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 cancerMedDRA version: 21.1Level: LLTClassification code 10072737Term: Advanced breast cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-002990-24-AT
- Lead Sponsor
- Radius Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 466
? Must have 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
? Must be appropriate candidates for endocrine monotherapy
? Must have 1 of the following as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1:
a. Measurable disease
b. Bone-only disease with evaluable lesions. Subjects must have at least 1 lytic or mixed lytic-/blastic bone lesion; blastic- lesions only are not
evaluable and allowed. Subjects who have had prior radiation to bone must have at least 1 evaluable lesion in a nonirradiated area
? Female or male = 18 years of age
? Female subjects must be post-menopausal, defined by 1 of the following criteria:
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 ongoing or recent chemotherapy, treatment with tamoxifen or toremifene, or a GnRH agonist), and serum estradiol and follicle stimulating hormone (FSH) levels within the laboratory reference range for post-menopausal 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 post-menopausal women
e. Females with hormonally-induced menopause (ie, requiring ongoing hormone suppression) are not eligible
? Male subjects must, even if surgically sterilized (ie, status postvasectomy):
a. 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 treatment period and for at least 120 days after the last dose of study drug (ie, oral contraceptive and condoms, intrauterine device 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
Note: Abstinence should only be used as a contraceptive method if it is in line with the subject's usual and preferred lifestyle. Periodic abstinence (calendar symptothermal, post-ovulation methods) is not an acceptable method of contraception.
b. Agree not to donate sperm during the course of treatment period of this study or within 120 days after receiving the last dose of the study drug
? Must have ER+ and HER2- tumor status confirmed per local laboratory testing. Status may be confirmed on original diagnosis tissue samples or post-treatment samples (most recent biopsy preferred, if testing available)
? Must have previously received at least 1 and no more than 2 lines of endocrine therapy, either as monotherapy or as a combination therapy with another agent (eg, phosphoinositide 3-kinase [PI3K] inhibitor), for mBC
? Must have progressed during or within 28 days of completion of prior treatment with a CDK4/6 in
? Prior treatment with elacestrant or investigational SERD or ER antagonist (eg, D-0502, GDC-0810, GDC-0927, GDC-9545, G1T-48, LSZ102, AZD9496, SAR439859, ZN-c5, H3B-6545, bazedoxifene, lasofoxifene)
? Prior anti-cancer or investigational drug treatment
? Radiation therapy within 14 days (28 days for brain lesions per Exclusion Criterion 4) before the first dose of study drug
? Presence of symptomatic metastatic visceral disease, including but not limited to, 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, and are clinically stable. If anticonvulsant medication is required, subjects must be stable on a non-enzyme inducing anticonvulsant regimen
? Intact uterus with a history of endometrial intraepithelial neoplasia (atypical endometrial hyperplasia or higher-grade lesion)
? Diagnosis of any other malignancy within 5 years before enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix or second primary breast cancer
? 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 (ie, > 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
? Child-Pugh-Score greater than Class A (ie, score >6)
? 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:
a. Adequately treated catheter-related venous thrombosis occurring >28 days prior to the first dose of study drug
b. Treatment with an anticoagulant, eg, 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 stable for at least 28 days prior to the first dose of study drug, and provided that an AI would be an appropriate therapy for the subject
? Known bleeding disorder which, in the opinion of the Investigator, would prohibit administration of fulvestrant if that would be SOC choice for the subject
? Known difficulty in tolerating oral medications or conditions which would impair absorption of oral medications such as: uncontrolled nausea or vomiting (ie, CTCAE = Grade 3 despite antiemetic therapy), ongoing gastrointestinal obstruction/motility disorder, malabsorption syndrome, or prior gastric bypass
? Unable or unwilling to avoid prescription medications, over the counter medications, dietary/herbal supplements (eg, St. John's wort), and/or foods (eg, grapefruit, pomelos, star fruit, Seville oranges, and their juices) that are moderate/strong inhibitors or inducer
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