ER+ Breast CancerPhase 2NCT00828854
Study of the Effect of the Addition of SNDX-275 (Entinostat) to Continued Aromatase Inhibitor (AI) Therapy in Postmenopausal Women With ER+ Breast Cancer Whose Disease is Progressing
A Phase 2 study testing Entinostat and Aromatase Inhibitor (AI) Therapy in people with ER+ Breast Cancer, run by Syndax Pharmaceuticals at 6 sites in 2 countries.
Trial summary
The addition of entinostat to an AI will result in a maximal abrogation of estrogen receptor-α mediated activity and inhibit mechanisms of resistance to the aromatase inhibitor. It is hypothesized that entinostat with continued AI will increase the estimated AI clinical benefit rate (CBR) from 5% to 25% with an… Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- ER+ Breast Cancer
- What is being tested?
- Entinostat and Aromatase Inhibitor (AI) Therapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 1 Oct 2008to 24 Nov 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Postmenopausal female patients.
- Histologically or cytologically confirmed estrogen receptor-positive (ER+) breast cancer.
- Progressive disease (PD) after at least 3 months on treatment with a 3rd generation AI in the advanced disease setting as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
- At least 1 measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral computed tomography (CT) scan with the last imaging performed within 4 weeks prior to study entry. If there is only one measurable lesion and it is located in previously irradiated field, it must have demonstrated progression according to RECIST criteria.
- Eastern Cooperative Oncology Group (ECOG) 0-1.
- Laboratory parameters:
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- Hemoglobin ≥ 9.0 g/dL; platelets ≥ 100 x10^9/L; absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L without the use of hematopoietic growth factors.
- Creatinine less than 2.5 times the upper limit of normal for the institution.
- aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5 times the upper limit of normal for the institution.
- Able to understand and give written informed consent and comply with study procedures.
Who cannot join
- Discontinuation of AI therapy prior to study entry.
- Less than 3 months treatment with most recent AI.
- Rapidly progressive, life-threatening metastases, including any of the following:
- Symptomatic lymphangitic metastases.
- Patients with known active brain or leptomeningeal involvement.
- More than one prior chemotherapy for metastatic disease.
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- Any chemotherapy within 3 months prior to study.
- Radiotherapy to measurable lesion within 2 months prior to study.
- Bisphosphonates initiated within 4 weeks prior to study start.
- Allergy to benzamides or inactive components of study drug.
- Previous treatment with entinostat or any other histone deacetylase (HDAC) inhibitor including valproic acid.
- Patient is currently receiving treatment with any agent listed on the prohibited medication list such as valproic acid or other systemic cancer agents
- Any concomitant medical condition that precludes adequate study treatment compliance or assessment, or increases patient risk in the opinion of the investigator:
- Myocardial infarction or arterial thromboembolic events within 6 months, or experiencing severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease and a QTc interval >0.47 second.
- Uncontrolled heart failure or hypertension, uncontrolled diabetes mellitus, uncontrolled systemic infection,
- Other active malignancy within 5 years excluding basal cell carcinoma or cervical intraepithelial neoplasia [CIN / cervical carcinoma in situ] or melanoma in situ).
- Patient currently is enrolled in (or completed within 30 days before study drug administration) another investigational drug study.
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
United Kingdom5 sites
The University of Birmingham
Birmingham
Velindre Hospital - Whitchurch
Cardiff
Whiston Hospital; Clatterbridge Centre for Oncology
Liverpool
University College London Hospitals
London
Christie Hospital, Manchester Breast Centre
Manchester
About this study
Official title: A Phase 2 Multicenter Study of the Effect of the Addition of SNDX-275 to Continued Aromatase Inhibitor (AI) Therapy in Postmenopausal Women With ER+ Breast Cancer Whose Disease is Progressing
The addition of entinostat to an AI will result in a maximal abrogation of estrogen receptor-α mediated activity and inhibit mechanisms of resistance to the aromatase inhibitor.
It is hypothesized that entinostat with continued AI will increase the estimated AI clinical benefit rate (CBR) from 5% to 25% with an acceptable safety profile.
- Conditions
- ER+ Breast Cancer
- Being tested
- Entinostat, Aromatase Inhibitor (AI) Therapy
- Keywords
- breast cancer, estrogen receptor positive
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EntinostatDrug
Also called SNDX-275
Entinostat 5 mg PO every week
Aromatase Inhibitor (AI) TherapyDrug
AI therapy at labeled dose and schedule as prescribed in clinical practice. AI therapies include: Arimidex® (anastrozole) 1 mg/day by mouth (PO), Fermara® (letrozole) 2.5 mg/day PO , Aromasin® (exemestane) 25 mg/day PO.
| Study group | Role | What they receive |
|---|---|---|
| Entinostat 5 mg + AI | Experimental | Entinostat 5 mg tablet orally every week on Days 1, 8. 15 and 22 of each 28-day treatment cycle in combination with continued treatment with AI therapy at labeled dose and schedule until disease progression or unacceptable toxicity. Receives: Drug: Entinostat; Drug: Aromatase Inhibitor (AI) Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Benefit Rate (CBR)
CBR is defined as the percentage of participants who achieved complete response (CR) or partial response (PR) or stable disease (SD) for 6 months as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0. CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started.
Measured: 6 months
Secondary outcomes (3)
Progression-Free Survival (PFS)
PFS is defined as the number of months from the date of randomization to the earlier of progressive disease (PD) or death due to any cause.
Measured: Up to 6, 28-day cycles
Objective Response Rate (ORR) During the First 6 Cycles of Study Treatment
ORR is defined as the percentage of participants with response during treatment classified as CR or PR, as assessed by the investigator based on RECIST, version 1.0. CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.
Measured: Up to 6, 28-day cycles
Number of Participants With Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Worsening of a pre-existing medical condition was considered an AE if there was either an increase in severity, frequency, or duration of the condition or an association with significantly worse outcomes. Abnormal clinical laboratory findings determined by the investigator to be clinically significant were recorded as AEs.
Measured: Up to 6, 28-day cycles + 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2009 (estimated)
- Study start1 Oct 2008
- Primary completion24 Nov 2009
- Study completion24 Nov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for ER+ Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Syndax Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00828854
- Sponsor's protocol ID
- SNDX-275-0303
- Status last verified
- Jun 2022
- First submitted
- 23 Jan 2009
- Last updated
- 30 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Multicenter Study of the Effect of the Addition of SNDX-275 to Continued Aromatase Inhibitor (AI) Therapy in Postmenopausal Women With ER+ Breast Cancer Whose Disease is Progressing
- ClinicalTrials.gov ID
- NCT00828854
- Acronym / sponsor ID
- SNDX-275-0303
- Conditions
- ER+ Breast Cancer
- Keywords
- breast cancer, estrogen receptor positive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Syndax PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 1 Oct 2008 (actual)
- Primary completion
- 24 Nov 2009 (actual)
- Study completion
- 24 Nov 2009 (actual)
- First posted
- 26 Jan 2009 (estimated)
- Results
- Posted 30 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The addition of entinostat to an AI will result in a maximal abrogation of estrogen receptor-α mediated activity and inhibit mechanisms of resistance to the aromatase inhibitor.
It is hypothesized that entinostat with continued AI will increase the estimated AI clinical benefit rate (CBR) from 5% to 25% with an acceptable safety profile.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Entinostat 5 mg + AI | Experimental | Drug: Entinostat, Drug: Aromatase Inhibitor (AI) TherapyEntinostat 5 mg tablet orally every week on Days 1, 8. 15 and 22 of each 28-day treatment cycle in combination with continued treatment with AI therapy at labeled dose and schedule until disease progression or unacceptable toxicity. |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Postmenopausal female patients.
- Histologically or cytologically confirmed estrogen receptor-positive (ER+) breast cancer.
- Progressive disease (PD) after at least 3 months on treatment with a 3rd generation AI in the advanced disease setting as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
- At least 1 measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral computed tomography (CT) scan with the last imaging performed within 4 weeks prior to study entry. If there is only one measurable lesion and it is located in previously irradiated field, it must have demonstrated progression according to RECIST criteria.
- Eastern Cooperative Oncology Group (ECOG) 0-1.
Key exclusion criteria (17 listed)
- Discontinuation of AI therapy prior to study entry.
- Less than 3 months treatment with most recent AI.
- Rapidly progressive, life-threatening metastases, including any of the following:
- More than one prior chemotherapy for metastatic disease.
- Any chemotherapy within 3 months prior to study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EntinostatAlso: SNDX-275Entinostat 5 mg PO every week | Drug | Entinostat 5 mg + AI |
| Aromatase Inhibitor (AI) TherapyAI therapy at labeled dose and schedule as prescribed in clinical practice. AI therapies include: Arimidex® (anastrozole) 1 mg/day by mouth (PO), Fermara® (letrozole) 2.5 mg/day PO , Aromasin® (exemestane) 25 mg/day PO. | Drug | Entinostat 5 mg + AI |
Primary outcome
Clinical Benefit Rate (CBR)
Time frame: 6 months
CBR is defined as the percentage of participants who achieved complete response (CR) or partial response (PR) or stable disease (SD) for 6 months as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0. CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started.
3 secondary outcomes
Progression-Free Survival (PFS)
Time frame: Up to 6, 28-day cycles
Objective Response Rate (ORR) During the First 6 Cycles of Study Treatment
Time frame: Up to 6, 28-day cycles
Number of Participants With Adverse Events (AEs)
Time frame: Up to 6, 28-day cycles + 30 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Entinostat and Aromatase Inhibitor (AI) Therapy in people with ER+ Breast Cancer, run by Syndax Pharmaceuticals at 6 sites in 2 countries.
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 10 inclusion and 17 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: finished, as of the sponsor's last update on 30 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United Kingdom, Ireland. 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?
Yes. Results are posted in the registry (first posted 30 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Clinical Benefit Rate (CBR) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Jun 2022.