Description:
The purpose of this study to Assess the Efficacy and Safety of the Epigenetic Modifying
Effects of CC-486 (Oral Azacitidine) in Combination With Fulvestrant in Postmenopausal Women
with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 (HER2-)
Metastatic Breast Cancer Who Have Progressed on an Aromatase Inhibitor (AI).
Title
- Brief Title: Study to Assess the Efficacy and Safety of the Epigenetic Modifying Effects of CC-486 (Oral Azacitidine) in Combination With Fulvestrant
- Official Title: A Phase 2, Randomized, Open-label, Two-arm Study to Assess the Efficacy and Safety of the Epigenetic Modifying Effects of CC-486 (Oral Azacitidine) in Combination With Fulvestrant in Postmenopausal Women With ER+, HER2- Metastatic Breast Cancer Who Have Progressed on an Aromatase Inhibitor
Clinical Trial IDs
- ORG STUDY ID:
CC-486-BRSTM-001
- NCT ID:
NCT02374099
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| CC-486 | Oral Azacitidine | CC-486 and fulvestrant |
| Fulvestrant | Faslodex | CC-486 and fulvestrant |
Purpose
The purpose of this study to Assess the Efficacy and Safety of the Epigenetic Modifying
Effects of CC-486 (Oral Azacitidine) in Combination With Fulvestrant in Postmenopausal Women
with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 (HER2-)
Metastatic Breast Cancer Who Have Progressed on an Aromatase Inhibitor (AI).
Detailed Description
This is a Phase 2, open-label, two-arm study assessing the efficacy and safety of the
combination of fulvestrant with CC-486 in subjects with ER+, HER2- metastatic breast cancer
who have progressed after prior AI.
Approximately 92 participants will be enrolled and assigned randomly in a 1:1 ratio to one of
two treatment arms:
- Arm A: CC-486 300 mg and fulvestrant 500 mg: 46 subjects
- Arm B: Fulvestrant 500 mg: 46 subjects Each cycle will be 28 days. CC-486 will be
administered orally at a dose of 300 mg daily on days 1-21 of each 28-day cycle.
Fulvestrant will be administered by intramuscular (IM) injection at a dose of 500 mg on
days 1 and 15 of cycle 1 and day 1 of subsequent cycles.
Safety will be evaluated by an independent data monitoring committee (DMC) after a total of
approximately 32 subjects have completed at least 1 treatment cycle.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| CC-486 and fulvestrant | Experimental | CC-486 300 mg by mouth (PO) daily on days 1-21 of each 28 day cycle and fulvestrant 500mg by intramuscular (IM) injection on Days 1 and 15 of cycle 1 and day 1 of each subsequent cycle every 28 days. | |
| Fulvestrant | Experimental | Fulvestrant will be administered by intramuscular injection at a dose of 500 mg on days 1 and 15 of cycle 1 and day 1 of subsequent cycles. | |
Eligibility 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.
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)].
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Female |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Kaplan-Meier Estimate of Progression Free Survival (PFS) |
| Time Frame: | From the date of randomization of study drug to the date of the cut off date of 13 December 2016; follow-up for PFS was 21 months |
| Safety Issue: | |
| Description: | Progression-free survival was defined as the duration from the date of randomization to the date of disease progression (DP) based on investigator's assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 or death (from any cause), whichever occurred first. Per RECIST 1.1, progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions from nadir or appearance of a new lesion. |
Secondary Outcome Measures
| Measure: | Percentage of Participants Who Achieved a Confirmed Complete Response (CR) or Partial Response (PR) to Treatment (Objective Response Rate) Based On the Investigator Assessment |
| Time Frame: | Disease response was assessed every 8 weeks, for the first 24 weeks, then every 12 weeks until DP; from date of randomization of study drug to data cut-off date of 13 December 2016; follow-up for overall response was 21 months |
| Safety Issue: | |
| Description: | Overall response rate was defined as the percentage of participants who achieved a confirmed complete response or partial response based on RECIST Version 1.1 criteria. RECIST criteria v 1.1 defined a CR as the disappearance of all target lesions and a PR with at least a 30% decrease in the sum of diameters of target lesions from baseline. The two-sided 95% exact binomial CI for each arm was estimated by the Clopper-Pearson method. |
| Measure: | Percentage of Participants Who Achieved a Confirmed CR, PR or Stable Disease (SD) for ≥ 24 Weeks (Clinical Benefit Rate) by Investigator Assessment |
| Time Frame: | Disease response was assessed every 8 weeks, for the first 24 weeks, then every 12 weeks until DP; from date of randomization of study drug to the data cut-off date of 13 December 2016; follow-up for clinical benefit response was 21 months |
| Safety Issue: | |
| Description: | Percentage of participants with CR or PR or SD was defined per RECIST criteria v 1.1 as a CR that includes a disappearance of all target lesions, a PR was defined as having at least a 30% decrease in the sum of diameters of target lesions from baseline and SD as neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for progressive disease. The two-sided 95% exact binomial CI each arm was estimated by the Clopper-Pearson method. |
| Measure: | Kaplan Meier Estimate of Overall Survival |
| Time Frame: | From the date of randomization of study drug to the data cut off date of 13 December 2016; participants were followed for overall survival for 21 months |
| Safety Issue: | |
| Description: | Overall survival was defined as the time from the date of randomization to the date of death (from any cause). All participants who were lost to follow up prior to the end of the study or who were withdrawn from the study were censored at the time of last contact. |
| Measure: | Kaplan Meier Estimate of Duration of Response (DoR) |
| Time Frame: | From the date of randomization of study drug to the data cut-off of 13 December 2016; follow up for duration of response was 21 months |
| Safety Issue: | |
| Description: | Duration of response was defined as the time from the first tumor assessment when the confirmed CR/PR criterion was first met to the date of disease progression, based on investigator's assessment following RECIST Version 1.1 criteria. |
| Measure: | Number of Participants With Treatment Emergent Adverse Events (TEAEs) |
| Time Frame: | Randomization to 28 days after the last dose of IP; those AEs known at any time thereafter being related to IP; up to the last subject last visit of 21 November 2017; TEAE follow-up occurred up to 155 weeks and 2 days |
| Safety Issue: | |
| Description: | Treatment-emergent adverse events (TEAEs) were defined as any AEs that begin or worsen with an onset date on or after the date of the first dose of IP through 28 days after the last dose. A serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs were graded based on the participant's symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity as follows: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death. |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Terminated |
| Lead Sponsor: | Celgene |
Trial Keywords
- Breast Cancer
- Her2 -
- ER+
- CC-486 (ORAL AZACITIDINE)
- Metastatic Breast Cancer
- Oral Azacitidine
- Fulvestrant
- Epigenetics
Last Updated
December 14, 2018
