Metastatic breast cancer
Conditions
Interventions
RAD1901 will be supplied as 100-mg capsules to be administered orally.
Sponsors
Radius Pharmaceuticals, Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Patients with histologically-proven, ER-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced, inoperative, and/or mBC.;a) ER-positive tumour defined as * 1% staining by IHC as defined in the 2010 ASCO recommendations for ER testing.;b) HER2-negative tumour defined as an IHC result of 0 or 1+ for cellular membrane protein expression, or fluorescence in situ hybridisation (ISH) negative result as defined in the 2013 ASCO recommendations for HER2 testing.;2. Tumour progression after * 6 months of at least 1 line of hormonal systemic treatment (SERM, SERD, or aromatase inhibitor) in the metastatic setting;3. Measurable disease according to RECIST criteria v1.1 or clinically evaluable disease. At least 1 non-irradiated lesion (measurable and/or non-measurable) that can be accurately assessed by CT/magnetic resonance imaging/plain X-ray at baseline and follow-up visits;4. Greater than or equal to 18 years of age;5. Patients must be post-menopausal defined as follows:;a) Greater than 56 years of age with amenorrhea for > 12 months;b) Less than 56 years of age with amenorrhea for > 12 months, serum estradiol levels < 20 pg/mL, and follicle stimulating hormone levels > 40 mIU/mL;c) Prior bilateral ovariectomy;d) Pre-menopausal patients who are medically induced to become post-menopausal for purposes of receiving endocrine therapy as standard of care treatment are eligible with documentation of appropriate lab testing;6. No prior treatment with RAD1901, GDC-0810, AZD9496, or other investigational SERD.;7. Eastern Cooperative Oncology Group performance status 0-2;8. Life expectancy > 3 months;9. Resolution of all toxic effects of prior therapy or surgical procedures to Grade * 1 (except alopecia);10. Adequate organ function as defined below:;a) Adequate bone marrow function;* absolute neutrophil count * 1.5 x 109/L;* platelets * 75 x 109/L;b) Adequate hepatic function;* Total bilirubin * 1.5 x upper limit of normal (ULN) regardless of liver metastases. Inclusion of patients with increased serum indirect bilirubin (* 3 x ULN) due to Gilbert*s syndrome is permitted;* Aspartate aminotransferase (AST), alanine aminotransferase (ALT) * 3 x ULN, or AST and ALT * 5 x ULN, if liver metastases are present;* International Normalised Ratio (INR) < 1.6 x ULN;c) Adequate renal function;* Creatinine * 1.5 x ULN for institutional limits OR creatinine clearance > 60 mL/min/1.73 m2 calculated by the Cockcroft-Gault formula for patients with creatinine levels above institutional normal;11. Written informed consent must be given according to International Conference on Harmonisation, Good Clinical Practice, and national regulations;12. Able to comply with protocol
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating women;2. Severe concurrent disease, infection, or co-morbid condition that, in the judgment of the investigator would make the patient inappropriate for enrollment;3. Greater than 3 lines of endocrine therapy for metastatic disease;4. Prior anti-cancer treatment or investigational drug therapy within the following windows:;a) Tamoxifen or fulvestrant therapy < 42 days before 1st 18FES-PET scan;b) Any other anti-cancer endocrine therapy < 14 days before 1st dose of study drug;c) Any chemotherapy < 28 days before 1st dose of study drug;d) Any investigational drug therapy < 28 days or 3 half-lives (whichever is longer) prior to the 1st dose of study drug;5. Patient with metastatic disease involving only the liver.;6. Patients with untreated or symptomatic central nervous system metastases. Note: For patients with CNS metastases to be eligible, they must have completed radiotherapy at least 14 days prior to enrollment and require no steroid medication. If anticonvulsant medication is required, patients must be stable on a non-enzyme-inducing anticonvulsant regimen.;7. Patients with known endometrial disorders, including evidence of endometrial hyperplasia, dysfunctional uterine bleeding, or cysts;8. Diagnosis of any secondary malignancy within 6 months prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ;9. Any of the following within 6 months prior to enrollment: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias Grade > 2, uncontrolled atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic cardiac failure, or cerebrovascular accident, including transient ischemic attack;10. Patients with a history of any of the following blood disorders:;a) Patients being treated with anticoagulant, e.g, warfarin or heparin, will be allowed to participate provided dose and coagulation parameters (as defined by local standard of care) are stable for at least 1 month prior to the 1st dose of study drug.;b) Any history of coagulopathy, including history of deep vein thrombosis or pulmonary embolus within the past 6 months (except for adequately treated catheter-related venous thrombosis occurring > 1 month prior to the 1st dose of study drug);11. Known human immunodeficiency virus infection, or active hepatitis C or hepatitis B virus infection;12. Patient has impairment of gastrointestinal function or disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, uncontrolled vomiting, chronic or uncontrolled diarrhoea, malabsorption syndrome, gastric bypass, or small bowel resection);13. Major surgery within 28 days prior to the 1st dose of study drug;14. Local radiation therapy within 7 days prior to 1st dose of study drug;15. Use of strong cytochrome P450 (CYP)3A4/5 inhibitors and strong CYP3A4/5 inducers that cannot be discontinued 7 days prior to the start and for the duration of study treatment;16. Patients with an endometrial thickness > 11 mm
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of this study is: * To determine the effect of RAD1901 treatment on the estrogen receptor (ER) expression and estradiol binding to the ER in lesions from patients with metastatic breast cancer (mBC) as measured by 16* 18F fluoro-17*-estradiol (18FES) positron emission tomography (PET) imaging | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary objectives of this study are: * To correlate changes in 18FES uptake after RAD1901 treatment to clinical responses measured by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 * To evaluate the preliminary anti-tumour effects of RAD1901 * To assess the safety and tolerability of RAD1901 * To assess the pharmacokinetics of RAD1901 The exploratory objectives of this study are: * To explore the relationship between ER mutation status in circulating tumour deoxyribonucleic acid (ctDNA) in plasma and clinical response * To explore the effect of RAD1901 on ER/progesterone receptor and Ki67 tumour markers in tumour biopsies and correlate the effects to clinical response * To explore the effect of RAD1901 on circulating tumour cells (CTCs) | — |
Countries
Netherlands
Outcome results
None listed