Postmenopausal Women With ER+ HER2- Primary Breast Cancer Clinical Trial
— D6090C00002Official title:
An Open Label, Randomised, Pre-surgical, Pharmacodynamics Study to Compare the Biological Effects of AZD9496 Versus Fulvestrant in Postmenopausal Women With ER Positive HER-2 Negative Primary Breast Cancer
| Verified date | February 2020 |
| Source | AstraZeneca |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This is an open label randomised multicentre pre-surgical pharmacodynamics study to compare
and assess the biological effects of AZD9496 and fulvestrant in postmenopausal women with
estrogen receptor (ER) positive (ER+), human epidermal growth factor receptor 2 (HER-2)
negative (HER2-) primary breast cancer.
Patients will receive AZD9496 or fulvestrant and will have an on-treatment image
-guided core biopsy after 5-14 days of commencing treatment.
| Status | Completed |
| Enrollment | 49 |
| Est. completion date | February 12, 2019 |
| Est. primary completion date | February 12, 2019 |
| Accepts healthy volunteers | No |
| Gender | Female |
| Age group | 18 Years to 120 Years |
| Eligibility |
Inclusion criteria: 1. Signed and dated informed consent form (ICF) 2. Women >=18 years 3. Patients with newly diagnosed resectable primary breast cancer scheduled to undergo treatment with curative intent by surgery 4. Histologically confirmed invasive breast cancer involving a palpable tumor of any size, or a tumor with an ultrasound assessed diameter of = 1.0 cm 5. Any clinical nodal status 6. ER+breast cancer 7. HER2- breast cancer defined as a negative in situ hybridization test or an immno-histochemistry (IHC) status of 0 or 1+ 8. Eastern Co-operative Oncology group (ECOG) performance status 0-1 9. Post-menopausal status defined as meeting at least one of the following criteria: Have undergone a bilateral oophorectomy; Age =60 years; Age =50 years and with cessation of regular menses =12 months and with an intact uterus in the absence of oral contraception or hormone-replacement therapy (HRT) prior to the diagnosis of breast cancer; Age <60 years and with cessation of regular menses =12 months and follicle stimulating hormone (FSH) and oestradiol levels in the postmenopausal range Exclusion criteria: 1. Pre-treatment biopsy sample not likely to provide adequate tissue sections for the biomarker assays 2. Previous systemic or local treatment for the new primary breast cancer currently under investigation (including surgery, radiotherapy, cytotoxic and endocrine treatments) 3. Inflammatory breast cancer 4. Evidence of metastases 5. Patients currently receiving medications or herbal supplements known to be strong inhibitors/inducers of CYP3A4/5 or strong inhibitors of CYP2C8 or that are sensitive substrates of CYP2C8 inhibition 6. Concurrent treatment with other experimental drugs within 4 weeks prior to receiving study treatment 7. Use of hormone-replacement therapy from <4 weeks of the diagnostic/baseline core biopsy to the start of trial treatment 8. Patients with second primary cancer. Any endocrine therapies or other anti-cancer therapies must have been ceased at least 12 months prior to enrollment. 9. Any of the following cardiac criteria: - Mean resting QT interval corrected for heart rate (QTc) > 470 msec obtained from 3 ECGs using Fridericia's formula - 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 10. Experience of any of the following in the preceding 6 months: coronary artery bypass graft (CABG), angioplasty, vascular stent, myocardial infarction (MI), angina pectoris, congestive heart failure New York Heart Association (NYHA) Grade =2, cerebrovascular accident (CVA), transient ischaemic attack (TIA), deep venous or arterial thrombosis, pulmonary embolism, bleeding diathesis (i.e., disseminated intravascular coagulation, clotting factor deficiency) or requirement of anticoagulant therapy 11. As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, 12. Uncontrolled symptomatic thyroid dysfunction (hyperthyroidism or hypothyroidism). 13. Unexplained symptomatic endometrial disorders. 14. Refractory nausea and vomiting, uncontrolled chronic GI diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD9496. 15. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: absolute neutrophil count < 1.5 x 109/L, Platelet count < 100 x 109/L, Haemoglobin < 90 g/L, alanine aminotransferase (ALT) > 2.5x upper limit of normal (ULN), aspartate aminotransferase (AST) > 2.5 x ULN, Total bilirubin > 1.5 x ULN or > 3 x in case of Gilbert's Syndrome, glomerular filtration rate < 50 mL/min 16. Direct involvement in the planning and conduct of the study 17. History of hypersensitivity to AZD9496 18. History of hypersensitivity to fulvestrant and/or castor oil 19. Judgment by the investigator that the patient should not participate in the study if unlikely to comply with study procedures, restrictions and requirements In addition, the following is considered a criterion for exclusion from the exploratory genetic research: Previous allogeneic bone marrow transplant; Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection |
| Country | Name | City | State |
|---|---|---|---|
| Germany | Research Site | Erlangen | |
| Germany | Research Site | Minden | |
| Germany | Research Site | München | |
| Germany | Research Site | Schwerin | |
| United Kingdom | Research Site | Derby | |
| United Kingdom | Research Site | Edinburgh | |
| United Kingdom | Research Site | London | |
| United Kingdom | Research Site | London | |
| United Kingdom | Research Site | London | |
| United Kingdom | Research Site | Manchester | |
| United Kingdom | Research Site | Poole | |
| United Kingdom | Research Site | Sutton In Ashfield |
| Lead Sponsor | Collaborator |
|---|---|
| AstraZeneca |
Germany, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Pharmacodynamics changes to estrogen receptor (ER) expression following treatment with AZD9496 or fulvestrant | Evaluation of AZD9496 and fulvestrant activity in the tumour by assessment of pharmacodynamics biomarker changes i.e. ER expression | Tumour biopsy taken at baseline within 6 weeks of planned start of study treatment; on-treatment tumour biopsy taken following 5-14 day on study treatment | |
| Secondary | Pharmacodynamics changes to progesterone receptor (PgR) expression following treatment with AZD9496 or fulvestrant | Evaluation of AZD9496 and fulvestrant activity in the tumour by assessment of pharmacodynamics biomarker changes i.e. PgR expression | Tumour biopsy taken at baseline within 6 weeks of planned start of study treatment; on-treatment tumour biopsy taken following 5-14 day on study treatment | |
| Secondary | Pharmacodynamics changes to Ki67 protein biomarker expression following treatment with AZD9496 or fulvestrant | Evaluation of AZD9496 and fulvestrant activity in the tumour by assessment of pharmacodynamics biomarker changes i.e. Ki67 protein biomarker expression | Tumour biopsy taken at baseline within 6 weeks of planned start of study treatment; on-treatment tumour biopsy taken following 5-14 day on study treatment | |
| Secondary | Safety and tolerability of AZD9496 | Safety and tolerability will be assessed in terms of adverse events (AEs), laboratory data, vital signs and ECG changes. | From first dose until 28 days after last dose of AZD9496 | |
| Secondary | Safety and tolerability of fulvestrant | Safety and tolerability will be assessed in terms of adverse events (AEs), laboratory data and vital signs | From first dose until 28 days after fulvestrant | |
| Secondary | Plasma concentration of AZD9496 - stand alone biopsy visit option | Determination of AZD9496 concentrations in plasma | Blood samples collected close as possible to time of biopsy, 1-2 hours after biopsy and optional 3-4 hours after biopsy | |
| Secondary | Plasma concentration of fulvestrant | Determination of fulvestrant concentration in plasma | A blood sample will be collected anytime before biopsy. | |
| Secondary | Plasma concentration of AZD9496 - on the table biopsy option | Determination of AZD9496 concentration in plasma | Blood samples collected close as possible to time of biopsy, at least 2 hours after biopsy and 8-12 hours after last dose or at discharge which is defined as up to 12 hours after last dose |