Status:
COMPLETED
Study to Compare the Effects of AZD9496 vs Fulvestrant in Breast Cancer.
Lead Sponsor:
AstraZeneca
Conditions:
Postmenopausal Women With ER+ HER2- Primary Breast Cancer
Eligibility:
FEMALE
18-120 years
Phase:
PHASE1
Brief Summary
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 ...
Detailed Description
This is an open label, randomized, multi-centre study in postmenopausal women with primary ER+ HER2- breast cancer. Patients will be randomised to an oral dose of 250 mg bd AZD9496 or 500mg fulvestran...
Eligibility Criteria
Inclusion
- Inclusion criteria:
- Signed and dated informed consent form (ICF)
- Women \>=18 years
- Patients with newly diagnosed resectable primary breast cancer scheduled to undergo treatment with curative intent by surgery
- Histologically confirmed invasive breast cancer involving a palpable tumor of any size, or a tumor with an ultrasound assessed diameter of ≥ 1.0 cm
- Any clinical nodal status
- ER+breast cancer
- HER2- breast cancer defined as a negative in situ hybridization test or an immno-histochemistry (IHC) status of 0 or 1+
- Eastern Co-operative Oncology group (ECOG) performance status 0-1
- 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:
- Pre-treatment biopsy sample not likely to provide adequate tissue sections for the biomarker assays
- Previous systemic or local treatment for the new primary breast cancer currently under investigation (including surgery, radiotherapy, cytotoxic and endocrine treatments)
- Inflammatory breast cancer
- Evidence of metastases
- 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
- Concurrent treatment with other experimental drugs within 4 weeks prior to receiving study treatment
- Use of hormone-replacement therapy from \<4 weeks of the diagnostic/baseline core biopsy to the start of trial treatment
- Patients with second primary cancer. Any endocrine therapies or other anti-cancer therapies must have been ceased at least 12 months prior to enrollment.
- 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
- 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
- As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases,
- Uncontrolled symptomatic thyroid dysfunction (hyperthyroidism or hypothyroidism).
- Unexplained symptomatic endometrial disorders.
- 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.
- 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
- Direct involvement in the planning and conduct of the study
- History of hypersensitivity to AZD9496
- History of hypersensitivity to fulvestrant and/or castor oil
- 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
Exclusion
Key Trial Info
Start Date :
October 5 2017
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
February 12 2019
Estimated Enrollment :
49 Patients enrolled
Trial Details
Trial ID
NCT03236974
Start Date
October 5 2017
End Date
February 12 2019
Last Update
February 6 2020
Active Locations (12)
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1
Research Site
Erlangen, Germany, 91054
2
Research Site
Minden, Germany, 32429
3
Research Site
München, Germany, 81377
4
Research Site
Schwerin, Germany, 19049