A Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With The Physician's Choice of Endocrine Therapy Plus Everolimus in Participants With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer (evERA Breast Cancer)

B
Bryan Schneider, MD

Primary Investigator

Enrolling By Invitation
18 years - 100 years
All
Phase 3
320 participants needed
3 Locations

Brief description of study

What is the purpose of this study?
This Phase III, randomized, open-label, multicenter study will evaluate the efficacy andy of giredestrant plus everolimus compared with the physician's choice of endocrineherapy plus everolimus in participants with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who have had previous treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) anddocrine therapy, either in the locally advanced/metastatic or the adjuvant setting.

THIS STUDY IS ENROLLING BY INVITATION ONLY - Consistent with most oncology trials, patients are not actively “recruited,” but are screened by their physician for appropriate clinical trial(s) at the time of their routine clinic visit. Occasionally, a patient may be a self-referral or physician referral, but are still screened for appropriate clinical trials at the time of their routine clinic visit. PI and staff may send copies of relevant consent forms to these patients to look over prior to actually consenting or enrolling them. This may take place at the patient's visit at which the consent is presented or the patient's next visit to the outpatient hematology/oncology clinic.

Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office 
Phone: (317) 278-5632

Detailed description of study

What will happen during the study?
  • Eligible patients will be randomly assigned in a 1:1 ratio to either an experimental arm (giredestrant plus everolimus) or a control arm (exemestane plus everolimus). 
  • Patients will be stratified by prior treatment with fulvestrant (yes vs. no), ESR1 mutations (yes vs. no/indeterminant), and site of disease (visceral [any lung and/or liver involvement] vs. non- visceral [absence of any lung and/or liver involvement]).
  • Patients will receive open-label study drug as follows, beginning on Day 1 of Cycle 1:
  • Patients in the experimental arm will receive giredestrant 30 mg taken orally (PO) once a day (QD) and everolimus 10 mg taken orally QD on Days 128 of each 28-day cycle
  • Patients in the control arm will receive exemestane 25 mg taken orally QD and everolimus 10 mg taken PO QD on Days 128 of each 28-day cycle

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Estrogen Receptor (ER)-Positive, HER2-negative, Locally Advanced or Metastatic Breast Cancer
  • Age: 18 years - 100 years
  • Gender: All

Inclusion Criteria:
  1. Locally advanced unresectable or metastatic adenocarcinoma of the breast, not amenablewith curative intent
  2. Documented estrogen receptor-positive (ER+) tumor and HER2-negative tumor, assessedy
  3. Ability to provide a blood sample for circulating-tumor deoxyribonucleic acid (ctDNA)gen Receptor 1 (ESR1) mutation status determination by central testing
  4. Prior endocrine therapy (ET) in combination with cyclin-dependent kinase 4/6hibitors in either setting as follows:
    • Metastatic setting: Disease progression after ≥6 months on ET plus CDK4/6hibitor in the locally advanced or metastatic setting. If ET plus CDK4/6hibitor is not the most recent therapy, then patient must also have had diseasegression after ≥4 months on most recent ET
    • Adjuvant Setting: Relapse either while taking or within 12 months of exposure tobination adjuvant ET and CDK4/6 inhibitor. Patients must have taken at least12 months of adjuvant ET, 6 months of which was in combination with a CDK4/6hibitor.
  5. Measurable disease as defined per RECIST v.1.1 or evaluable bone metastases. Patients
    with evaluable bone disease in the absence of measurable disease outside of the boneust have at least one predominantly lytic bone lesion confirmed by computedgraphy (CT) or magnetic resonance imaging (MRI) which can be followed
  6. Eastern Cooperative Oncology Group Performance Status 0-1
  7. For women who are premenopausal or perimenopausal and for men: treatment with approveduteinizing hormone-releasing hormone (LHRH) agonist therapy for the duration of theudy treatment
Exclusion Criteria:
  1. Prior treatment with another oral selective estrogen receptor degrader (SERD),ysis targeting chimera (PROTAC), complete estrogen receptor antagonist (CERAN),vel oral selective estrogen receptor modulator (SERM), or everolimus in any setting.Prior fulvestrant is allowed if treatment was terminated at least 28 days prior todomization. Prior treatment with tamoxifen is allowed.
  2. Progression on more than 2 prior lines of systemic endocrine therapy in the locallydvanced unresectable or metastatic breast cancer setting
  3. Prior chemotherapy for locally advanced unresectable or metastatic disease
  4. Treatment with strong Cytochrome P450 3A4 (CYP3A4) inhibitors or inducers within 14days or 5 drug elimination half-lives (whichever is longer) prior to randomization
  5. Treatment with any investigational therapy within 28 days prior to initiation of study
  6. Major surgery, chemotherapy, radiotherapy, or other anti-cancer therapy within 14 daysdomization
  7. History of any other malignancy other than breast cancer within 5 years prior tog, except for appropriately treated carcinoma in situ of the cervix,kin carcinoma, papillary thyroid cancer treated with surgery, Stage Idometrial cancer, or other non-breast cancers at very low risk of recurrence
  8. Advanced, symptomatic, visceral spread that is at risk of life-threateninghe short term
  9. Known active uncontrolled or symptomatic central nervous system (CNS) metastases,us meningitis, or leptomeningeal disease
  10. Active cardiac disease or history of cardiac dysfunction
  11. Known clinically significant history of liver disease consistent with Child-Pugh ClassB or C including active viral or other hepatitis virus, current alcohol abuse, orhosis
  12. Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or majorupper gastrointestinal (GI) surgery including gastric resection
  13. Interstitial lung disease or severe dyspnea at rest or requiring oxygen therapy
  14. Serious infection requiring oral or intravenous (IV) antibiotics, or other clinicallygnificant infection, within 14 days prior to randomization
  15. Any serious medical condition or abnormality in clinical laboratory tests that, in thevestigator's judgment, precludes the patient's safe participation in and completionhe study
  16. Known allergy or hypersensitivity to any of the study drugs or any of their excipients
  17. For premenopausal or perimenopausal women and for men: known hypersensitivity to LHRHgonists
  18. Pregnant or breastfeeding

Updated on 01 Aug 2024. Study ID: ML43171, 17261
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