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

NCT02374099 | Terminated Phase 2 Results DMC

• 1 other identifier: CC-486-BRSTM-001
• Study Type: interventional
• Target: 97
• Locations: 6 countries
• Sites: 35

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).

Conditions

Breast Neoplasms

Keywords

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

Outcome Measures

Primary Outcomes (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.

  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)

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

  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

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

  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

• Kaplan Meier Estimate of Overall Survival

  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

• Kaplan Meier Estimate of Duration of Response (DoR)

  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

• Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  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

Study Arms (2)

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.

Drug: CC-486; Drug: Fulvestrant

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.

Drug: Fulvestrant

Interventions

CC-486 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

Also known as: Oral Azacitidine

CC-486 and fulvestrant

Fulvestrant 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.

Also known as: Faslodex

CC-486 and fulvestrant; Fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Celgene: lead

Study Sites (35)

Ironwood Cancer and Research Center

Chandler, Arizona, 85224, United States

Location

Virginia G Piper Cancer Center

Scottsdale, Arizona, 85258, United States

Location

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

Florida Cancer Specialists

West Palm Beach, Florida, 33401, United States

Location

University of Kansas Hospital

Westwood, Kansas, 66205, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Clinical Research Alliance

New York, New York, 10021, United States

Location

Medical Oncology Associates

Spokane, Washington, 99208, United States

Location

Grand Hopital de Charleroi

Charleroi, 6000, Belgium

Location

AZ Groeninge

Kortrijk, 8500, Belgium

Location

Clinique Sainte Elisabeth - Service d'Oncologie

Namur, 5000, Belgium

Location

GasthuisZusters Antwerpen

Wilrijk, 2610, Belgium

Location

Centre Regional de lutte contre le cancer Paul Papin

Angers, 49933, France

Location

Institut Bergonie

Borddeaux Cedex, 33076, France

Location

Hopital Pitie Salpetriere

Paris, 75651, France

Location

Centre Rene Gauducheau Centre de Lutte Contre Le Cancer Nantes Atlantique

Saint-Herblain, 44805, France

Location

Universitatsklinikum Hamburg-Eppendorf / IVDP

Hamburg, 20246, Germany

Location

Hamatologisch Onkologische Praxis Eppendorf

Hamburg, 20249, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

Location

TU München - Klinikum rechts der Isar

München, 81675, Germany

Location

Policlinico S. Orsola - Malpighi

Bologna, 40138, Italy

Location

Ospedale San Raffaele S.r.l.

Milan, 20132, Italy

Location

Istituto Nazionale Dei Tumori

Milan, 20133, Italy

Location

IEO- Istituto Europeo di Oncologia

Milan, 20144, Italy

Location

Arcispedale Santa Maria Nuova

Reggio Emilia, 42100, Italy

Location

Policlinico Umberto I

Roma, 00161, Italy

Location

Policlinico Universitario A Gemelli

Roma, 00168, Italy

Location

Azienda Ospedaliera Citta della Salute e della Scienza di Torino

Torino, Piemonte, 10126, Italy

Location

Complejo Universitario La Coruna

A Coruña, 15006, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitario Vall D Hebron

Barcelona, 8035, Spain

Location

Hospital General Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Clinico Universitario Virgen de La Victoria

Málaga, 29011, Spain

Location

Hospital Virgen del Rocio

Seville, 41013, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

cc-486; Azacitidine; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Clinical Trial Disclosure
• Organization: Celgene Corporation

ClinicalTrialDisclosure@Celgene.com

888-260-1599

Study Officials

• Ileana Elias, MD

  Celgene

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: January 22, 2015
• First Posted: February 27, 2015
• Study Start: March 13, 2015
• Primary Completion: December 13, 2016
• Study Completion: November 21, 2017
• Last Updated: December 14, 2018
• Results First Posted: December 14, 2018

Record last verified: 2018-12

Locations

IT (8); ES (7); US (8); DE (4); FR (4); BE (4)