The mammographic density reduction in healthy women
Conditions
Interventions
Product Name: (Z)-endoxifen
Pharmaceutical Form: Capsule
INN or Proposed INN: (Z)-Endoxifen
CAS Number: 112093-28-4
Other descriptive name: 4_[(Z)-1-[4-[2-(methylamino)ethoxy]phenyl]-2-phenylbut-1-eny
Sponsors
Atossa Therapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects 2.Attending the national mammography screening program. The screening mammogram should have been performed within 3 month of study inclusion. 3.Mammographic density assessed as BI-RADS® score B, C or D. 4.40-55 years old premenopausal women (defined as having at least one menstruation during the prior 12 months; women whose status is questionable in the mind of the PI will have an FSH test to confirm (FSH=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Any previous diagnosis of breast cancer, including carcinoma in situ, or any other cancer. Non-melanoma skin cancer and in situ cancer of the cervix are not exclusion criteria. 2.A history of breast surgery, e.g., reduction or enlargement, which might affect mammographic density measurements. 3.Mammographic BI-RADS® malignancy code =3 at baseline. 4.Previous treatment with an anti-oestrogen, including experimental drug studies (e.g., Karma CREME, Karisma-1 or Karisma-2). 5.A history of thromboembolic disease such as embolus, deep vein thrombosis, stroke, TIA (transient ischemic attack) or myocardial infarction. 6.Moderate hypertension at baseline defined as systolic pressure higher than 160 mm Hg or diastolic higher than 100 mm Hg. 7.BMI > 30. 8.Known APC (activated protein C) resistance, an inherited coagulation disorder. 9.Prescribed and regular use of anticoagulants (defined as substances included in group B01A in the ATC-system). 10.Allergy to endoxifen or any of its components. 11.Agents that have the potential to decrease endoxifen levels through increased metabolic clearance: a.Certain anti-epileptic therapies (carbamazepine, fenytoin, fenobarbital, lamotrigine) b.Certain antibiotics (rifamycins) c.St John’s wort (in Swedish: johannesört) d.Certain HIV medications (efavirenz, ritonavir) 12. Current, or within prior 6 months, use of hormone replacement therapy to treat menopausal symptoms 13. Women who have an increased risk of venous thrombosis due to immobilization, e.g., using wheelchair. 14.Uncontrolled diabetes (defined as HbA1c >50 mmol/mol). 15.Cataract. 16.Pregnant or plan to become pregnant in the next year. 17.Lactating. 18.Not able to understand the study information and/or informed consent. 19.Participation in another investigational clinical trial in the last 6 months. 20.Any reason for which the investigator considers the patient is not suitable for the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the dose-response relationship of daily oral (Z) endoxifen by measurement of mammographic breast density area (cm2) reduction.;Secondary Objective: The secondary objective of this study is to assess the safety and tolerability of daily oral (Z)-endoxifen. The exploratory objectives of this study are: -To determine if daily oral (Z)-endoxifen for a maximum of six months results in at least a one category reduction in the BI-RADS® scale -To determine the durability of (Z)-endoxifen on breast density response at 24 months post standard of care screening mammogram (difference between end of treatment and 24-month breast density) -To evaluate the levels of endoxifen over time and correlate endoxifen values to density change ;Primary end point(s): Change of mammographic density area (cm2) assessed by iCAD® software after 6 months of daily (Z) endoxifen treatment. ;Timepoint(s) of evaluation of this end point: 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change from baseline of safety and tolerability of daily oral (Z)-endoxifen by subject responses to the BCPT Eight Symptom Scale (BESS) questionnaire and AE collection. Clinical assessment, laboratory tests, and participant responses to questionnaires. Change from baseline on the BI-RADS® scale assessed by iCAD® software after 3 and 6 months of daily (Z)-endoxifen treatment. Exploratory endpoints: Reduction of at least one category on the BI-RADS® scale assessed by both iCAD® and Stratus software after a maximum of 6 months of daily (Z)-endoxifen treatment. Durability of breast density response at 24 months post standard of care screening mammogram (difference between end of treatment and 24-month breast density). ;Timepoint(s) of evaluation of this end point: 3, 6 months | — |
Countries
Sweden
Contacts
Public ContactHeather Fraser, VP Clinical
Atossa Therapeutics Inc.
Outcome results
None listed