A Phase 2 Randomized Pre-operative,Window of Opportunity Trial Investigating the Effect of Elacestrant With/Without Triptorelin in Premenopausal Patients With HR+/HER2- Breast Cancer - SOLTI-2104-PremiÈRe Trial.
Overview
- Phase
- Phase 2
- Intervention
- Elacestrant
- Conditions
- Breast Cancer
- Sponsor
- SOLTI Breast Cancer Research Group
- Enrollment
- 96
- Locations
- 24
- Primary Endpoint
- To evaluate the biological activity of elacestrant with or without OFS in premenopausal women with ER+/HER2- operable EBC
- Status
- Recruiting
- Last Updated
- 8 days ago
Overview
Brief 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 Part A and Part B are parallel, non-comparative, two-arm, randomized 1:1, open-label, multicenter, exploratory trials designed to evaluate the biological activity of elacestrant in premenopausal women with primary operable HR+/HER2- BC. Eligible patients must have histologically confirmed, operable, HR+/HER2-invasive breast cancer \>1 cm, with a Ki67 between 10-35%, be treatment-naïve, and meet all other inclusion and exclusion criteria. An FFPE tumor sample of sufficient quality must be available, if not, patients must agree to undergo a re-biopsy. In Part A, patients are randomized 1:1 to receive one of the following regimens: * Elacestrant arm: 400 mg orally once daily for 30 (+7) days. * Elacestrant + triptorelin arm: same elacestrant schedule plus triptorelin 3.75 mg on days 1 and 29. In Part B, patients are randomized 1:1 to receive one of the following regimens: * Elacestrant arm: 400 mg orally once daily for 30 (+7) days * Tamoxifen arm: 20 mg orally once daily for 30 (+7) days. Randomization is stratified by PAM50 intrinsic subtype (Luminal A vs non-Luminal A), determined by research-based molecular profiling. During the treatment period, blood samples will be collected for the isolation of plasma and serum at baseline, Day 14, Day 28, and post-treatment. In PremiÈRe Part B only, optional transvaginal ultrasound (TVUS) assessments may be performed at baseline, Day 28, and at the End of Study visit, to explore changes in ovarian and uterine parameters. Following treatment, breast and axillary surgery will be performed according to local practice procedures. Pre-surgical sentinel lymph node biopsy (SLNB) is not allowed. Surgical specimens (or mandatory biopsy samples if no surgery is planned) will be collected for analysis. A post-surgery visit will occur within 28 ± 14 days and will mark the end of active follow-up.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed informed consent must be obtained prior to any trial-specific procedure.
- •Female patients who are at least 35 years of age on the day of signing informed consent.
- •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.
- •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.
Exclusion Criteria
- •Inoperable locally advanced or inflammatory breast cancer (any stage III).
- •Metastatic (Stage IV) breast cancer.
- •Synchronous invasive bilateral or multicentric breast cancer.
- •Patients requiring immediate neoadjuvant chemotherapy or immediate surgical intervention.
- •Patients who have undergone sentinel lymph node biopsy or tumor excisional biopsy prior to study treatment.
- •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.
- •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
Arms & Interventions
Elacestrant
without ovarian function suppression
Intervention: Elacestrant
Elacestrant + Triptorelin
with ovarian function suppression
Intervention: Elacestrant
Elacestrant + Triptorelin
with ovarian function suppression
Intervention: Triptorelin
Tamoxifen
monotherapy
Intervention: Tamoxifen 20 mg
Outcomes
Primary Outcomes
To evaluate the biological activity of elacestrant with or without OFS in premenopausal women with ER+/HER2- operable EBC
Time Frame: After 30 days (+7 days) of elacestrant therapy
Rate of CCCA determined by central assessment by IHC Ki67 (% Ki67 ≤ 2.7%) after 4 weeks of therapy.
To evaluate the biological activity of elacestrant with or without OFS in premenopausal women with ER+/HER2- operable EBC
Time Frame: After 30 days (+7 days) of therapy
Rate of CCCA determined by central assessment by IHC Ki67 (% Ki67 ≤ 2.7%) after 4 weeks of therapy.
Secondary Outcomes
- To evaluate levels of FSH in blood.(After 14 days (+2 days) of elacestrant therapy)
- To evaluate the effect of optimal and suboptimal OFS (E2 level greater than 2.72 pg/mL) in CCCA(After 30 days (+7 days) of elacestrant therapy)
- To evaluate the biological activity of elacestrant with or without OFS in premenopausal women with ER+/HER2- operable EBC according to baseline research-based PAM50 subtype.(After 30 days (+7 days) of elacestrant therapy)
- To evaluate the safety of the treatments when administered in pre-menopausal patient population.(Until End of Study Visit (7-28 days after surgery)])
- To evaluate the antiproliferative activity of elacestrant with or without OFS after -treatment(After 30 days (+7 days) of elacestrant therapy)
- To identify changes in the research-based PAM50 subtypes pre- and post-treatment samples after treatment(After 30 days (+7 days) of elacestrant therapy)
- To evaluate levels of E2 in blood.(After 14 days (+2 days) of elacestrant therapy)
- To evaluate the tolerability of the treatments when administered in pre-menopausal patient population.(Until End of Study Visit (7-28 days after surgery)])
- To evaluate the biological activity of elacestrant with or without OFS in premenopausal women with ER+/HER2- operable EBC according to baseline research-based PAM50 subtype.(After 30 days (+7 days) of therapy)
- To evaluate the antiproliferative activity of elacestrant with or without OFS after -treatment(After 30 days (+7 days) of therapy)
- To identify changes in the research-based PAM50 subtypes pre- and post-treatment samples after treatment(After 30 days (+7 days) of therapy)
- To evaluate the effect of optimal and suboptimal OFS (E2 level greater than 2.72 pg/mL) in CCCA(After 30 days (+7 days) of therapy)
- To evaluate levels of E2 in blood.(After 14 days (+2 days) of therapy)