Estrogen receptor (ER)-positive, HER2 negative locally advanced or metastatic breast cancer who have received one or two prior lines of systemic therapy in the locally advanced (recurrent or progressed) or metastatic setting MedDRA version: 23.0 Level: LLT Classification code 10070575 Term: Estrogen receptor positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 23.0 Level: LLT Classification code 10070577 Term:
Conditions
Interventions
Product Name: GDC-9545
Product Code: Ro 719-7597/F12-01
Pharmaceutical Form: Capsule
INN or Proposed INN: NAP
Current Sponsor code: RO7197597
Other descriptive name: GDC-9545
Concentration unit: mg mi
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Age >= 18 years of age •For women: postmenopausal or premenopausal/perimenopausal status oAge >= 60 years oAge = 12 months of amenorrhea plus follicle-stimulating hormone and plasma estradiol levels within postmenopausal range by local laboratory assessment, in the absence of oral contraceptive pills, hormone replacement therapy, or gonadotropin releasing hormone agonist or antagonist oDocumented bilateral oophorectomy oPremenopausal/perimenopausal or men, be willing to undergo and maintain treatment with approved LHRH-agonist therapy •Histologically or cytologically confirmed diagnosis of locally advanced (recurrent or progressed) or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent •Disease progression after treatment with one or two lines of systemic therapy in the locally advanced or metastatic setting •Documented ER-positive tumor according to American Society of Clinical Oncology/College of American Pathologists guidelines •Documented HER2-negative tumor assessed locally •Availability of the most recently collected and representative tumor tissue specimen, with associated de identified pathology report, and whenever possible, from a metastatic site of disease •Measurable disease as defined per Response Evaluation Criteria in Solid Tumors, Version 1 •Eastern Cooperative Oncology Group Performance Status 0-1 •Life expectancy of > 6 months •Adequate organ function •INR =65 years) yes F.1.3.1 Number of subjects for this age range 75
Exclusion criteria
Exclusion criteria: •Prior treatment with a SERD, with the exception of fulvestrant, if fulvestrant treatment was terminated at least 28 days prior to randomization •Treatment with any investigational therapy within 28 days prior to randomization •Major surgery, chemotherapy, radiotherapy, or other anti-cancer therapy within 14 days prior to randomization •History of malignancy other than breast cancer within 5 years prior to screening •Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term •Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease •Active cardiac disease or history of cardiac dysfunction •Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis virus, current alcohol abuse, or cirrhosis •Known HIV infection •Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major upper gastrointestinal surgery, including gastric resection, potentially affecting enteral absorption •Serious infection requiring oral or IV antibiotics within 14 days prior to randomization •Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study •Known allergy or hypersensitivity to any of the study drugs or any of their excipients •For premenopausal/perimenopausal patients or male patients: known hypersensitivity to LHRH agonists •Pregnant or breastfeeding, or intending to become pregnant during the study or within 8 days after the final dose of GDC-9545, or within the time period specified per local prescribing guidelines after the final dose of physician's choice of endocrine monotherapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -To evaluate the efficacy of GDC-9545 compared with physician's choice of endocrine monotherapy on the basis of progression free survival;Primary end point(s): 1. Progression free Survival as determined by the investigator;Secondary Objective: -To evaluate the efficacy of GDC-9545 compared with physician's choice of endocrine monotherapy on the basis of overall survival, objective response rate, duration of response, clinical benefit rate, investigator-assessed progression free survival, time to deterioration in pain severity, pain presence and interference, physical functioning, role functioning and global health status and quality of life after randomization -To evaluate the safety of GDC-9545 compared with physician's choice of endocrine monotherapy -To characterize the GDC-9545 pharmacokinetics profile ;Timepoint(s) of evaluation of this end point: 1. Approximately 40 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall survival 2. Objective response rate as determined by the investigator 3. Duration of response as determined by the investigator 4. Clinical benefit rate as determined by the investigator 5. Investigator-assessed progression free survival n subgroups categorized by baseline ESR1 mutation status 6. Time to deterioration in pain severity 7. Time to deterioration in pain presence and interference 8. Time to deterioration in physical functioning 9. Time to deterioration in role functioning 10. Time to deterioration in global health status and quality of life 11. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 12. Change from baseline in targeted vital signs 13. Change from baseline in targeted clinical laboratory test results 14. Plasma concentration of GDC-9545 at specified timepoints ;Timepoint(s) of evaluation of this end point: 1-11. Approximately 40 months 12-13. From Baseline (Day -28 to Day -1) to 40 months 14. Day 1 of Cycle 1-3 and Day 1 of every two cycles thereafter through Cycle 15 and at treatment discontinuation visit | — |
Countries
Argentina, Australia, Brazil, China, Germany, Israel, Korea, Republic of, Poland, Russian Federation, Serbia, South Africa, Thailand, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed