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

NCT ID: NCT02374099

Last Updated: 2018-12-14

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

97 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-03-13

Study Completion Date

2017-11-21

Brief Summary

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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

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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.

Conditions

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Breast Neoplasms

Keywords

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Breast Cancer Her2 - ER+ CC-486 (ORAL AZACITIDINE) Metastatic Breast Cancer Oral Azacitidine Fulvestrant Epigenetics

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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CC-486 and fulvestrant

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.

Group Type EXPERIMENTAL

CC-486

Intervention Type DRUG

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

Intervention Type DRUG

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.

Fulvestrant

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.

Group Type EXPERIMENTAL

Fulvestrant

Intervention Type DRUG

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.

Interventions

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CC-486

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

Intervention Type DRUG

Fulvestrant

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.

Intervention Type DRUG

Other Intervention Names

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Oral Azacitidine Faslodex

Eligibility Criteria

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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 \[defined as a sexually mature woman who (1) has not undergone hysterectomy (the surgical removal of the uterus) or bilateral oopherectomy (the surgical removal of both ovaries) or (2) has not been naturally postmenopausal for at least 12 consecutive months (ie, has had menses at any time during the preceding 12 consecutive months)\].
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Celgene

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ileana Elias, MD

Role: STUDY_DIRECTOR

Celgene

Locations

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Ironwood Cancer and Research Center

Chandler, Arizona, United States

Site Status

Virginia G Piper Cancer Center

Scottsdale, Arizona, United States

Site Status

Highlands Oncology Group

Fayetteville, Arkansas, United States

Site Status

Florida Cancer Specialists

West Palm Beach, Florida, United States

Site Status

University of Kansas Hospital

Westwood, Kansas, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Clinical Research Alliance

New York, New York, United States

Site Status

Medical Oncology Associates

Spokane, Washington, United States

Site Status

Grand Hopital de Charleroi

Charleroi, , Belgium

Site Status

AZ Groeninge

Kortrijk, , Belgium

Site Status

Clinique Sainte Elisabeth - Service d'Oncologie

Namur, , Belgium

Site Status

GasthuisZusters Antwerpen

Wilrijk, , Belgium

Site Status

Centre Regional de lutte contre le cancer Paul Papin

Angers, , France

Site Status

Institut Bergonie

Borddeaux Cedex, , France

Site Status

Hopital Pitie Salpetriere

Paris, , France

Site Status

Centre Rene Gauducheau Centre de Lutte Contre Le Cancer Nantes Atlantique

Saint-Herblain, , France

Site Status

Universitatsklinikum Hamburg-Eppendorf / IVDP

Hamburg, , Germany

Site Status

Hamatologisch Onkologische Praxis Eppendorf

Hamburg, , Germany

Site Status

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, , Germany

Site Status

TU München - Klinikum rechts der Isar

München, , Germany

Site Status

Policlinico S. Orsola - Malpighi

Bologna, , Italy

Site Status

Ospedale San Raffaele S.r.l.

Milan, , Italy

Site Status

Istituto Nazionale Dei Tumori

Milan, , Italy

Site Status

IEO- Istituto Europeo di Oncologia

Milan, , Italy

Site Status

Arcispedale Santa Maria Nuova

Reggio Emilia, , Italy

Site Status

Policlinico Umberto I

Roma, , Italy

Site Status

Policlinico Universitario A Gemelli

Roma, , Italy

Site Status

Azienda Ospedaliera Citta della Salute e della Scienza di Torino

Torino, Piemonte, , Italy

Site Status

Complejo Universitario La Coruna

A Coruña, , Spain

Site Status

Hospital del Mar

Barcelona, , Spain

Site Status

Hospital Universitario Vall D Hebron

Barcelona, , Spain

Site Status

Hospital General Gregorio Maranon

Madrid, , Spain

Site Status

Hospital Ramon y Cajal

Madrid, , Spain

Site Status

Hospital Clinico Universitario Virgen de La Victoria

Málaga, , Spain

Site Status

Hospital Virgen del Rocio

Seville, , Spain

Site Status

Countries

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United States Belgium France Germany Italy Spain

Other Identifiers

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CC-486-BRSTM-001

Identifier Type: -

Identifier Source: org_study_id