Exploratory Study to Assess the Short Term Intratumoural and Peripheral Effects of BN83495 in Postmenopausal Women With Newly Diagnosed Breast Cancer

Study Overview
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Brief Summary
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This trial will assess the intratumoural pharmacological activity of BN83495 by changes in intratumoural levels of sex hormones and associated inhibition of steroid sulphatase (STS) activity.

Official Title
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A Phase II, Open-label, Exploratory Study to Assess the Short Term Intratumoural and Peripheral Effects of BN83495 Administered for 14 Days Prior to Surgery to Postmenopausal Women With Newly Diagnosed Primary Invasive Oestrogen Receptor Positive Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: BN83495


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female subjects 55 to 80 years with histologically or cytologically documented primary intraductal or lobular invasive breast cancer that meets the following criteria: T2, N0 or N1, M0. Primary tumour clinically determined to be 2 to 5 cm in the greatest dimension. Laboratory documentation of positive oestrogen receptor (ER+) status in at least 10% of the tumour cells. Laboratory documentation of HER-2 negative status. Postmenopausal defined as no spontaneous menses for a total of 2 years amenorrheic for at least 12 months with serum oestrogen level <30 pg/mL, and both luteinising hormone (LH)/follicle stimulating hormone (FSH) >20 IU/L, chemotherapy-induced amenorrhoea for at least 12 months bilateral oophorectomy, or radiation castration and amenorrhoeic for at least 3 months. Eastern Cooperative Oncology Group (ECOG) performance status ≤2. Exclusion Criteria: Has locally advanced breast cancer that is considered non-operable without neoadjuvant therapy. Has evidence of metastatic disease as a diagnosis of inflammatory breast cancer Has ductal carcinoma in situ

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BN83495<br>40mg tablet oral daily administration from Day 1 to Day 14. | Drug: BN83495<br>* 40mg tablet oral daily administration from Day 1 to Day 14.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intratumoural levels of sex hormones |  | Baseline and Day 14 | 
| Intratumoural steroid sulphatase activity |  | Baseline and Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the intratumoural Ki67 proliferation index |  | Baseline and Day 14 | 
| Proportion of subjects with a decrease in Ki67 staining ≥50% |  | Baseline and Day 14 | 
| Proportion of subjects with complete cell cycle response, defined as Ki67 staining ≤1% |  | Baseline and Day 14 | 
| Change in Apoptotic Index determined by M30 antibody |  | Baseline and Day 14 | 
| Change in Growth Index (Ki67 proliferation index/M30 apoptotic index) |  | Baseline and Day 14 | 
| Change in steroid sulphatase activity in peripheral blood mononuclear cells (PBMCs). |  | Baseline and Day 14 |