Elacestrant Monotherapy for the Treatment of ER+/HER2- Advanced Breast Cancer Following CDK4/6 Inhibitor Therapy: A Phase 3 Randomized, Open-Label, Active-Controlled, Multicenter Trial
- Conditions
- Advanced breast cancerTherapeutic area: Diseases [C] - Cancer [C04]MedDRA version: 20.0 Level: LLT Classification code 10072737 Term: Advanced breast cancer System Organ Class: 100000004864
- Registration Number
- EUCTR2018-002990-24-FR
- Lead Sponsor
- Radius Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 466
? Subjects with histologically or cytologically proven diagnosis of adenocarcinoma of the breast with evidence of either locally advanced disease not amenable to resection or radiation therapy with curative intent or metastatic disease not amenable to curative therapy
? Subjects must be appropriate candidates for endocrine monotherapy
? Subjects must have one of the terms as defined by RECIST v1.1 and confirmed by central radiology review prior to randomization:
a. Measurable disease
b. Nonmeasurable (evaluable) bone-only disease. Evaluable bone-only disease must include at least one lytic bone lesion or a mixed lytic-blastic bone lesion; blasticonly metastases are not allowed. Subjects who have had prior radiation to bone must have at least one evaluable lesion in a non-irradiated area
? Female or male subjects age = 18 years
? Female subjects must be postmenopausal, defined as:
a. Documented bilateral surgical oophorectomy
b. Age = 60 years with amenorrhea = 1 year since last menses
c. Age < 60 years with amenorrhea = 1 year since last menses with no alternative pathological or physiological cause (including chemotherapy, treatment with tamoxifen or toremifene, or a GnRH agonist), and serum estradiol and FSH level within the laboratory reference range for postmenopausal women
d. Age < 60 years with tamoxifen or toremifene therapy within the last 12 months, with documentation of 12 months of amenorrhea prior to tamoxifen or toremifene therapy, and serum estradiol and FSH levels within the laboratory reference range for postmenopausal women
? Male subjects:
a. Must have suppression of testicular hormone production through chemical ablation with an approved GnRH agonist, starting at least six weeks prior to study entry and continuing without interruption for the duration of protocol treatment (unless they have undergone prior orchiectomy). Note: GnRH agonists should be administered as per local standard of care and should be documented as concomitant medication
b. Must, even if surgically sterilized (ie, status post-vasectomy):
i. Agree to practice highly effective barrier contraception (use condoms) during the entire study treatment period and through 120 days after the last dose of study drug. For subjects (who have not undergone vasectomy) with female
partners of childbearing potential, the subject and his partner must in addition to condoms, use highly effective contraceptive measures when engaging in sexual intercourse throughout the study, and for at least 120 days after the last dose of study drug (eg, oral contraceptive and condoms, intrauterine device (IUD) and condoms, diaphragm with spermicide and condoms, other forms of contraception must be approved by the medical monitor) OR Agree to practice true abstinence during the entire study treatment period and through 120 days after the last dose of study drug
ii. Agree not to donate sperm during the course of this study or within 120 days after receiving their last dose of the study drugs
? Subjects must have ER-positive, HER2-negative tumor status confirmed per local laboratory testing on their most recent biopsy from a metastatic lesion (if metastatic disease), or recurrent disease lesion (if lo
? Prior treatment with elacestrant, GDC-0810, GDC-0927, GDC-9545, LSZ102, AZD9496, bazedoxifene, or other investigational selective estrogen receptor degrader (SERD) or investigational ER antagonist
? Prior anticancer or investigational drug treatment
? Presence of symptomatic metastatic visceral disease, defined as extensive hepatic involvement, untreated or progressive central nervous system (CNS) metastases, or symptomatic pulmonary lymphangitic spread. Subjects with discrete pulmonary parenchymal metastases are eligible, provided their respiratory function is not significantly compromised as a result of disease in the opinion of the Investigator. Subjects with previously treated CNS metastases are eligible provided that that all known lesions were previously treated, they have completed radiotherapy at least 28 days prior to first dose of study drug, are clinically stable, and require no steroid medication. If anti-convulsant medication is required, subjects must be stable on a non-enzyme inducing anticonvulsant regimen
? Subjects with an intact uterus with a history of endometrial intraepithelial neoplasia (atypical endometrial hyperplasia or higher-grade lesion)
? Diagnosis of any other malignancy within five years before enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix
? Any of the following within six months before enrollment: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias = Grade 2, prolonged QTcF = Grade 2, uncontrolled atrial fibrillation of any grade, coronary/peripheral artery bypass graft, heart failure > Class II as defined by the New York Heart Association (NYHA) guidelines (Appendix 5), or cerebrovascular accident including transient ischemic attack
? Subjects with abnormal coagulation profiles, or any history of coagulopathy within the past six months, including history of deep vein thrombosis (DVT) or pulmonary embolism. However, subjects with the following conditions will be allowed to participate: a.Subjects with adequately treated catheter-related venous thrombosis occurring more than one month prior to the first dose of study drug b.Subjects being treated with an anticoagulant, eg, warfarin or heparin, for a thrombotic event occurring more than six 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 stable for at least one month prior to the first dose of study drug, and provided that an AI would be an appropriate therapy for the subject
? Subjects with known difficulty in tolerating oral medications or conditions which would impair absorption of oral medications such as: uncontrolled nausea or vomiting, gastrointestinal obstruction/motility disorder, malabsorption syndrome, or prior gastric bypass
? Subjects unable or unwilling to avoid prescription medications, over the counter medications, dietary/herbal supplements, and/or foods (eg, pomelos, star fruit, Seville oranges, and their juices) that are strong inhibitors or inducers of CYP3A4 activity, or cholestyramine or other anion exchange resins. Participation will be allowed if the medication, supplements and/or foods are discontinued for at least five half-lives or
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method