AKT Inhibitor in Oestrogen Positive Breast Cancer | Completed
AKT Inhibitor in Oestrogen Positive... | Completed
AKT Inhibitor in Oestrogen Positive Breast Cancer
STAKT

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Medical Conditions
  • Invasive Breast Cancer
Primary Contact Details
Unfortunately contact details are not available for this trial.
Recruitment Status
Completed
Trial source and source ID number
NCT02077569
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Summary
To compare the effect of four and a half days treatment of a range of doses of AZD5363 on selected markers of the AKT pathway and anti-proliferation compared with placebo in oestrogen receptor positive breast cancers.

To assess the tolerability of four and a half days treatment of AZD5363.
Research Details
  • The principal research questions to be addressed are whether (or not) AZD5363 is "hitting its therapeutic target" sufficiently and to the extent that is required to produce efficacy in pre-clinical experiments.

    The primary endpoint markers have been selected to determine this.

    Reductions in markers of the AKT pathway and increases in markers of anti-proliferation will characterise the degree of biological activity arising from the inhibition of AKT across a range of doses of AZD5363.
Phase
Phase 2
Study Design
Sorry, this information is not available
Study Type
Interventional
Intervention
Drug : AZD5363

Study Arm Groups : AZD5363 480mg, Placebo, AZD360mg, AZD5363 240mg

Intervention Type
See Interventions above
Primary Outcome Measures
    Primary endpoint: Pharmacodynamic biomarker analysis in tumour tissue to assess the biological effect of AZD5363 on markers of anti-proliferation and the AKT pathway; Up to 42 months: Stage 1: up to 60 participants in up to 20 months. Stage 1 biomarker analysis early in Stage 2. Stage 2 proceeds where reduction in 1 of the 3 primary biomarkers. Stage 2: up to 60 participants in up to 16 months.
Secondary Outcome Measures
    Compare anti-proliferative effect on markers of the AKT pathway after 4&1/2days treatment at 3 different doses of AZD5363 vs placebo in Er +ve breast cancers; Up to 42 months. Stage 1: up to 60 participants in up to 20 months. Stage 2: up to 60 participants in up to 16 months.; Compare direct effect on markers of the AKT pathway after 4&1/2days treatment at 3 different doses of AZD5363 vs placebo in Er +ve breast cancers; Up to 42 months. Stage 1: up to 60 participants in up to 20 months. Stage 2: up to 60 participants in up to 16 months.; To measure tolerability and toxicity following short term (four and a half days) exposure to AZD5363; Up to 42 months. Stage 1: up to 60 participants in up to 20 months. Stage 2: up to 60 participants in up to 16 months.
Publication(s)
Sorry, this information is not available
Result Reports
Check availability of results on the Clinicaltrials.gov website
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Gender
Female
Age Range
18 Years - N/A
Who Can Participate
Patients
Number of Participants
Sorry, this information is not available
Participant Inclusion Criteria
    Inclusion Criteria:

    1. Written informed consent

    2. WHO performance status 0-1.

    3. Able to swallow & retain oral medication.

    4. Patients who fall in to either category (a) or (b):

    1. Post-menopausal patients

    2. Pre-menopausal patients who also meet at least one of the criteria (i), (ii) or (iii) below:

    i) hysterectomy or bilateral fallopian tube ligation at least 6 weeks ago plus a negative pregnancy test.

    ii) true abstinence iii) willing to have pregnancy testing and use 2 forms of contraception

    5. Female patients, aged 18 years and over, with histological confirmation of ER positive invasive breast carcinoma.

    6. Stage 1/2/3 or Stage 4 with primary tumour in the breast amenable to biopsies. New primary breast tumours (ipsi- or contra-lateral) despite prior endocrine treatment for an earlier primary breast tumour with at least 12 months interval between cessation of endocrine therapy and Visit 1 are eligible.

    7. Scheduled to have chemotherapy based on tumour characteristics and local treatment protocols.

    8. Tumours large enough to provide sufficient tissue to be taken by core-cut or tru-cut biopsy to provide tissue sections for the marker assays.

    Exclusion Criteria:

    1. Prior treatment for breast cancer except new primary breast tumours arising despote prior endocrine treatment for an earlier primary breas tumour with at least 12 months interval between cessation of endocrine therapy and Visit 1 (see inclusion criteria 6).

    2. Known ER negative tumour.

    3. Female patients with histological confirmation of ER+ve invasive breast carcinoma not scheduled to have chemotherapy

    4. Exposure to potent inhibitors or inducers of CYP3A4 or CYP2D6 or substrates of CYP3A4 within 2 weeks before the first dose of study treatment (3 weeks for St Johns Wort).

    5. Clinically significant abnormalities of glucose metabolism

    6. Major surgery (excluding placement of vascular access) within 4 weeks before the first dose of study treatment.

    7. Spinal cord compression or brain metastases.

    8. Evidence of severe or uncontrolled systemic disease.

    9. Any of the following cardiac criteria:

    - Mean resting corrected QT interval (QTc)>450 msec obtained from 3 consecutive ECGs; - Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG

    - Any factors that increase the risk of QTc prolongation or risk of arrhythmic events.

    - Any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure NYHA Grade 2.

    - Uncontrolled hypotension.

    10. Absolute neutrophil count <1.5 x 10,000,000,000/L

    11. Platelet count <100 x 10,000,000,000/L.

    12. Haemoglobin <90 g/L

    13. ALT >2.5 times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases.

    14. Elevated ALP is not exclusionary if due to the presence of bone metastasis and liver function is otherwise considered adequate

    15. Total bilirubin >1.5 times ULN if no liver metastases or >3 times ULN in the presence of liver metastases.

    16. Creatinine >1.5 times ULN concurrent with creatinine clearance <50 ml/min; confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN

    17. Proteinuria >3+ on dipstick analysis.

    18. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD5363.

    19. History of hypersensitivity to active or inactive excipients of AZD5363 or drugs with a similar chemical structure or class to AZD5363.

    20. Current disease or condition known to interfere with absorption, distribution, metabolism or excretion of drugs.

    21. Past medical history of interstitial lung disease, drug induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.

    22. Evidence of dementia, altered mental status or any psychiatric condition that would prohibit understanding or rendering of informed consent

    23. Previous allogeneic bone marrow transplant.

    24. Known immunodeficiency syndrome.

    25. Pregnant or lactating patients
Participant Exclusion Criteria
This is in the inclusion criteria above
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Trial Location(s)
Leicester Royal Infirmary
Leicester
England
LE1 5WW
Edinburgh Cancer Centre at Western General Hospital
Edinburgh
Scotland
EH4 2XU
St. James University Hospital, Department of Neurology
Leeds
LS9 7TF
Rheumatology Department, Poole Hospital NHS Trust
Poole
BH15 2JB
Liverpool
Merseyside
L7 8XP
Royal Bournemouth Hospital
Bournemouth
Dorset
BH7 7DW
Pfizer Investigational Site
Birmingham
B15 2TT
Sheffield
S10 2SJ
GSK Investigational Site
Derby
DE22 3DT
Sutton-in-Ashfield
NG17 4JL
Plymouth Hospitals NHS Trust
Plymouth
Devon
PL6 8DH
Trial Contact(s)
Primary Trial Contact
Sorry, this information is not available
Other Trial Contacts
Sorry, this information is not available
Countries Recruiting
United Kingdom
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Scientific Title
The Short Term Effects of an AKT Inhibitor (AZD5363) on Biomarkers of the AKT Pathway and Anti-tumour Activity in a Breast Cancer Paired Biopsy Study
EudraCT Number
Not available for this trial
Funder(s)
  • AstraZeneca
  • Cancer Research UK
  • National Cancer Research Network
Other Study ID Numbers
12076
Sponsor(s)
University of Nottingham
Key Dates

Recruitment Start Date

Jan 2014

Recruitment End Date

Feb 2017

Trial Start Date
Date Not Available
Trial End Date
Date Not Available
Date added to source

16 Jan 2014

Date updated in source

03 May 2017