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Breast NeoplasmsPhase 2NCT02374099

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

A Phase 2 study testing CC-486 and Fulvestrant in people with Breast Neoplasms, run by Celgene at 35 sites in 6 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Neoplasms
What is being tested?
CC-486 and Fulvestrant
Could I receive a placebo?
No, everyone receives an active treatment
How many people
97 participants
Where
35 sitesin 6 countries
Study dates
13 Mar 2015to 21 Nov 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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).
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  • 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)].

Trial locations and contacts

35 sites in 6 countries.

35 sites in 6 countries

United States8 sites

  • Ironwood Cancer and Research Center

    Chandler, Arizona, 85224

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • Highlands Oncology Group

    Fayetteville, Arkansas, 72703

  • Clinical Research Alliance

    New York, New York, 10021

  • Virginia G Piper Cancer Center

    Scottsdale, Arizona, 85258

  • Medical Oncology Associates

    Spokane, Washington, 99208

  • Florida Cancer Specialists

    West Palm Beach, Florida, 33401

  • University of Kansas Hospital

    Westwood, Kansas, 66205

Other trials in United States

Italy8 sites

  • Policlinico S. Orsola - Malpighi

    Bologna, 40138

  • Ospedale San Raffaele S.r.l.

    Milan, 20132

  • Istituto Nazionale Dei Tumori

    Milan, 20133

  • IEO- Istituto Europeo di Oncologia

    Milan, 20144

  • Arcispedale Santa Maria Nuova

    Reggio Emilia, 42100

  • Policlinico Umberto I

    Roma, 00161

  • Policlinico Universitario A Gemelli

    Roma, 00168

  • Azienda Ospedaliera Citta della Salute e della Scienza di Torino

    Torino, Piemonte, 10126

Other trials in Italy

Spain7 sites

  • Complejo Universitario La Coruna

    A Coruña, 15006

  • Hospital del Mar

    Barcelona, 08003

  • Hospital Universitario Vall D Hebron

    Barcelona, 8035

  • Hospital General Gregorio Maranon

    Madrid, 28007

  • Hospital Ramon y Cajal

    Madrid, 28034

  • Hospital Clinico Universitario Virgen de La Victoria

    Málaga, 29011

  • Hospital Virgen del Rocio

    Seville, 41013

Other trials in Spain

Belgium4 sites

  • Grand Hopital de Charleroi

    Charleroi, 6000

  • AZ Groeninge

    Kortrijk, 8500

  • Clinique Sainte Elisabeth - Service d'Oncologie

    Namur, 5000

  • GasthuisZusters Antwerpen

    Wilrijk, 2610

Other trials in Belgium

France4 sites

  • Centre Regional de lutte contre le cancer Paul Papin

    Angers, 49933

  • Institut Bergonie

    Borddeaux Cedex, 33076

  • Hopital Pitie Salpetriere

    Paris, 75651

  • Centre Rene Gauducheau Centre de Lutte Contre Le Cancer Nantes Atlantique

    Saint-Herblain, 44805

Other trials in France

Germany4 sites

  • Universitatsklinikum Hamburg-Eppendorf / IVDP

    Hamburg, 20246

  • Hamatologisch Onkologische Praxis Eppendorf

    Hamburg, 20249

  • Universitätsmedizin der Johannes Gutenberg-Universität Mainz

    Mainz, 55131

  • TU München - Klinikum rechts der Isar

    München, 81675

Other trials in Germany

About this study

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

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).

Read the 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.

Being tested
CC-486, Fulvestrant
Keywords
Breast Cancer, Her2 -, ER+, CC-486 (ORAL AZACITIDINE), Metastatic Breast Cancer, Oral Azacitidine, Fulvestrant, Epigenetics
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CC-486Drug

    Also called Oral Azacitidine

    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

  • FulvestrantDrug

    Also called Faslodex

    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.

Study groups in NCT02374099
Study groupRoleWhat they receive
CC-486 and fulvestrantExperimentalCC-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.
Receives: Drug: CC-486; Drug: Fulvestrant
FulvestrantExperimentalFulvestrant 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.
Receives: Drug: Fulvestrant

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Kaplan-Meier Estimate of Progression Free Survival (PFS)

    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.

    Measured: 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

Secondary outcomes (5)

  1. Percentage of Participants Who Achieved a Confirmed Complete Response (CR) or Partial Response (PR) to Treatment (Objective Response Rate) Based On the Investigator Assessment

    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.

    Measured: 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

  2. Percentage of Participants Who Achieved a Confirmed CR, PR or Stable Disease (SD) for ≥ 24 Weeks (Clinical Benefit Rate) by Investigator Assessment

    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.

    Measured: 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

  3. Kaplan Meier Estimate of Overall Survival

    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.

    Measured: 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

  4. Kaplan Meier Estimate of Duration of Response (DoR)

    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.

    Measured: 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

  5. Number of Participants With Treatment Emergent Adverse Events (TEAEs)

    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.

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Feb 2015 (estimated)
  2. Study start13 Mar 2015
  3. Primary completion13 Dec 2016
  4. Study completion21 Nov 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
97 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02374099
Sponsor's protocol ID
CC-486-BRSTM-001
Status last verified
Dec 2018
First submitted
22 Jan 2015
Last updated
14 Dec 2018
Data monitoring committee
Yes
Expanded access
Available

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CC-486 and Fulvestrant in people with Breast Neoplasms, run by Celgene at 35 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 35 sites in United States, Italy, Spain, Belgium, France and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02374099.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2018.

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