ELACESTRANTin Women and Men with CDK4/6 Inhibitor-Naive Estrogen Receptor Positive, HER-2 Negative Metastatic Breast Cancer: An Open-Label Multicenter Phase 2 Study (ELCIn)
- Conditions
- metastatic breast cancerMedDRA version: 20.0Level: LLTClassification code: 10027475Term: Metastatic breast cancer Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-503214-68-00
- Lead Sponsor
- Stemline Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 80
Patient has signed the informed consent before all study-specific activities are conducted., Women or men aged =18 years (or the minimum age of consent as per local law), at the time of informed consent signature. ? Female patients may be either postmenopausal or premenopausal/perimenopausal. o Postmenopausal status is defined by: - Age =60 years - Age <60 years and amenorrhea for 12 or more months (without an alternative cause) and follicle-stimulating hormone (FSH) value and estradiol level within the local laboratory reference range for postmenopausal female patients. - Documentation of prior bilateral oophorectomy, at least 1 month before first dose of trial therapy. ? Premenopausal or perimenopausal women and men must be concurrently given a luteinizing hormone-releasing hormone (LHRH) agonist starting at least 3 to 4 weeks before the start of trial therapy and is planning to continue LHRH during the study., Documentation of histopathological or cytological confirmed ER+/HER2–breast cancer, per local laboratory, as per the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines (Allison et al, 2020, Wolff et al, 2018). Note: In the context of this trial, ER status will be considered positive if =10% of tumor cells demonstrate positive nuclear staining by immunohistochemistry, with or without PgR positivity., At least 1 measurable lesion as per RECIST version 1.1 or a mainly lytic bone lesion for bone disease only., ECOG performance status of 0 or 1., Patient has adequate bone marrow and organ function, as defined by the following laboratory values: a. Absolute neutrophil count (ANC) =1.5 × 109/L b. Platelets =100 × 109/L c. Hemoglobin =9.0 g/dL d. Sodium, potassium, calcium (corrected for serum albumin), magnesium, blood urea nitrogen (BUN), chloride, and total blood CO2 CTCAE v5.0 grade =1 e. Cockcroft-Gault based creatinine clearance =50 mL/min. Note: o Creatinine clearance (male) = ([140-age in years] × weight in kg)/ ([serum creatinine in mg/dL] × 72) Stemline Therapeutics, Inc. Protocol STML-ELA-0322 Clinical Study Protocol 2.0 15 June 2023 Confidential Page 34 of 90 o Creatinine clearance (female) = (0.85 × [140-age in years] × weight in kg)/ ([serum creatinine in mg/dL] × 72) f. Serum albumin =3.0 g/dL (=30 g/L) g. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =3.0 × upper limit of normal (ULN) in the absence of liver metastasis. h. If the patient has liver metastases, ALT, and AST =5.0 × ULN i. Total serum bilirubin <1.5 × ULN except for patients with Gilbert’s syndrome who may be included if the total serum bilirubin is =3.0 × ULN or direct bilirubin = 1.5 × ULN. Note: Laboratory assessments may be repeated once during the Screening Phase after supplementation or transfusions., The patient is able and willing to comply with study protocol requirements., Patient has received at least 1 (and up to 2) prior hormonal therapy in the advanced/metastatic setting.
Active or newly diagnosed central nervous system (CNS) metastases, including meningeal carcinomatosis. Note: Patients with stable brain metastases are allowed, only if the patient has completed local therapy and is on a stable or decreasing dose of corticosteroids (= 2.0 mg/day of dexamethasone or equivalent) for at least 4 weeks before starting treatment in this study. In addition, any signs (e.g., radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment., Men who do not agree to abstain from donating sperm, or to use a highly effective method of contraception within 28 days of the first dose of study treatment through 120 days after the last dose of study treatment. For subjects (who have not undergone vasectomy) with female partners of childbearing potential, the subject and his partner must use highly effective methods of contraception, as described in Appendix E., Females who are pregnant or breastfeeding. Females should not get pregnant during study treatment and for 120 days after last dose of study treatment. Females should not breastfeed during administration of elacestrant and for 1 week after receiving the last dose., Patient is currently receiving or received any of the following medications prior to first dose of trial therapy: o Any anti-cancer therapy within 14 days (28 days in case of anticancer antibody-based treatments) or 5 half-lives, whichever is shorter. o Fulvestrant treatment (last injection) <42 days before first dose of study drug o Any other endocrine therapy <14 days or 5 half-lives, whichever is shorter, before first dose of study drug o Known strong or moderate inducers or inhibitors of cytochrome P450 (CYP) 3A4 within 14 days or 5 half-lives, whichever is shorter, (Refer to Section 5.7.3), o Herbal preparations/medications within 7 days. These include, but are not limited to, St. John’s wort, kava, ephedra (ma huang), ginkgo biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng, Any severe medical or psychiatric condition that in the opinion of the investigator(s) would preclude the patient’s participation in a clinical study., Patients with visceral crisis who are at risk of life-threatening complications in the short term, including but not limited to: massive uncontrolled effusions (peritoneal, pleural, pericardial) and liver involvement of >50%., Prior treatment with chemotherapy, CDK4/6i (including adjuvant), elacestrant, other investigational selective estrogen receptor degraders (SERDs) or alike agents such as selective estrogen receptor modulators (SERMs), selective estrogen receptor covalent antagonists (SERCANs), complete estrogen receptor antagonists (CERANs), and proteolysis-targeting chimeras (PROTACs), in the advanced/metastatic setting., Patient has a concurrent malignancy or history of invasive malignancy within 3 years of enrollment, with the exception of basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix that has completed curative treatment., Uncontrolled significant active infections. ? Patients with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection must have undetectable viral load during screening. ? Patients known to be HIV+ are allowed if they have undetectable viral load at baseline., Major surgery or radiotherapy within 28 days before starting trial therapy., Inability to take oral medication, refractory or chronic nausea, gastrointestinal condi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Evaluate the efficacy of elacestrant in patients with ER+/HER2– advanced/metastatic breast cancer who received 1 or 2 prior hormonal therapy in the metastatic setting and no prior CDK4/6i;Secondary Objective: • Evaluate other efficacy measures of elacestrant • Evaluate the quality of life of patients receiving elacestrant • Further characterize the safety of elacestrant;Primary end point(s): Progression Free Survival (PFS) rate at 6 months, as per investigator’s assessment
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Objective Response Rate (ORR): proportion of patients who achieve a best overall response (BOR) of partial response (PR) or complete response (CR) Duration of Response (DoR): time from the date of first documented CR/PR until the first radiological documentation of disease progression or death, whichever comes first Clinical Benefit Rate (CBR) over 24 weeks: proportion of patients who achieve a BOR of SD, PR or CR over 24 weeks Progression Free Survival (PFS) Overall Survival (OS)