Trial Title:
Elacestrant vs Elacestrant Plus a CDK4/6 Inhibitor in Patients With ERpositive/HER2-negative Advanced or Metastatic Breast Cancer
NCT ID:
NCT06062498
Condition:
Estrogen-receptor-positive Breast Cancer
HER2/Neu-Negative Breast Cancer
Advanced Breast Cancerv
Metastatic Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Palbociclib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
elacestrant, palbociclib, abemaciclib, ribociclib
Description:
Given orally
Arm group label:
Combination Therapy
Arm group label:
Elacestrant Monotherapy
Summary:
Breast cancer is not only the leading cause of cancer in women, but also the leading
cause of cancer deaths in women. Estrogen receptor-positive and HER2-negative breast
cancer is the most prevalent breast cancer subtype. Endocrine therapy is the mainstay of
treatment; however, due to the varied nature of the disease, development of resistance to
this therapeutic approach is very common in the metastatic setting.
The purpose of this study is to see whether the effectiveness of elacestrant can be
enhanced by combining it with a targeted agent such as a CDK4/6 inhibitor to treat
patients with ER+/HER2- or metastatic breast cancer with prior exposure to a CDK4/6
inhibitor.
Detailed description:
Primary Objective I. Evaluate progression-free survival (PFS) of patients with advanced
or metastatic ERpositive/HER2-negative breast cancer who have been treated with either
elacestrant monotherapy or combination therapy of elacestrant with a CDK4/6 inhibitor
(palbociclib, abemaciclib, or ribociclib). PFS of the elacestrant monotherapy arm will be
compared with PFS of the combination therapy arm.
Secondary Objectives I. Assess toxicity profile of elacestrant combination therapy with a
CDK4/6 inhibitor (palbociclib, abemaciclib, or ribociclib) in advanced or metastatic
ER-positive/HER2- negative breast cancer according to NCI-CTCAE v5.0.
II. Assess duration of response (DOR) in patients with advanced or metastatic
ERpositive/HER2-negative breast cancer who have been treated with either elacestrant
monotherapy or combination therapy of elacestrant with a CDK4/6 inhibitor (palbociclib,
abemaciclib, or ribociclib). DOR of the elacestrant monotherapy arm will be compared with
DOR of the combination therapy arm. III. Determine overall survival (OS) in patients with
advanced or metastatic ER-positive, HER2-negative breast cancer who have been treated
with either elacestrant monotherapy or combination therapy of elacestrant with a CDK4/6
inhibitor (palbociclib, abemaciclib, or ribociclib). OS of the elacestrant monotherapy
arm will be compared with OS of the combination therapy arm.
OUTLINE:
Patients will receive either elacestrant monotherapy or combination therapy with a CDK4/6
inhibitor (palbociclib, abemaciclib, or ribociclib) orally for each 28 day cycle until
progressive disease, unacceptable toxicity, treating physician decision, or patient
withdrawal of consent.
Patients will be followed (either by routine clinic visit or by phone call) every 36
weeks for 2 years and then every 72 weeks up to 5 years total from time of registration
to document survival and disease progression.
Criteria for eligibility:
Criteria:
Inclusion Criteria All Arms:
- Patients must have histologically or cytologically confirmed ER-positive and HER2-
negative breast cancer 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. Note: Fresh
biopsy is not a requirement.
- Patients must have a confirmed ESR1 mutation. Note: This information will be drawn
from patients' treatment charts. Mutational analysis will be done as standard of
care; there is no research-related mutational testing for this study. ctDNA may be
used for mutational testing.
- Patients must have at least one measurable lesion (as per RECIST v1.1) lesion
anywhere in the body or a mainly lytic metastatic bone lesion. Note: Lytic bone
lesions with identifiable soft tissue components that can be evaluated by
cross-sectional imaging techniques such as CT or MRI can be considered as measurable
lesions if the soft tissue component meets the definition of measurability per
RECIST v1.1.
- Patients must have received at least 2 prior endocrine therapies, including a CDK4/6
inhibitor in the metastatic disease setting.
- Patients must be age ≥ 18 years. Patients of childbearing potential (POCBP) may be
premenopausal, postmenopausal, or perimenopausal.
- Potential POCBP who may be menopausal and are < 55 years of age must have a serum
follicle-stimulating hormone (FSH) level > 40 mIU/mL to confirm menopause.
- Patients must exhibit an ECOG performance status of 0 or 1.
- Patients must have adequate organ and bone marrow function as defined below:
Leukocytes (WBC) ≥ 3,000/mcL Absolute neutrophil count (ANC) ≥ 1,500/mcL Hemoglobin (Hgb)
≥ 80-100 g/dL Platelets (PLT) ≥ 50,000/mcL Total serum bilirubin < 1.5 x Institutional
upper limit of normal (ULN) AST (SGOT) ≤ 3 x institutional ULN (no liver metastases)
- 5 x institutional ULN (liver metastases present) ALT (SGPT) ≤ 3 x institutional ULN
- 5 x institutional ULN (liver metastases present) Cockcroft-Gault based creatinine
clearance
- 50 mL/min
Note:
- Creatinine clearance (DMAB)
= ([140-age in years] × weight in kg)/ ([serum creatinine in mg/dL] × 72)
- Creatinine clearance (DFAB) = (0.85 × [140-age in years] × weight in kg)/ ([serum
creatinine in mg/dL] × 72) Note: Growth factor/transfusion support to attain these
levels is not permitted.
- For patients with a known history of human immunodeficiency virus (HIV),
infected patients on effective anti-retroviral therapy must have a viral load
undetectable for 6 months prior to registration.
- For patients with a known history of chronic hepatitis B virus (HBV) infection,
the HBV viral load must be undetectable on suppressive therapy, if indicated.
- Patients with a known history of hepatitis C virus (HCV) infection must have
been treated and cured. For patients with HCV infection who are currently on
treatment, they are eligible if they have an undetectable HCV viral load.
- Patients with a prior or concurrent malignancy whose natural history or
treatment does not have the potential to interfere with the safety or efficacy
assessment of the investigational regimen are eligible for this trial. Note:
Participants with basal cell carcinoma of the skin, squamous cell carcinoma of
the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in
situ) that have undergone potentially curative therapy are eligible.
- Patients with known history or current symptoms of cardiac disease, or history
of treatment with cardiotoxic agents, should have a clinical risk assessment of
cardiac function using the New York Heart Association Functional
Classification. To be eligible for this trial, patients should be class 2B or
better. Elacestrant is a known teratogen. For this reason, patients of
child-bearing potential (POCBP) and their partners with sperm-producing
reproductive capacity must agree to use adequate contraception (see Appendix B)
from time of informed consent, for the duration of study participation, and for
7 days following completion of elacestrant therapy.
Should a POCBP become pregnant or suspect they are pregnant while they or their partner
are participating in this study, they should inform their treating physician immediately.
Patients with sperm-producing reproductive capacity (PWSPRC) treated or enrolled on this
protocol must also agree to use adequate contraception with partners of childbearing
potential from time of informed consent, for the duration of study participation, and 7
days after completion of administration. Note: A POCBP is any patient (regardless of
gender, sexual orientation, having undergone a tubal ligation, or remaining celibate by
choice) with an egg-producing reproductive tract who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy
- Has had menses at any time in the preceding 12 consecutive months (and therefore has
not been naturally postmenopausal for > 12 months) Note: POCBP who are on
combination therapy with any study CKD4/6 inhibitor (palbociclib, abemaciclib, or
ribociclib) must agree to use adequate contraception from time of informed consent,
for the duration of study participation, and for 21 days following completion of
CKD4/6 inhibitor therapy. POCBP must have a negative pregnancy test prior to
registration on study. If initial urine pregnancy test is positive or cannot be
confirmed negative, serum pregnancy test will be required. -Patients must have the
ability to understand and the willingness to sign a written informed consent
document.
Inclusion Criteria - Combination Therapy Arm 2 with Palbociclib, Abemaciclib, or
Ribociclib
-Patients who have been treated with one or two prior hormonal therapies in the
metastatic setting if at least one hormonal therapy was in combination with a CDK4/6
inhibitor.
Notes:
- Patients who are already on or have already been exposed to one or two of the study
CDK4/6 inhibitors at registration will be assigned a different study CDK4/6
inhibitor (e.g., if a patient has already been exposed to abemaciclib, they will be
given ribociclib or palbociclib; similarly, if a patient has already been exposed to
palbociclib and abemaciclib, they will be given ribociclib.)
- One-to-one randomization will be done by the QA team once patients have been
registered.
Exclusion Criteria All Arms:
- Patients who have received prior elacestrant.
- Patients who have had chemotherapy or radiotherapy ≤ 28 days (6 weeks for
nitrosureas or mitomycin C) prior to registration.
- Patients who have taken steroid therapy or any other immunosuppressive therapy
within 7 days of first dose prior to trial treatment.
- Patients with brain metastases. Note: Patients with stable brain or subdural
metastases are allowed if the patient has completed local therapy and was on a
stable or decreasing dose of corticosteroids at baseline for brain management for at
least 4 weeks before starting treatment in this study. The dose must be <2.0 mg/day
of dexamethasone or equivalent. Any signs (e.g., radiologic) or symptoms of brain
metastases must be stable for at least 4 weeks before starting study treatment. RANO
criteria are used to evaluate brain metastases
- Patients who have not recovered from adverse events due to prior anti-cancer therapy
(i.e., have residual toxicities > Grade 3) with the exception of alopecia.
- Patients who are receiving any other investigational agents. For patients who were
previously on palbociclib, abemaciclib, or ribociclib, the washout period between
stopping that CDK4/6 inhibitor and starting a different one is 14 days.
- Patients with advanced, symptomatic visceral spread who are at risk of
life-threatening complications in the short term, including massive uncontrolled
effusions (peritoneal, pleural, pericardial), pulmonary lymphangitis, or liver
involvement >50%.
- Patients with documented pneumonitis/interstitial lung disease prior to
registration.
- Patients who have received major surgery within 28 days before starting trial
therapy.
- Patients who are taking strong or moderate CYP3A4 inducers or strong or moderate
CYP3A4 inhibitors. See Section 4.4 for additional incompatibilities.
- Patients who have a history of allergic reactions attributed to compounds of similar
chemical or biologic composition to elacestrant. Note: Refer to exclusion criteria
below for eligibility criteria related to study CDK4/6 inhibitors.
- Patients who have an uncontrolled intercurrent illness including, but not limited to
any of the following:
- Hypertension that is not controlled on medication
- Psychiatric illness/social situations that would limit compliance with study
requirements
- Any other illness or condition that the treating investigator feels would
interfere with study compliance or would compromise the patient's safety or
study endpoints
- Patients with refractory or chronic nausea, gastrointestinal conditions (including
significant gastric or bowel resection or gastric bypass surgery), history of
malabsorption syndrome, or any other uncontrolled gastrointestinal condition that
impact the absorption of the study drug. Similarly, patients who are unable to
take/retain oral medications.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Northwestern University
Address:
City:
Chicago
Zip:
60611
Country:
United States
Contact:
Last name:
William Gradishar, MD
Phone:
312-695-6180
Email:
cancer@northwestern.edu
Investigator:
Last name:
William Gradishar, MD
Email:
Principal Investigator
Start date:
September 30, 2023
Completion date:
July 1, 2025
Lead sponsor:
Agency:
Northwestern University
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Northwestern University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06062498
