Postmenopausal female subjects with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer, who have progressed on an aromatase inhibitor (AI) MedDRA version: 18.1 Level: LLT Classification code 10006315 Term: Breast tumor malignant System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 18.1 Level: LLT Classification code 10006204 Term: Breast carcinoma System Organ Class:
Conditions
Interventions
Product Name: Oral Azacitidine
Product Code: CC-486
Pharmaceutical Form: Coated tablet
INN or Proposed INN: AZACITIDINE
CAS Number: 320-67-2
Current Sponsor code: CC-486
Concentration unit: mg milligr
Sponsors
Celgene Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Subject is female =18 years of age (at the time of signing the informed consent form) with metastatic breast cancer not amenable to curative treatment by surgery or radiotherapy. -Subject is considered postmenopausal -Subject has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive breast cancer by local laboratory (based on most recently analyzed biopsy). -Subject has human epidermal growth factor receptor 2 negative (HER2-) breast cancer (based on most recently analyzed biopsy) defined as a negative in situ hybridization test or an Immunohistochemistry (IHC) status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing. -Subject had disease refractory to an AI -Subject has an Eastern Cooperative Oncology Group ( ECOG) performance status of 0-1. - Subject has radiological documented measurable disease (ie, at least one measureable lesion as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1). •If no measurable disease is present, then at least one predominantly lytic bone lesion must be present -Subject has adequate organ function. -Subject has adequate bone marrow function. 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 55 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 37
Exclusion criteria
Exclusion criteria: -Subject has received > 1 prior line of chemotherapy in the metastatic setting -Subject has received any chemotherapy within 21 days prior to randomization. -Subject has received prior treatment with fulvestrant. -Subject has been previously treated with azacitidine (any formulation), decitabine, or any other hypomethylating agent. -Subject has a history of, or current symptomatic brain metastasis. -Subject has severe renal impairment (creatinine clearance < 30 ml/min). - Subject has an impaired ability to swallow oral medication. -Subject has a contraindication to receiving IM injections (eg, bleeding disorders, anticoagulant use). -Subject has significant active cardiac disease within the previous 6 months including unstable angina or angina requiring surgical or medical intervention, significant cardiac arrhythmia, or New York Heart Association (NYHA) class 3 or 4 congestive heart failure. -Subject is a female of Childbearing Potential [defined as a sexually mature woman who (1) has not undergone hysterectomy (the surgical removal of the uterus) or bilateral oopherectomy (the surgical removal of both ovaries) or (2) has not been naturally postmenopausal for at least 12 consecutive months (ie, has had menses at any time during the preceding 12 consecutive months)].
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of CC-486 in combination with fulvestrant relative to fulvestrant monotherapy, by estimation of the hazard ratio of progression free survival (PFS);Secondary Objective: •To estimate response rate (RR), clinical benefit rate (CBR), overall survival (OS), and duration of response (DOR) in all treatment arms •To evaluate the safety of all treatment arms;Primary end point(s): Estimation of the hazard ratio of PFS of the combination arm relative to fulvestrant monotherapy arm;Timepoint(s) of evaluation of this end point: approximately 28 months after the start of enrollment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •ORR: the combined incidence of CR and PR, based on RECIST Version 1.1 •Clinical benefit rate (CBR) : [Complete response (CR) + PR + SD ( = 24 weeks)] •Overall Survival (OS): time from date of randomization to date of death due to any cause •Duration of response in subjects with objective CR or PR •Safety: incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), Grade 3 and higher AEs, AEs of special interest, and laboratory abnormalities and other safety parameters;Timepoint(s) of evaluation of this end point: •ORR: approximately 28 months after the start of enrollment •CBR: approximately 28 months after the start of enrollment •OS: approximately 28 months after the start of enrollment •Duration of response: approximately 28 months after the start of enrollment •Safety: Continuous starting after signature of informed consent document, until 28 days after treatment discontinuation | — |
Countries
Belgium, France, Germany, Italy, Spain, United States
Contacts
Public ContactClinicalTrialDisclosure
Celgene Corporation
Outcome results
None listed