Clinical trial NCT02374099: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Neoplasms
Keywords: Breast Cancer
Her2 -
ER+
CC-486 (ORAL AZACITIDINE)
Metastatic Breast Cancer
Oral Azacitidine
Fulvestrant
Epigenetics
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2015-02-27
Enrollment: 97
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 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.

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

Primary outcomes:
measure: Kaplan-Meier Estimate of Progression Free Survival (PFS)
timeFrame: 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:
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
timeFrame: 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
measure: Percentage of Participants Who Achieved a Confirmed CR, PR or Stable Disease (SD) for ≥ 24 Weeks (Clinical Benefit Rate) by Investigator Assessment
timeFrame: 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
measure: Kaplan Meier Estimate of Overall Survival
timeFrame: 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
measure: Kaplan Meier Estimate of Duration of Response (DoR)
timeFrame: 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
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: 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
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Ironwood Cancer and Research Center
state: Arizona
city: Scottsdale
country: United States
facility: Virginia G Piper Cancer Center
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Westwood
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: New York
country: United States
facility: Clinical Research Alliance
state: New York
city: Spokane
country: United States
facility: Medical Oncology Associates
state: Washington
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Namur
country: Belgium
facility: Clinique Sainte Elisabeth - Service d'Oncologie
city: Wilrijk
country: Belgium
facility: GasthuisZusters Antwerpen
city: Angers
country: France
facility: Centre Regional de lutte contre le cancer Paul Papin
city: Borddeaux Cedex
country: France
facility: Institut Bergonie
city: Paris
country: France
facility: Hopital Pitie Salpetriere
city: Saint Herblain
country: France
facility: Centre Rene Gauducheau Centre de Lutte Contre Le Cancer Nantes Atlantique
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg-Eppendorf / IVDP
city: Hamburg
country: Germany
facility: Hamatologisch Onkologische Praxis Eppendorf
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz
city: München
country: Germany
facility: TU München - Klinikum rechts der Isar
city: Bologna
country: Italy
facility: Policlinico S. Orsola - Malpighi
city: Milano
country: Italy
facility: Ospedale San Raffaele S.r.l.
city: Milano
country: Italy
facility: Istituto Nazionale Dei Tumori
city: Milano
country: Italy
facility: IEO- Istituto Europeo di Oncologia
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova
city: Roma
country: Italy
facility: Policlinico Umberto I
city: Roma
country: Italy
facility: Policlinico Universitario A Gemelli
city: Torino, Piemonte
country: Italy
facility: Azienda Ospedaliera Citta della Salute e della Scienza di Torino
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitario Vall D Hebron
city: La Coruna
country: Spain
facility: Complejo Universitario La Coruna
city: Madrid
country: Spain
facility: Hospital General Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de La Victoria
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
Study officials:
affiliation: Celgene
name: Ileana Elias, MD
role: STUDY_DIRECTOR
References: