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Breast CancerPhase 2ENCORE305NCT02115594

Phase 2 Study of Fulvestrant With and Without Entinostat in Postmenopausal Women With ER+ Advanced Breast Cancer

A Phase 2 study testing Fulvestrant and Entinostat in people with Breast Cancer, run by Syndax Pharmaceuticals at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

Preclinical data has demonstrated that entinostat (SNDX-275) can enhance fulvestrant sensitivity in hormone receptor-positive breast cancer in animal models. The addition of entinostat to fulvestrant will provide clinical benefit to patients with locally advanced or metastatic breast when compared to fulvestrant plus… Read more about this study

Who is it for?
Any age, women only
Conditions the study is for
Breast Cancer
What is being tested?
Fulvestrant and Entinostat
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
1 siteUnited States
Study dates
Apr 2014to Jun 2016
Phase
Phase 2
Are there results?
None posted in the registry

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 Any age
  • Women only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patient is a female who is: Postmenopausal OR Pre/perimenopausal and: Received at least one prior hormone therapy in combination with a luteinizing hormone-releasing hormone (LHRH) agonist prior to study entry. Initiated on an LHRH agonist at least 28 days prior to study entry. Demonstrated ovarian estradiol suppression, defined as an estradiol level within postmenopausal ranges per institutional guidelines, within 28 days immediately prior to study entry
  • Patient has histologically or cytologically confirmed ER+ and/or progesterone receptor-positive (PR+) BC at initial diagnosis or on subsequent biopsy. With regard to hormone receptor status, staining of ≥1% cells is considered positive. Receptor status may have been determined at any time prior to randomization and from any site (i.e., primary, recurrent, or metastatic)
  • Patient experienced PD within 28 days before initiating study treatment and has been deemed eligible for treatment with fulvestrant
  • Patient has evidence of locally advanced or metastatic disease, based on imaging studies (bone scan, CT, MRI) within 28 days before initiating study treatment
  • Patient completed any prior radiotherapy ≥2 weeks prior to receiving the first dose of study treatment and has recovered from any radiation-related toxicity
  • Patient may have received 1 prior chemotherapy regimen for metastatic disease provided treatment was completed ≥3 weeks prior to randomization. Prior chemotherapy in the adjuvant or neoadjuvant setting is also allowed
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  • Patient is willing and able to provide or assist study personnel in accessing slides from prior biopsies
  • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Patient has the following laboratory parameters: a. Hemoglobin (Hgb) ≥9.0 g/dL; unsupported platelet count ≥100×10P9P/L; and absolute neutrophil count (ANC) ≥1.5×10P9P/L without the use of hematopoietic growth factors; b. Creatinine ≤2.0 mg/dL; c. Total bilirubin <1.5 x institutional upper limit normal (≤3 mg/dL in case of Gilbert's syndrome); d. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2 x institutional upper limit of normal; unless elevation is due to metastatic disease to the liver, in which case ALT and AST must be within 5.0 x institutional upper limit of normal
  • Patient is able to swallow tablets
  • Patient is able to understand and give written informed consent and comply with study procedures

Who cannot join

  • Patient has rapidly progressive or life-threatening metastases (visceral crisis)
  • Patient has HER2-positive (HER2+) disease, as defined by the 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) recommendations for HER2 testing in BC (see http://www.asco.org/quality-guidelines/recommendations-human-epidermal-growth-factor-receptor-2-testing-breast-cancer), or has unknown HER2 status
  • Patient previously received treatment with entinostat or any other HDAC inhibitor, including valproic acid
  • Patient has had previous treatment with fulvestrant or other selective estrogen receptor down-regulator (SERD) in the metastatic setting; such treatment may have been given in the adjuvant setting
  • Patient has an allergy to benzamide or inactive components of the study drug
  • Patient has a history of allergies to any active or inactive ingredients of fulvestrant
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  • Patient has a concomitant medical condition that precludes adequate study treatment compliance or assessment, or increases patient risk, in the opinion of the Investigator, such as but not limited to:
  • Myocardial infarction or arterial thromboembolic event within 6 months prior to Baseline or severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease (see Appendix 2), or a QTc interval >470 msec.
  • Uncontrolled heart failure or hypertension, uncontrolled diabetes mellitus, or uncontrolled systemic infection
  • Another active cancer (excluding adequately treated basal cell carcinoma or cervical intraepithelial neoplasia [CIN] / cervical carcinoma in situ or melanoma in situ). Prior history of other cancer is allowed, as long as there is no active disease within the prior 5 years
  • Patient is currently receiving treatment with any agent listed on the prohibited medication list such as valproic acid or other systemic cancer agents
  • Patient initiated oral bisphosphonates within 7 days prior to study drug
  • Patient has moderate or severe hepatic impairment (i.e., Child-Pugh score B or C)
  • Patient has brain or leptomeningeal metastases

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Tennessee Oncololgy

    Nashville, Tennessee, 37203

Other trials in United States

About this study

Official title: A Phase 2, Randomized, Double-Blind, Multicenter Study of Fulvestrant With and Without Entinostat in Postmenopausal Women With Hormone Receptor-Positive Advanced Breast Cancer

Preclinical data has demonstrated that entinostat (SNDX-275) can enhance fulvestrant sensitivity in hormone receptor-positive breast cancer in animal models. The addition of entinostat to fulvestrant will provide clinical benefit to patients with locally advanced or metastatic breast when compared to fulvestrant plus placebo. Also, based on previous data, patients exposed to entinostat who demonstrate an elevated level of protein lysine acetylation will have an improved efficacy outcome.

Read the detailed description

Entinostat (SNDX-275) inhibits mechanisms of resistance to hormone therapy in breast cancer (BC) cells, thereby prolonging sensitivity of the cells to fulvestrant. Preclinical data has demonstrated that entinostat can enhance fulvestrant sensitivity in hormone receptor-positive BC in animal models. Thus, it is hypothesized that the addition of entinostat to fulvestrant will provide clinical benefit to patients with locally advanced or metastatic BC when compared to fulvestrant plus placebo.

Preliminary data from Phase 2 Study SNDX-275-0301 suggest patients with higher levels of protein lysine acetylation who receive entinostat with exemestane potentially have improved clinical outcomes (e.g., PFS, OS) when compared to patients with lower levels of protein lysine acetylation. Thus, it is hypothesized that patients exposed to entinostat and who demonstrate an elevated level of protein lysine acetylation will have an improved efficacy outcome.

Conditions
Breast Cancer
Being tested
Fulvestrant, Entinostat, Placebo
Keywords
metastatic breast cancer, estrogen receptor, Histone Deacetylase Inhibitors, Histone Deacetylases, HDAC inhibitors, selective estrogen receptor modulator, estrogen receptor modulator, selective, Estrogen receptor modulators, selective
Medical subject headings
Breast Neoplasms

What participants receive

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

  • FulvestrantDrug

    Also called faslodex

  • EntinostatDrug

  • PlaceboDrug

Study groups in NCT02115594
Study groupRoleWhat they receive
Fulvestrant + EntinostatExperimentalArm A: Fulvestrant (500 mg on C1D1, C1D15, C2D1, and on Day 1 of each subsequent cycle) plus entinostat (5 mg PO once weekly)
Receives: Drug: Fulvestrant; Drug: Entinostat
Fulvestrant + PlaceboActive comparatorArm B: Fulvestrant (500 mg on C1D1, C1D15, C2D1, and on Day 1 of each subsequent cycle) plus placebo (5 mg PO once weekly)
Receives: Drug: Fulvestrant; Drug: Placebo

What is being measured

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

  1. Progression Free Survival

    Radiological disease assessments

    Measured: From date of randomization until the date of 1st documented progression or date of death from any cause, whichever occurs first, assessed for up to 48 months

Secondary outcomes (6)

  1. Objective Response Rate (CR or PR)

    Radiological disease assessments

    Measured: From date of randomization until the date of 1st documented progression or date of death from any cause, whichever occurs first, for up to 48 months

  2. Clinical Benefit Rate (CR, PR, or SD for greater than or equal to 6 months from randomization)

    Radiological disease assessments

    Measured: From the date of randomization until the date of 1st documented progression or date of death, from any cause, whichever occurs first, assessed for up to 48 months

  3. Overall Survival

    Measured: From the date of randomization until date of death, assessed for up to 48 months

  4. Clinical review of safety parameters (AEs, lab values)

    Measured: From date of randomization until 30 days post the date of study treatment discontinuation

  5. Percent change from baseline in blood protein lysine acetylation measures

    Measured: From the baseline visit through the 1st 15 days of study treatment

  6. Concentrations of entinostat measured in plasma (PK)

    Measured: From the baseline visit through the 1st 15 days of study treatment

Timeline

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

  1. First posted16 Apr 2014 (estimated)
  2. Study startApr 2014
  3. Primary completionDec 2015 (estimated)
  4. Study completionJun 2016 (estimated)

Why it stopped: Internal decision

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
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02115594
Sponsor's protocol ID
SNDX-275-0305
Acronym
ENCORE305
Status last verified
Apr 2014
First submitted
4 Apr 2014
Last updated
8 Oct 2014
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fulvestrant and Entinostat in people with Breast Cancer, run by Syndax Pharmaceuticals at 1 site in United States.

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 11 inclusion and 14 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: withdrawn, as of the sponsor's last update on 8 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Progression Free Survival (time frame: From date of randomization until the date of 1st documented progression or date of death from any cause, whichever occurs first, assessed for up to 48 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 NCT02115594.

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 8 Oct 2014.

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