts
United States	Research Site	Charleston	South Carolina
United States	Research Site	Houston	Texas
United States	Research Site	Los Angeles	California
United States	Research Site	Nashville	Tennessee
United States	Research Site	Nashville	Tennessee
United States	Research Site	New York	New York
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Portland	Oregon
United States	Research Site	Stanford	California
United States	Research Site	West Hollywood	California

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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
Primary	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
Primary	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
Primary	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.
Primary	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.
Primary	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	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)
Secondary	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

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