Trial Title:
Elacestrant With/Without Triptorelin in Premenopausal Women With Luminal Breast Cancer
NCT ID:
NCT05982093
Condition:
Breast Cancer
HER2-negative Breast Cancer
Hormone Receptor Positive Tumor
Premenopausal Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Triptorelin Pamoate
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
parallel, non-comparative, two-arm, randomized 1:1, open-label, multicenter, exploratory
window of opportunity study
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Elacestrant
Description:
Elacestrant 400 mg given orally on a daily and continuous basis for 30 days or until the
day before surgery or biopsy (+7 extra days).
Arm group label:
Elacestrant
Arm group label:
Elacestrant + Triptorelin
Other name:
Orserdu
Intervention type:
Drug
Intervention name:
Triptorelin
Description:
Monthly triptorelin 3.75 mg powder and solvent for prolonged-release suspension for
injection. Each vial contains 3.75 mg of triptorelin (acetate). After reconstitution with
2 ml of solvent, 1 ml of the suspension contains 1.875 mg triptorelin. This drug contains
sodium, but less than 1 mmol (23 mg) of sodium per vial.Triptorelin will be administrated
on D1 and D29.
Arm group label:
Elacestrant + Triptorelin
Other name:
Orserdu
Summary:
PREMIERE parallel, non-comparative, two-arm, randomized 1:1, open-label, multicenter,
exploratory window of opportunity study in premenopausal women with primary operable
HR+/HER2-negative breast cancer with aiming at evaluating the biological effects of
elacestrant with or without triptorelin.
Detailed description:
PremiÈRe is a 4-week preoperative WOO randomized 2-arms study with a full program in
correlative science, including an accurate estradiol measurement to evaluate the efficacy
and biological activity of elacestrant in premenopausal patients with and without OFS
(elacestrant 400mg per day during 28 days vs elacestrant at 400 mg per day during 28 days
plus triptorelin 3.75mg i.m). Biological information (by tumor biopsy and /or blood
sample) will be obtained at baseline, on day 14 (only blood) and day 28 post-treatment.
Endpoints as rate of CCCA, mean reduction of Ki67 and estrogen-sensitive signature,
allowing comparison of elacestrant activity across populations with and without OFS.
Regarding the main objective, rate of CCCA, and considering the eligible population (ki67
between 10-35%) and unpublished data from ELIPSE study we estimate around a 20% of CCCA
in all randomized patients. It's worthy to mention that a study using triptorelin as GnRH
analog and GCMSMS for E2 measurement showed that nearly all women at day 14 (24 of out
26) had E2 levels in the postmenopausal range26, allowing us to compare groups with and
without OFS at that early time-point.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Signed informed consent must be obtained prior to any trial-specific procedure.
2. Female patients who are at least 35 years of age on the day of signing informed
consent.
3. Patient is premenopausal at the time of study entry
Premenopausal status is defined as either:
- Patient had last menstrual period within the last 6 months. OR
- Plasma estradiol and FSH in the premenopausal range, according to local
laboratory definition.
Note: Patients who have undergone bilateral oophorectomy are not eligible.
4. Histologically confirmed non-metastatic primary invasive adenocarcinoma of the
breast untreated and recently diagnosed, with all the following characteristics:
- Stage I to stage IIB operable breast cancer (7th Edition of the AJCC). Note:
Axillary lymph node status must be assessed by fine needle biopsy or core
biopsy. This procedure at screening will be omitted if there is no suspicion
for positive axillary lymph node(s) radiographically or if a pathological
report of suspicious lymph nodes of the results of a fine needle biopsy or core
biopsy is available prior to the screening period.
- Absence of distant metastasis (i.e., M0) as determined by institutional
practice.
- At least 1 lesion that can be accurately and serially measured in at least 1
dimension and for which the longest diameter is ≥ 10 mm as measured by magnetic
resonance imaging (MRI) or ultrasound (US).
- In the case of a multifocal tumor, the largest lesion must be ≥ 10 mm and
designated the "target" lesion for all subsequent tumor evaluations. All
biopsied tumors had to be ER+HER2-negative
5. ER-positive with expression higher than 10% and HER2-negative tumor
- HER2 negativity is defined as either of the following: Immunohistochemistry
(IHC) 0, IHC 1+ or IHC2+/in situ hybridization (ISH) negative as per most
recent American Society of Clinical Oncology (ASCO)-College of American
Pathologists Guideline (CAP) guideline according to the local laboratory as
determined on the most recently analyzed tissue sample.
- Documentation of ER positive tumor with ≥ 10% staining by immunohistochemistry
of cells as per most recent ASCO-CAP guideline according to the local
laboratory determined on the most recently analyzed tissue sample, with or
without progesterone receptor positivity.
6. Ki67 expression ≥ 10% and ≤ 35% by local assessment
7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
8. Breast cancer eligible for primary surgery.
9. Availability of pre-treatment tumor tissue sample of FFPE tumor block from primary
tumor for biomarker analysis. The tumor tissue should be of good quality based on
total and viable tumor content and must be evaluated centrally for quality prior to
enrollment. Archival tumor tissue or ex professo biopsy are acceptable.
10. Adequate hematologic and organ function within 14 days before the first study
treatment on Day 1, defined by the following:
1. Neutrophils (ANC ≥1.000/μL).
2. Hemoglobin ≥ 9.0 g/dL (with no need for transfusions).
3. Platelet count ≥ 75. 000/μL.
4. Serum creatinine ≤1.5 mg/dL or calculated creatinine clearance ≥30 mL/min
(Cockcroft-Gault Equation)
5. International normalized ratio (INR) or prothrombin time (PT) ≤1.5 × ULN and
activated partial thromboplastin time (aPTT) within therapeutic range.
Note: Subjects who are receiving anticoagulation treatment which is monitored
by INR (eg, warfarin) may be allowed to participate if they have a stable INR
(ie, within therapeutic range) for at least 28 days prior to the first dose of
study drug, in the absence of any exclusionary medical conditions, and provided
that elacestrant would be appropriate therapy for the subject
6. Potassium, total Calcium (corrected for serum albumin), and sodium NCI CTCAE
v5.0 Grade ≤ 1.
7. Alanine aminotransferase (ALT) ≤ 3x upper limit of normal (ULN)
8. Aspartate aminotransferase (AST) ≤ 3x ULN
9. Total bilirubin ≤ ULN or total bilirubin ≤ 1.5x ULN with direct bilirubin ≤ ULN
of the laboratory in subjects with documented Gilbert's Syndrome
11. Patient must be willing and able to comply with scheduled visits, treatment plans,
laboratory tests, and other trial procedures.
12. Women of childbearing potential (CBP), defined as all women physiologically capable
of becoming pregnant, must have confirmed negative serum pregnancy test within 7
days prior to randomization.
13. Female subjects must not donate, or retrieve for their own use, oocytes from the
time of screening and throughout the study treatment period, and for at least 120
days after the time of final study drug administration.
14. Women of CBP must be willing to use highly effective methods of contraception.
Contraception must continue during the trial treatment and after stopping the
treatment received according to protocol. Highly effective contraception methods
include:
- Total abstinence (when this is in line with the preferred and usual lifestyle
of the patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of
contraception.
- Placement of a non-hormonal intrauterine device (IUD). Notes: Use of oral
(estrogen and progesterone), transdermal, injected, implanted, hormone
containing intrauterine system, or any other hormonal methods of contraception
is not allowed in this trial. Women are considered of CBP unless: they have had
≥ 12 months of natural (spontaneous) amenorrhea with an appropriate clinical
profile (i.e., age-appropriate history of vasomotor symptoms) or have had
surgical bilateral oophorectomy (with or without hysterectomy), total
hysterectomy, or tubal ligation at least four weeks prior to randomization. In
the case of oophorectomy alone, only when the reproductive status of the woman
has been confirmed by follow-up hormone level assessment, she will be
considered not of CBP. After the end of trial treatment, patients should use
effective contraception at least until 28 days after therapy discontinuation.
15. Patients must have the ability to swallow oral medication.
Exclusion Criteria:
1. Inoperable locally advanced or inflammatory breast cancer (any stage III).
2. Metastatic (Stage IV) breast cancer.
3. Synchronous invasive bilateral or multicentric breast cancer.
4. Patients requiring immediate neoadjuvant chemotherapy or immediate surgical
intervention.
5. Patients who have undergone sentinel lymph node biopsy or tumor excisional biopsy
prior to study treatment.
6. Prior malignancy within 3 years prior to randomization, except curatively treated
non-melanoma skin cancer, in situ cancer or adequately and curatively treated Stage
I or II cancer from which the patient is currently in complete remission.
7. Patients currently on following medications, which cannot be interrupted 7 days
prior treatment start:
- Any prohibited medication as per decapeptyl (triptorelin) label
- Strong inhibitors of CYP3A4, including grapefruit, grapefruit hybrids,
pummelos, starfruit and Seville oranges
- Known strong or moderate inducers or inhibitors of cytochrome P450 (CYP) 3A4
(Refer to http://medicine.iupui.edu/clinpharm/ddis/) within 5 half-life of the
drug prior to initiating trial therapy
- Herbal preparations/medications. These include, but are not limited to, St.
John's wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone
(DHEA), yohimbe, saw palmetto, and ginseng within 5 half-life of the drug prior
to initiating trial therapy
- Vaccination, including but not limited to vaccination against COVID-19, during
the 7 days prior to randomization.
8. Any treatment, local or systemic, including prior chemotherapy, ET, targeted
therapy, and/or radiation therapy for the currently diagnosed BC prior to
enrollment.
9. Major surgical procedure or significant traumatic injury within 28 days prior to
randomization.
10. Assessment by the investigator to be unable or unwilling to comply with the
requirements of the protocol.
11. Any of the following within 6 months before enrollment: myocardial infarction,
severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE v5.0 Grade ≥ 2,
prolonged QTcF ≥ Grade 2 (i.e., > 480 msec), uncontrolled atrial fibrillation of any
grade, coronary/peripheral artery bypass graft, heart failure ≥ Class II as defined
by the New York Heart Association guidelines, or cerebrovascular accident including
transient ischemic attack.
12. Child-Pugh Score greater than Class A (i.e., score >6)
13. Coagulopathy or any history of coagulopathy within the past 6 months, including
history of deep vein thrombosis or pulmonary embolism. However, subjects with the
following conditions will be allowed to participate:
1. Adequately treated catheter-related venous thrombosis occurring >28 days prior
to the first dose of study drug
2. Treatment with an anticoagulant, e.g., warfarin or heparin, for a thrombotic
event occurring > 6 months before enrollment, or for an otherwise stable and
allowed medical condition (eg, well controlled atrial fibrillation), provided
dose and coagulation parameters (as defined by local standard of care) are in
therapeutic range prior to the first dose of study drug and provided that an AI
would be an appropriate therapy for the subject
14. Known hypersensitivity to any of the study drugs, including excipients.
15. Known difficulty in tolerating oral medications or conditions which would impair
absorption of oral medications such as: uncontrolled nausea or vomiting (i.e., CTCAE
≥ Grade 3 despite antiemetic therapy), ongoing gastrointestinal obstruction/motility
disorder, malabsorption syndrome, or prior gastric bypass.
16. History of or clinical evidence of significant co-morbidities that, in the judgment
of the investigator, may interfere with the conduction of the study, the evaluation
of response, or with informed consent.
17. Previous hormonal treatments for other indications such as osteoporosis, breast
cancer prevention, hormonal substitutive therapy, such as raloxifene, tamoxifen,
estrogen, progestins must have ended at least 12 months prior to trial registration.
If a patient is on natural products known to contain progestins, they must be
stopped 14 days prior to beginning study treatment.
18. Used any prescription medication during the prior 1 month that the investigator
judge is likely to interfere with the study or to pose an additional risk to the
patient in participating.
19. Female subject who is pregnant or breastfeeding or intends to become pregnant during
the study.
Gender:
Female
Minimum age:
35 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Hospital Universitario Virgen de la Arrixaca
Address:
City:
El Palmar
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Ana Pérez
Email:
dm.oncoarrixaca@gmail.com
Investigator:
Last name:
Pilar Sánchez
Email:
Principal Investigator
Facility:
Name:
Hospital Universitari Vall d'Hebron
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Meritxell Bellet
Investigator:
Last name:
Meritxell Bellet
Email:
Principal Investigator
Facility:
Name:
Hospital Clinic de Barcelona
Address:
City:
Barcelona
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Maria Vidal, MD
Facility:
Name:
Complejo Hospitalario San Pedro de Alcántara
Address:
City:
Cáceres
Zip:
10003
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Santiago González, MD
Facility:
Name:
Hospital Universitario 12 de Octubre
Address:
City:
Madrid
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Pablo Tolosa, MD
Facility:
Name:
Hospital Universitario Central de Asturias
Address:
City:
Oviedo
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Yolanda Fernández
Facility:
Name:
Complejo Hospitalario de Navarra
Address:
City:
Pamplona
Country:
Spain
Status:
Recruiting
Investigator:
Last name:
Susana De la Cruz
Email:
Principal Investigator
Facility:
Name:
Hospital Universitari General de Catalunya
Address:
City:
Sant Cugat Del Vallès
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Vanesa Ortega
Facility:
Name:
Hospital Clínico de Valencia
Address:
City:
Valencia
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Cristina Hernando, MD
Start date:
October 3, 2023
Completion date:
January 2025
Lead sponsor:
Agency:
SOLTI Breast Cancer Research Group
Agency class:
Other
Source:
SOLTI Breast Cancer Research Group
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05982093
