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NCT02374099

Study to Assess the Efficacy and Safety of the Epigenetic Modifying Effects of CC-486 (Oral Azacitidine) in Combination With Fulvestrant

Terminated Phase 2 Results posted Last updated 14 December 2018
What this trial tests

Phase 2 trial testing CC-486 in Breast Neoplasms in 97 participants. Terminated before completion.

Timeline
13 March 2015
Primary endpoint
13 December 2016
21 November 2017

Quick facts

Lead sponsorCelgene
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment97
Start date13 March 2015
Primary completion13 December 2016
Estimated completion21 November 2017
Sites35 locations across France, Italy, Belgium, Germany, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

Celgene — full company profile →

Who can join

18 and older, female only, with Breast Neoplasms. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Kaplan-Meier Estimate of Progression Free Survival (PFS) Primary · 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

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.

GroupValue95% CI
CC-486 and Fulvestrant5.492.07 – 8.25
Fulvestrant5.463.58 – 7.36
Percentage of Participants Who Achieved a Confirmed Complete Response (CR) or Partial Response (PR) to Treatment (Objective Response Rate) Based On the Investigator Assessment Secondary · 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

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.

GroupValue95% CI
CC-486 and Fulvestrant8.32.32 – 19.98
Fulvestrant2.00.05 – 10.85
Percentage of Participants Who Achieved a Confirmed CR, PR or Stable Disease (SD) for ≥ 24 Weeks (Clinical Benefit Rate) by Investigator Assessment Secondary · 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

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.

GroupValue95% CI
CC-486 and Fulvestrant31.318.66 – 46.25
Fulvestrant30.618.25 – 45.42
Kaplan Meier Estimate of Overall Survival Secondary · 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

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.

GroupValue95% CI
CC-486 and FulvestrantNA13.7 – NA
FulvestrantNA10.7 – NA
Kaplan Meier Estimate of Duration of Response (DoR) Secondary · 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

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.

GroupValue95% CI
CC-486 and FulvestrantNA6.61 – NA
FulvestrantNANA – NA
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Secondary · 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

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 Adve

TEAE
GroupValue95% CI
CC-486 and Fulvestrant46
Fulvestrant45
Grade 3 or 4 TEAE
GroupValue95% CI
CC-486 and Fulvestrant32
Fulvestrant15
Grade 5 TEAE (Death)
GroupValue95% CI
CC-486 and Fulvestrant2
Fulvestrant1
Serious TEAE
GroupValue95% CI
CC-486 and Fulvestrant10
Fulvestrant7
TEAE Leading to Stopping of Any IP
GroupValue95% CI
CC-486 and Fulvestrant14
Fulvestrant1
TEAE Leading to Dose Reduction of any IP
GroupValue95% CI
CC-486 and Fulvestrant19
Fulvestrant0
TEAE Leading to Dose Interruption of any IP
GroupValue95% CI
CC-486 and Fulvestrant22
Fulvestrant3
Treatment Related TEAE
GroupValue95% CI
CC-486 and Fulvestrant46
Fulvestrant31

Adverse events — posted to ClinicalTrials.gov

Time frame: From randomization date to 28 days after the last dose of IP; those AEs known at any time thereafter being related to IP; up to last subject last visit date of 21 November 2017.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

CC-486 and Fulvestrant
Serious: 10/46 (22%)
Deaths: 14/46
Fulvestrant
Serious: 7/48 (15%)
Deaths: 16/48

Serious adverse events (21 terms)

ReactionSystemCC-486 and FulvestrantFulvestrant
VomitingGastrointestinal disorders
NauseaGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Pericardial effusionCardiac disorders
ConstipationGastrointestinal disorders
Gastrointestinal necrosisGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
Chest painGeneral disorders
FatigueGeneral disorders
Hepatic failureHepatobiliary disorders
PneumoniaInfections and infestations
Hip fractureInjury, poisoning and procedural complications
Back painMusculoskeletal and connective tissue disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
Neck painMusculoskeletal and connective tissue disorders
Pathological fractureMusculoskeletal and connective tissue disorders
Spinal osteoarthritisMusculoskeletal and connective tissue disorders
Cervical myelopathyNervous system disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Other adverse events (37 terms — click to expand)

ReactionSystemCC-486 and FulvestrantFulvestrant
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
ConstipationGastrointestinal disorders
AstheniaGeneral disorders
FatigueGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
NeutropeniaBlood and lymphatic system disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Abdominal painGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
Bone painMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Injection site painGeneral disorders
Aspartate aminotransferase increasedInvestigations
HeadacheNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
Hot flushVascular disorders
Urinary tract infectionInfections and infestations
Muscle spasmsMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
InsomniaPsychiatric disorders
RashSkin and subcutaneous tissue disorders
AnaemiaBlood and lymphatic system disorders
Oedema peripheralGeneral disorders
PyrexiaGeneral disorders
Viral upper respiratory tract infectionInfections and infestations
Blood alkaline phosphatase increasedInvestigations
Weight decreasedInvestigations
White blood cell count decreasedInvestigations
HyperuricaemiaMetabolism and nutrition disorders
Musculoskeletal chest painMusculoskeletal and connective tissue disorders
AnxietyPsychiatric disorders

Most-reported serious reactions: Vomiting, Nausea, Dyspnoea, Anaemia, Pericardial effusion, Constipation, Gastrointestinal necrosis, Small intestinal obstruction.

Data from ClinicalTrials.gov NCT02374099 adverse events section.

Sponsor's own 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).

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Epigenetics in Breast Cancer Therapy-New Strategies and Future Nanomedicine Perspectives.
    Buocikova V, Rios-Mondragon I, Pilalis E, Chatziioannou A, et al · · 2020 · cited 42× · PMID 33287297 · DOI 10.3390/cancers12123622
  2. Epigenetic Therapies and Biomarkers in Breast Cancer.
    Brown LJ, Achinger-Kawecka J, Portman N, Clark S, et al · · 2022 · cited 33× · PMID 35158742 · DOI 10.3390/cancers14030474
  3. Harnessing Epigenetics for Breast Cancer Therapy: The Role of DNA Methylation, Histone Modifications, and MicroRNA.
    Szczepanek J, Skorupa M, Jarkiewicz-Tretyn J, Cybulski C, et al · · 2023 · cited 30× · PMID 37108398 · DOI 10.3390/ijms24087235
  4. Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions.
    Xia W, Jiang M, Huang Y, Ding K, et al · · 2026 · PMID 41929361 · DOI 10.1002/mco2.70655
  5. DNA methyltransferase inhibitors in oncology: clinical progress, limitations and future directions.
    Michael DC, Mehdipour P. · · 2026 · PMID 41762718 · DOI 10.1080/17501911.2026.2637418

Verify or expand the search:

Other trials of CC-486

Trials testing the same drug.

Other recruiting trials for Breast Neoplasms

Currently open trials in the same condition.

Other Celgene trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing