Locally Advanced or Metastatic ER+/HER2- Breast Cancer with an ESR1 Mutation MedDRA version: 21.1 Level: LLT Classification code 10072737 Term: Advanced breast cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: Lasofoxifene
Pharmaceutical Form: Tablet
INN or Proposed INN: LASOFOXIFENE TARTRATE
CAS Number: 190791-29-8
Other descriptive name: LASOFOXIFENE TARTRATE
Concentration unit: mg milligram
Sponsors
Sermonix Pharmaceuticals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Pre- or postmenopausal. Postmenopausal women are defined as: a. >=60 years of age with no vaginal bleeding over the prior year, or b. =1,500 cells/mm3 b. platelet count >=100,000 cells/mm3 c. hemoglobin >=9.0 g/dl d. ALT and AST levels =2.5 upper limit of normal (ULN) or <5 in the presence of visceral metastasis e. total serum bilirubin =1.5 X ULN (=3.0 X ULN for subjects known to have Gilbert Syndrome) f. alkaline phosphatase level <2.5 X ULN g. creatinine clearance of 40 ml/min or greater as calculated by the Cockcroft-Gault formula h. international normalized ratio (INR) and activated partial thromboplastin (aPTT) <2.0 X ULN. 9. Able to swallow tablets. 10. Able to understand and voluntarily sign a written informed consent before any screening procedures. Are the trial subjects under 18? no Numbe
Exclusion criteria
Exclusion criteria: 1. Prior use of everolimus or other mammalian target of rapamycin (mTOR) inhibitor phosphoinositide 3-kinase inhibitor (PI3K) inhibitors are excluded unless discontinued due to reasons other than disease progression. 2. Presence of brain metastasis. 3. Lymphangitic carcinomatosis involving the lung. 4. Impending visceral crisis in need of cytotoxic chemotherapy as assessed by the investigator. 5. Radiotherapy within 30 days prior to randomization except in case of localized radiotherapy for analgesic purposes or for lytic lesions at risk of fracture, which can then be completed within 7 days prior to randomization. Subjects must have recovered from radiotherapy toxicities prior to randomization. 6. History of long QTC syndrome or a QTC of >480 msec. 7. History of a pulmonary embolus (PE) or deep vein thrombosis (DVT) within the last 6 months or any known thrombophilia. Subjects stable on anti-coagulants for maintenance are eligible as long as the DVT and/or PE occurred >6 months prior to enrollment and there is no evidence for active thrombosis. The use of low dose acetylsalicylic acid (ASA) is permitted. 8. Any significant co-morbidity that would impact the study or the subject’s safety. 9. History of a positive human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) at Screening. Subjects cured of hepatitis C (no viral load) are eligible. 10. History of malignancy within the past 5 years (excluding breast cancer), except basal cell or squamous cell carcinoma of the skin curatively treated by surgery, or early stage cervical cancer. 11. History of vaginal bleeding over the last year unless it is documented that the bleeding was due to non-uterine causes (e.g. vaginal atrophy). Premenopausal women on ovarian suppression with breakthrough bleeding can be enrolled in the study 12. Uncontrolled hypertension defined as sitting systolic pressure >160 mm Hg or diastolic pressure >100 mm Hg at Screening. 13. History of non-compliance to medical regimens. 14. Unwilling or unable to comply with the protocol. 15. Current participation in any clinical research trial involving an investigational drug or device within the last 30 days.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the progression free survival (PFS) of 5 mg lasofoxifene relative to fulvestrant for the treatment of pre- and postmenopausal women with locally advanced or metastatic estrogen receptor positive (ER+)/human epidermal growth factor 2 negative (HER2-) breast cancer with an estrogen receptor 1 (ESR1) mutation.;Secondary Objective: Evaluate: • Clinical benefit rate (CBR) • Objective Response Rate (ORR) • Duration of response • Time to response • Overall Survival (OS) • Pharmacokinetics of lasofoxifene • Quality of Life (QoL): vaginal assessment scale (VAS) and vulvar assessment scale (VuAS) questionnaires • Safety of lasofoxifene • Response to various ESR1 mutation subtypes (Y537S, Y537C, D538G, E380Q, S463P, V534E, P535H, L536H, L536P, L536R, L536Q, or Y537N) ;Primary end point(s): Progression-Free Survival (PFS): • PFS is defined as the interval from the date of randomization to the earlier date of first documented radiographic progression or death due to any cause ;Timepoint(s) of evaluation of this end point: Radiographic assessment every 8 weeks until disease progression | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary objectives of the study are to evaluate: • Clinical benefit rate (CBR) • Objective Response Rate (ORR) • Duration of response • Time to response • Overall Survival (OS) • Pharmacokinetics of lasofoxifene • Quality of Life (QoL): vaginal assessment scale (VAS) and vulvar assessment scale (VuAS) questionnaires • Safety of lasofoxifene • Response to various ESR1 mutation subtypes (Y537S, Y537C, D538G, E380Q, S463P, V534E, P535H, L536H, L536P, L536R, L536Q, or Y537N) ;Timepoint(s) of evaluation of this end point: 1. The ESR1 mutation assessments will be done at Screening visit, Visit 3 (Week 8) and Final/ET Visit. 2. Serum samples for Lasofoxifene PK will be collected at each visit until Final/ET visit. 3. ECGs will be performed at Screening, at the end of 1, 6, and 12 months of treatment, at the Final/ET visit. 4. Hematology, blood chemistry, coagulation tests will be performed at each visit until Final/ET visit. 5. Physical examinations, a brief neurological examination, and body weight measurement will be done at every visit. 6. Adverse events assessment will be recorded at each visit until Final/ET visit. | — |
Countries
Canada, Czechia, Israel, Lithuania, United States
Contacts
Public ContactClinical Trials Information
Sermonix Pharmaceuticals
Outcome results
None listed