Clinical Trials /

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

NCT02374099

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).

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: CC-486-BRSTM-001
  • NCT ID: NCT02374099

Conditions

  • Breast Neoplasms

Interventions

DrugSynonymsArms
CC-486Oral AzacitidineCC-486 and fulvestrant
FulvestrantfoslodexCC-486 and fulvestrant

Purpose

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 ER+, HER2- Metastatic Breast Cancer Who Have Progressed on an Aromatase Inhibitor.

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 subjects 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.
    

Trial Arms

NameTypeDescriptionInterventions
CC-486 and fulvestrantExperimentalCC-486 300mg 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.
  • CC-486
  • Fulvestrant
FulvestrantExperimentalFulvestrant 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

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)].
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Time period of progression free survival of patients in the combination arm versus the Fulvestrant only arm.
Time Frame:approximately 21 months
Safety Issue:
Description:Estimation of the hazard ratio of PFS of the combination arm relative to fulvestrant monotherapy arm

Secondary Outcome Measures

Measure:Overall Response Rate
Time Frame:Approximately 28 months
Safety Issue:
Description:The combined incidence of CR and PR, confirmed no less than 4 weeks after the criteria for response are first met, based on RECIST Version 1.1
Measure:Complete Benefit Rate
Time Frame:Approximately 28 months
Safety Issue:
Description:Complete response (CR) + PR + SD ( ≥ 24 weeks)
Measure:Overall Survival
Time Frame:Approximately 28 months
Safety Issue:
Description:Overall Survival (OS): time from date of randomization to date of death due to any cause.
Measure:Response Duration
Time Frame:Approximately 28 months
Safety Issue:
Description:Duration of response in subjects with a confirmed objective CR or PR
Measure:Adverse Events
Time Frame:Approximately 28 months
Safety Issue:
Description:incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), Grade 3 and higher AEs, AEs of special interest, and laboratory abnormalities and other safety parameters

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Celgene

Trial Keywords

  • Breast Cancer
  • Her2 -
  • ER+
  • CC-486 (ORAL AZACITIDINE)
  • Metastatic Breast Cancer
  • Oralazacitidine
  • Fulvestrant
  • Epigenetics

Last Updated

November 27, 2017