Open-Label Umbrella Study To Evaluate Safety And Efficacy Of Elacestrant In Various Combination In Patients With Metastatic Breast Cancer
18 Years and older, Male and Female
STML-ELA-0222 (primary)
NCI-2023-02463
Summary
This is a multicenter, Phase 1b/2 trial. The phase 1b part of the trial aims to determine
the RP2D of elacestrant when administered in combination with alpelisib, everolimus,
palbociclib, abemaciclib, and ribociclib. The Phase 2 part of the trial will evaluate the
efficacy and safety of the various combinations in patients with ER+/HER2-
advanced/metastatic breast cancer.
Objectives
This is a multicenter, Phase 1b/2 trial. The Phase 1b aims at selecting the RP2D dose,
defined as a dose that is associated with less than 33% of patients experiencing a DLT of
elacestrant when administered in combination with alpelisib, everolimus, palbociclib,
abemaciclib, and ribociclib, that is, â?¤1 patient experiencing a DLT out of 6 DLT
evaluable patients. For each combination, this phase will have between 1 and 3 cohorts of
6 DLT-evaluable patients each. The total number of DLT-evaluable patients in all the
combinations will vary between 24 and 72.
The Phase 2 part of the trial will evaluate the efficacy and safety of the various
combinations in patients with ER+/HER2- advanced/metastatic breast cancer.
The treatment arms will be:
- Arm A: 50 patients: elacestrant with alpelisib;
- Arm B: 50 patients: elacestrant with everolimus;
- Arm C: 60 patients (30 patients in each combination): elacestrant with either
abemaciclib or ribociclib;
- Arm D: 90 patients (30 patients in each combination): elacestrant with either
palbociclib, abemaciclib, or ribociclib
- Arm E: 60 patients: elacestrant with capivasertib
Phase 1b will have a total of 90 patients, while Phase 2 will have 310 patients for all
treatment arm combinations.
Eligibility
- Patient has signed the informed consent before all study specific activities are conducted.
- Women or men aged â?¥18 years (or the minimum age of consent in accordance with the local law), at the time of informed consent signature. Female patients may be of any menopausal status.
- Postmenopausal status is defined by:
- Age â?¥60 years
- Age <60 years and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) or a follicle-stimulating hormone (FSH) value >40 mIU/mL and an estradiol value<40 pg/mL (140 pmol/L) or in postmenopausal ranges per local reference ranges
- Documentation of prior surgical sterilization (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, at least 1 month before first dose of trial therapy).
- Premenopausal and perimenopausal women (who do not fit postmenopausal criteria) and men must be concurrently receiving a luteinizing hormone-releasing hormone (LHRH) agonist initiated at least 4 weeks before the start of trial therapy and are planning to continue LHRH agonist treatment during the study treatment.
- For perimenopausal women to be considered of non-childbearing potential, FSH levels must be >40 mIU/ml.
- 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 â?¥10% of tumor cells demonstrate positive nuclear staining by immunohistochemistry, with or without PGR positivity. .
- At least 1 not previously irradiated measurable lesion as per RECIST version 1.1 and/or at least 1 lytic or mixed (lytic +sclerotic) bone lesion with identifiable soft tissue components meeting the definition of measurability by RECIST version 1.1 that can be evaluated by CT or MRI; patients with sclerotic/osteoblastic bone lesions only in the absence of measurable disease are not eligible.
- ECOG performance status of 0 or 1.
- Patient has adequate bone marrow and organ function, as defined by the following laboratory values:
- Absolute neutrophil count (ANC) â?¥1.5 Ã? 10^9/L
- Platelets â?¥100 Ã? 10^9/L
- Hemoglobin â?¥9.0 g/dL
- Potassium, sodium, calcium (corrected for serum albumin) and magnesium CTCAE grade â?¤1
- Creatinine is â?¤ 1.5 x ULN or if creatinine is > 1.5 x ULN, then creatinine clearance must be â?¥50 mL/min based on the Cockcroft-Gault formula. Note: C-G formula:
- Creatinine clearance (male) = ([140-age in years] Ã? weight in kg)/ ([serum creatinine in mg/dL] Ã? 72)
- Creatinine clearance (female) = (0.85 Ã? [140-age in years] Ã? weight in kg)/ ([serum creatinine in mg/dL] Ã? 72)
- Serum albumin â?¥3.0 g/dL (â?¥30 g/L)
- In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) â?¤ 3.0 Ã? ULN. If the patient has liver metastases, ALT and AST â?¤ 5 Ã? ULN
- Total serum bilirubin <1.5 Ã? ULN except for patients with Gilbert's syndrome who may be included if the total serum bilirubin is â?¤3.0 Ã? ULN or direct bilirubin â?¤ 1.5 Ã? ULN.
Treatment Sites in Georgia
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