Invasive Breast CancerPhase 2STAKTNCT02077569
AKT Inhibitor in Oestrogen Positive Breast Cancer
A Phase 2 study testing AZD5363 in people with Invasive Breast Cancer, run by University of Nottingham at 11 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Invasive Breast Cancer
- What is being tested?
- AZD5363
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 11 sitesUnited Kingdom
- Study dates
- Jan 2014to 21 Feb 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent
- WHO performance status 0-1.
- Able to swallow \& retain oral medication.
- Patients who fall in to either category (a) or (b):
- Post-menopausal patients
- Pre-menopausal patients who also meet at least one of the criteria (i), (ii) or (iii) below:
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- hysterectomy or bilateral fallopian tube ligation at least 6 weeks ago plus a negative pregnancy test.
- true abstinence iii) willing to have pregnancy testing and use 2 forms of contraception
- Female patients, aged 18 years and over, with histological confirmation of ER positive invasive breast carcinoma.
- 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.
- Scheduled to have chemotherapy based on tumour characteristics and local treatment protocols.
- 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.
Who cannot join
- 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).
- Known ER negative tumour.
- Female patients with histological confirmation of ER+ve invasive breast carcinoma not scheduled to have chemotherapy
- 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).
- Clinically significant abnormalities of glucose metabolism
- Major surgery (excluding placement of vascular access) within 4 weeks before the first dose of study treatment.
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- Spinal cord compression or brain metastases.
- Evidence of severe or uncontrolled systemic disease.
- 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.
- Absolute neutrophil count <1.5 x 10,000,000,000/L
- Platelet count <100 x 10,000,000,000/L.
- Haemoglobin <90 g/L
- ALT >2.5 times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases.
- Elevated ALP is not exclusionary if due to the presence of bone metastasis and liver function is otherwise considered adequate
- Total bilirubin >1.5 times ULN if no liver metastases or >3 times ULN in the presence of liver metastases.
- 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
- Proteinuria >3+ on dipstick analysis.
- 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.
- History of hypersensitivity to active or inactive excipients of AZD5363 or drugs with a similar chemical structure or class to AZD5363.
- Current disease or condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
- 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.
- Evidence of dementia, altered mental status or any psychiatric condition that would prohibit understanding or rendering of informed consent
- Previous allogeneic bone marrow transplant.
- Known immunodeficiency syndrome.
- Pregnant or lactating patients
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United Kingdom11 sites
University Hospital Birmingahm
Birmingham, West Midlands, B15 2TT
Royal Bournemouth Hospital
Bournemouth, Dorset, BH7 7DW
Royal Derby Hospital
Derby, Derbyshire, DE22 3DT
Plymouth Hospitals NHS Trust
Derriford, Plymouth, Devon, PL6 8DH
Western General Hospital
Edinburgh, Lothian, EH4 2XU
Leeds St James Institue of Oncology
Leeds, West Yorkshire, LS9 7TF
Leicester Royal Infirmary
Leicester, Leicestershire, LE1 5WW
Royal Liverpool University Hospital
Liverpool, Merseyside, L7 8XP
Poole Hospital NHS Foundation Trust
Poole, Dorset, BH15 2JB
Sheffield Cancer Research Centre
Sheffield, South Yorkshire, S10 2SJ
Kingsmill Hospital
Sutton in Ashfield, Nottinghamshire, NG17 4JL
About this study
Official 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
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.
Read the detailed description
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.
- Conditions
- Invasive Breast Cancer
- Being tested
- AZD5363
- Keywords
- AKT inhibitor, AZD5363, Anti-tumour activity, Breast cancer, ER positive, Oestrogen positive, post menopausal, chemotherapy required, no prior cancer treatment
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD5363Drug
Stage 1: AZD5363 480mg or placebo twice daily oral dosing for 4 and 1/2 days (9 doses) Stage 2: AZD5363 360mg or 240mg daily oral dosing for 4 and 1/2 days (9 doses)
| Study group | Role | What they receive |
|---|---|---|
| AZD5363 480mg | Experimental | STAGE 1 ONLY AZD5363 480mg Twice daily dosing for 4 and 1/2 days (9 doses) Oral Capsule Receives: Drug: AZD5363 |
| Placebo | Placebo comparator | STAGE 1 ONLY Twice daily dosing for 4 and 1/2 days (9 doses) Oral Capsule Receives: Drug: AZD5363 |
| AZD360mg | Experimental | STAGE 2 AZD5363 360mg Twice daily dosing for 4 and 1/2 days (9 doses) Oral Capsule Receives: Drug: AZD5363 |
| AZD5363 240mg | Experimental | STAGE 2 AZD5363 240mg Twice daily dosing for 4 and 1/2 days (9 doses) Oral Capsule Receives: Drug: AZD5363 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary endpoint: Pharmacodynamic biomarker analysis in tumour tissue to assess the biological effect of AZD5363 on markers of anti-proliferation and the AKT pathway
Changes in pPRAS40, pGSK3b, Ki67
Measured: 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 outcomes (3)
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
By measuring biological changes in the tumour and circulation via measurement of changes in alternative biological markers which relate to the AKT pathway:
Tumour total and pAKT Tumour: cleaved caspase 3; pS6 (IHC); FOXO3a Blood (platelet-rich plasma): Total and pPRAS40; Total and pGSK3b; Total and pAKT.
Measured: 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
By measuring biological changes in the tumour and circulation via measurement of changes in alternative biological markers which relate to the AKT pathway:
Tumour total and pAKT Tumour: cleaved caspase 3; pS6 (IHC); FOXO3a Blood (platelet-rich plasma): Total and pPRAS40; Total and pGSK3b; Total and pAKT.
Measured: 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
Tolerability and toxicity will be measured following short term exposure to AZD5363 by incidence and severity of adverse events.
Participants will be monitored for adverse events during the study and for at least 30 days after the end of treatment.
Analysis of toxicity following the completion of Stage 1, taking into consideration that Stage 2 will use lower doses of AZD5363, and at the end of Stage 2.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2014 (estimated)
- Study startJan 2014
- Primary completion21 Feb 2017
- Study completion21 Feb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Invasive Breast CancerStudies of the same condition, open and under way.
- More trials run by University of NottinghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca, Cancer Research UK, National Cancer Research Network
- Responsible party
- Sponsor
- Investigators
- John FR Robertson, MD, Study chair, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02077569
- Sponsor's protocol ID
- 12076
- Acronym
- STAKT
- Status last verified
- May 2017
- First submitted
- 16 Jan 2014
- Last updated
- 4 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02077569
- Acronym / sponsor ID
- STAKT / 12076
- Conditions
- Invasive Breast Cancer
- Keywords
- AKT inhibitor, AZD5363, Anti-tumour activity, Breast cancer, ER positive, Oestrogen positive, post menopausal, chemotherapy required
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Collaborators
- AstraZeneca, Cancer Research UK, National Cancer Research Network
- Study start
- Jan 2014
- Primary completion
- 21 Feb 2017 (actual)
- Study completion
- 21 Feb 2017 (actual)
- First posted
- 4 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| AZD5363 480mg | Experimental | Drug: AZD5363STAGE 1 ONLY AZD5363 480mg Twice daily dosing for 4 and 1/2 days (9 doses) Oral Capsule |
| Placebo | Placebo comparator | Drug: AZD5363STAGE 1 ONLY Twice daily dosing for 4 and 1/2 days (9 doses) Oral Capsule |
| AZD360mg | Experimental | Drug: AZD5363STAGE 2 AZD5363 360mg Twice daily dosing for 4 and 1/2 days (9 doses) Oral Capsule |
| AZD5363 240mg | Experimental | Drug: AZD5363STAGE 2 AZD5363 240mg Twice daily dosing for 4 and 1/2 days (9 doses) Oral Capsule |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Written informed consent
- WHO performance status 0-1.
- Able to swallow \& retain oral medication.
- Patients who fall in to either category (a) or (b):
- Female patients, aged 18 years and over, with histological confirmation of ER positive invasive breast carcinoma.
Key exclusion criteria (29 listed)
- 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).
- Known ER negative tumour.
- Female patients with histological confirmation of ER+ve invasive breast carcinoma not scheduled to have chemotherapy
- 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).
- Clinically significant abnormalities of glucose metabolism
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD5363Stage 1: AZD5363 480mg or placebo twice daily oral dosing for 4 and 1/2 days (9 doses) Stage 2: AZD5363 360mg or 240mg daily oral dosing for 4 and 1/2 days (9 doses) | Drug | AZD360mg, AZD5363 240mg, AZD5363 480mg, Placebo |
Primary outcome
Primary endpoint: Pharmacodynamic biomarker analysis in tumour tissue to assess the biological effect of AZD5363 on markers of anti-proliferation and the AKT pathway
Time frame: 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.
Changes in pPRAS40, pGSK3b, Ki67
3 secondary outcomes
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
Time frame: 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
Time frame: 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
Time frame: 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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2017.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John FR Robertson, MD study chair
University of Nottingham
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AZD5363 in people with Invasive Breast Cancer, run by University of Nottingham at 11 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary endpoint: Pharmacodynamic biomarker analysis in tumour tissue to assess the biological effect of AZD5363 on markers of anti-proliferation and the AKT pathway (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2017.