A Phase 2, Randomized, Double-Blind, Multicenter Study of Exemestane With and Without SNDX-275 in Postmenopausal Women with Locally Recurrent or Metastatic Estrogen Receptor-Positive Breast Cancer, Progressing on Treatment with a Non-Steroidal Aromatase Inhibitor

• Conditions: ER+ Breast Cancer; MedDRA version: 9.1Level: LLTClassification code 10006187Term: Breast cancer

• Registration Number: EUCTR2009-012623-28-CZ
• Lead Sponsor: Syndax Pharmaceuticals Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-06-18
• Last Update Posted: 30 September 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 130

Inclusion Criteria

1. Postmenopausal female patients

2. Histologically or cytologically confirmed ER+ breast cancer at initial diagnosis, with current disease relapse or progression that occurred while receiving a non-steroidal aromatase inhibitor (anastrozole Arimidex®” or letrozole Femara®”), meeting either of the following criteria

a. Relapse on non-steroidal AI given as adjuvant AI after at least 12 months treatment with the AI

OR

b. Progressive disease on prior non-steroidal AI after at least 3 months of treatment in the advanced disease setting

3. Evidence of metastatic disease based on imaging studies (bone scan, CT, MRI ):

a. Patients with bone only metastases are eligible provided there is a positive bone scan confirmed with MRI or PET-CT, according to local standard of care, within 4 weeks prior to study entry.

OR
b At least 1 measurable lesion = 20 mm by conventional techniques or = 10 mm by spiral 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.

4. Non-steroidal aromatase inhibitor (anastrozole Arimidex®” or letrozole Femara®”) treatment was the last systemic cancer therapy

5. Patients receiving palliative radiation at the non-target lesions must have a 2 week wash out period following completion of the treatment prior to receiving the first dose of study treatment

6. Patient may have had one prior chemotherapy in the metastatic setting as long as it was received before initiation of the most recent non-steroidal AI on which they progressed

7. ECOG performance status: 0 to 1 (Appendix 2)

8. Laboratory parameters:

a. Hemoglobin = 9.0 g/dL; platelets = 100.0 x 109/L; ANC = 1.5 x 109/L without the use of hematopoietic growth factors

b. Creatinine less than 2.5 times the upper limit of normal for the institution

c. AST and ALT less than 2.5 times the upper limit of normal for the institution

9. Able to understand and give written informed consent and comply with study procedures

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Discontinued non-steroidal aromatase inhibitor treatment for reasons other than relapse or progression

2. Received treatment with other cancer therapy(ies) following the last non-steroidal aromatase inhibitor therapy

3. Relapse on treatment with non-steroidal AI after less than 12 months for patients in the adjuvant setting

4. Progressive disease after less than 3 months treatment with most recent non-steroidal AI for patients with metastatic disease

5. Rapidly progressive, life-threatening metastases, including any of the following:

a. Symptomatic lymphangitic metastases

b. Symptomatic CNS involvement or untreated or unstable CNS metastasis, or having taken steroids for such condition within 28 days of the first dose of study treatment

6. Previous treatment with entinostat or any other HDAC inhibitor including valproic acid

7. Previous treatment with exemestane (Aromasin®) and or fulvestrant (Faslodex ®)

8. Allergy to benzamides or inactive components of the study drug

9. A history of allergies to any active or inactive ingredients of exemestane

10. Any concomitant medical condition that precludes adequate study treatment compliance or assessment, or increases patient risk in the opinion of the investigator

a. 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 (Appendix 3) and a QTc interval >0.47 second.

b. Uncontrolled heart failure or hypertension, uncontrolled diabetes mellitus, uncontrolled systemic infection

c. Patients with another active cancer (excluding 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.

11. Patient is currently enrolled in (or completed within 30 days before study drug administration) another investigational drug study

12. Patient is currently receiving treatment with any agent listed on the prohibited medication list such as valproic acid, other systemic cancer agents (with the exception of approved luteinising-hormone releasing hormone (LHRH) agonists such as goserelin or leuprolide. Oral Bisphosphonates initiated within 7 days prior to study drug. See Section 6.6 for complete list.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the efficacy of exemestane alone with exemestane plus entinostat, as determined by the duration of progression free survival (PFS) measured from the date of randomization;Secondary Objective: • Efficacy: To compare objective response rate (ORR) and clinical benefit response (CBR)<br><br>• Safety: To evaluate the safety and tolerability of entinostat in combination with exemestane as measured by adverse events and laboratory safety parameters <br>;Primary end point(s): Progression-free survival (PFS)