Overview

AKT Inhibitor in Oestrogen Positive Breast Cancer

Status:
Completed
Trial end date:
2017-02-21
Target enrollment:
0
Participant gender:
Female
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
University of Nottingham
Collaborators:
AstraZeneca
Cancer Research UK
National Cancer Research Network
Treatments:
Estrogens
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