Advanced Estrogen Receptor Positive HER2-Breast Cancer MedDRA version: 19.1 Level: LLT Classification code 10070575 Term: Estrogen receptor positive breast cancer System Organ Class: 100000004864
Conditions
Interventions
Product Code: GS-5829
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: GS-5829
Current Sponsor code: GS-5829
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration num
Sponsors
Gilead Sciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) = 18 years of age, female 2) Histologically or cytologically confirmed breast cancer with evidence of metastatic or locally advanced disease not amenable to resection or radiation therapy with curative intent and who have progressed during treatment with at least one prior hormonal therapy 3) Documentation of ER positive based on the most recent tumor biopsy, unless bone-only disease. 4) Documented HER2-negative tumor based on local testing on most recent tumor biopsy 5) Post -menopausal subjects considered to be in the post-menopausal state as defined in the protocol 6) Measurable disease defined per RECIST v. 1.1 or bone-only disease must have a lytic or mixed lytic blastic lesion that can be accurately assessed by CT or MRI. Subjects with bone-only disease and blastic-only metastases are not eligible 7) All acute toxic effects of any prior antitumor therapy resolved to Grade = 1 before the start of study drug dosing 8) Eastern Cooperative Oncology Group (ECOG) Performance Status of = 1 9) Life expectancy of = 3 months, in the opinion of the investigator 10) Adequate organ function 11) Coagulation: International Normalized Ratio (INR) = 1.2 12) Negative serum pregnancy test 13) Female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception 14) Females who are nursing must agree to discontinue nursing before the first dose of GS-5829 15) Able and willing to provide written informed consent to participate in the study Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 120 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1) History or evidence of clinically significant disorder, condition, or disease that, in the opinion of the investigator or the Gilead medical monitor would pose a risk to subject safety or interfere with the study evaluations, procedures, or completion 2) Known brain metastasis or leptomeningeal disease 3) Uncontrolled intercurrent illness including, but not limited to, active uncontrolled infection, active or chronic bleeding event within 28 days prior to first dose of study drug, uncontrolled cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements as judged by treating physician 4) Myocardial infarction, symptomatic congestive heart failure , unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months of C1D1 5) Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision within 28 days of the first dose of study drug 6) Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of GS-5829, including any unresolved nausea, vomiting, or diarrhea that is CTCAE Grade > 1 7) Minor surgical procedure(s) within 7 days of enrollment or randomization, or not yet recovered from prior surgery 8) History of a concurrent or second malignancy, except for: adequately treated local basal cell or squamous cell carcinoma of the skin; cervical carcinoma in situ; superficial bladder cancer; adequately treated Stage 1 or 2 cancer currently in complete remission; any other cancer that has been in complete remission for = 5 years 9) Anti-tumor therapy within 21 days of study drug dosing ; 5 half-lives of any investigational drug; concurrent use of goserelin for pre-/peri-menopausal breast cancer and exemestane or fulvestrant per the protocol are permitted 10) History of long QT syndrome or whose corrected QT interval (QTc) measured (Fridericia method) at screening is prolonged (> 470 ms). Subjects who screen fail due to this criterion are not eligible to be re-screened 11) Prior exposure to any bromodomain (BET) inhibitors 12) Immunotherapy within 6 months of C1D1 13) Evidence of bleeding diathesis or clinically significant bleeding, within 28 days of C1D1 or history of hemoptysis of > 2.5mL/1 teaspoon within 6 months of C1D1 14) Anticoagulation therapy within 7 days of C1D1, including acetylsalicylic acid, low molecular weight heparin, or warfarin 15) Known human immunodeficiency virus (HIV) infection 16) Hepatitis B surface Antigen (HBsAg) positive 17) Hepatitis C virus (HCV) antibody positive with HCV RNA positive 18) Use of moderate/strong cytochrome P450 (CYP) 3A4 inhibitors or moderate/strong CYP3A4 inducers within 2 weeks prior to the first dose of study drug 19) History of high grade esophageal or gastric varices
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Dose Escalation: Characterize the safety and tolerability of GS-5829 in combination with exemestane or fulvestrant in subjects with advanced estrogen receptor positive Her2-negative breast cancer (ER+/HER2- BrCa); determine the MTD or the recommended Phase 2 dose (RP2D) of GS-5829 in combination with exemestane or fulvestrant in subjects with advanced ER+/HER2- BrCa. Dose Expansion: Evaluate the efficacy of GS-5829 in combination with exemestane compared to exemestane alone in subjects with advanced ER+/HER2- BrCa; evaluate the efficacy of GS-5829 in combination with fulvestrant compared to fulvestrant alone in subjects with advanced ER+/HER2- BrCa.;Secondary Objective: Dose Escalation: Evaluate the pharmacokinetics PK of GS-5829 in combination with exemestane or fulvestrant in subjects with advanced ER+/HER2- BrCa. Dose Expansion: Evaluate the efficacy of GS-5829 in combination with exemestane compared to exemestane alone in subjects with advanced ER+/HER2- BrCa. Evaluate the efficacy of GS-5829 in combination with fulvestrant compared to fulvestrant alone in subjects with advanced ER+/HER2- BrCa. Evaluate the safety and tolerability of GS-5829 in combination with exemestane compared to exemestane alone in subjects with advanced ER+/HER2- BrCa. Evaluate the safety and tolerability of GS-5829 in combination with fulvestrant compared to fulvestrant alone in subjects with advanced ER+/HER2- BrCa. To evaluate the overall survival (OS) for subjects with advanced ER+/HER2-BrCa who receive GS-5829 in combination with exemestane or fulvestrant comparing to exemestane or fulvestrant alone.;Primary end point(s): Dose Escalation: Safety profile and tolerability of the combination of GS-5829 and exemestane or fulvestrant as assessed by the incidence of dose limiting toxicities. Dose Expansion: PFS.;Timepoint(s) of evaluation of this end point: Study visits occur on Days 1 and 15 of cycles 1 and 2., and every 4 weeks thereafter. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Dose Escalation: GS-5829 PK parameters Dose Expansion: Overall safety profile Overall response rate Clinical benefit rate Overall survival;Timepoint(s) of evaluation of this end point: Study visits occur on Days 1 and 15 of cycles 1 and 2., and every 4 weeks thereafter. | — |
Countries
Belgium, France, Italy, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trials Mailbox
Gilead Sciences International Ltd.
Outcome results
None listed