Study to Assess Food Effect on Pharmacokinetics of Entinostat in Subjects With Breast Cancer or Non-Small Cell Lung Cancer (ENCORE110)

A Phase I Study to Assess the Food Effect on the Pharmacokinetics of Entinostat in Postmenopausal Women With Locally Recurrent or Metastatic ER+ Breast Cancer and Men and Women With Progressive Non-Small Cell Lung Cancer

The purpose of this study is to evaluate the effect of food on the pharmacokinetics (PK) of the experimental drug, entinostat, in women with breast cancer and men and women with non-small cell lung cancer. The safety and tolerability of entinostat will also be evaluated when entinostat is given by itself as well as with the approved drugs, exemestane (Aromasin®) or erlotinib (Tarceva®). A biomarker (chemical "marker" in the blood/tissue that may be related to your response to the study drug) will also be tested.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Lung Cancer; Non Small Cell Lung Cancer (NSCLC); Estrogen Receptor Breast Cancer
• Intervention / Treatment: Drug: entinostat; Drug: Erlotinib; Drug: Exemestane

Detailed Description

This is Phase 1, randomized, open-label, study of entinostat. The study is designed to evaluate any food effect on the pharmacokinetics of entinostat.

Patients will be randomized to receive entinostat with or without food on Cycle 1 Day 1 (C1D1). Patients randomized to receive entinostat with food on C1D1 will receive a second dose of entinostat without food on Cycle 1 Day 15 (C1D15). Patients randomized to receive entinostat without food on C1D1 will receive a second dose of entinostat with food on C1D15. Each cycle in the study will be for 28 days duration. Blood samples will be obtained pre-dose and serial blood samples will be taken after each dose to assess pharmacokinetics. For Cycle 2 and all subsequent cycles, all patients will continue to receive entinostat on Days 1 and 15 of each cycle. Those with breast cancer will also receive exemestane orally once daily starting on Cycle 2 Day 1. Those with NSCLC will also receive erlotinib starting on Cycle 2 Day 1.

Patients will be assessed at screening and at pre-prescribed times during study enrollment using standard assessments. Patients will also be assessed for tumor response after each 2 cycles. Patients will continue receiving study treatment until tumor progression or adverse events occur which necessitate discontinuing therapy as determined by the Investigator.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Peggy and Charles Stephenson Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Breast Cancer Patients Only

• Postmenopausal female patients
• Histologically or cytologically confirmed ER+ breast cancer at initial diagnosis and now has current disease progression and is a candidate to receive exemestane

NSCLC Patients Only:

• Cytologically or histologically confirmed NSCLC of stage IIIb or IV
• Received 1 to 2 prior chemotherapy or chemoradiotherapy regimens for advanced NSCLC (excluding erlotinib and valproic acid) and now has disease progression and is a candidate to receive erlotinib

All Patients:

• Age ≥ 18 years
• Patient must have the following laboratory parameters at study screening: Hemoglobin ≥ 9.0 g/dL; unsupported platelets ≥ 100.0 10-9/L; ANC ≥ 2.0 x 10-9/L; Creatinine less than 2.5 times the upper limit of normal for the institution; AST and alanine transaminase (ALT) < 2.5 times the upper limit of normal for the institution
• Patients may have a history of brain metastasis as long as certain criteria are met

Exclusion Criteria:

• Pregnant or lactating women
• Patient has rapidly progressive or life-threatening metastases.
• Patient has had previous treatment with entinostat or any other HDAC inhibitor including valproic acid
• 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:

MI 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 seconds.

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

• Patients with 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: entinostat C1D1 fed; Entinostat: Beginning C1D1 fed; C1D15 fasted. Erlotinib: NSCLC pts beginning C2D1,150 mg, po, qd. Exemestane: Breast cancer pts beginning C2D1,25 mg, po, qd.	Drug: entinostat; 10 mg, po, q14 days, until progression or intolerable toxicity; Other Names: SNDX-275, MS-275; Drug: Erlotinib; Erlotinib: NSCLC pts beginning C2D1,150 mg, po, qd.; Other Names: Tarceva; Drug: Exemestane; Exemestane: Breast cancer pts beginning C2D1,25 mg, po, qd.; Other Names: Aromasin
Experimental: entinostat C1D1 fasted; Entinostat: Beginning C1D1 fasted; C1D15 fed. Erlotinib: NSCLC pts beginning C2D1,150 mg, po, qd. Exemestane: Breast cancer pts beginning C2D1,25 mg, po, qd.	Drug: entinostat; 10 mg, po, q14 days, until progression or intolerable toxicity; Other Names: SNDX-275, MS-275; Drug: Erlotinib; Erlotinib: NSCLC pts beginning C2D1,150 mg, po, qd.; Other Names: Tarceva; Drug: Exemestane; Exemestane: Breast cancer pts beginning C2D1,25 mg, po, qd.; Other Names: Aromasin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in pharmacokinetics of entinostat when subjects fed or fasted	The pharmacokinetics of entinostat will be analyzed from patient plasma samples: maximum plasma concentration, time of maximum plasma concentration, area under the plasma concentration-time curve from baseline to last measurable concentration and extrapolated to infinity, terminal elimination rate constant.	C1D1 (sequential), D2, 4, 6, 8, 11; C1D15 (sequential), 16, 18, 20, 22 25; C2D1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in laboratory values from baseline	Chemistry, hematology blood samples: changes from baseline will be evaluated.	Screening, C1D1, C1D15, C2D1, C3D1
Change in ECG results from baseline	Changes from baseline will be evaluated including analysis of QTc prolongation and QTc change from baseline.	Screening, C1D1 (sequential), D2, 4, 6, 8, 11; C1D15 (sequential), D16, 18, 20, 22, 25; C2D1; EOT
Difference in pharmacodynamics from baseline	Blood samples will be analyzed for changes from baseline in protein lysine acetylation as measured by peripheral blood monocytes. The food effect, changes after entinostat, and changes after exemestane and erlotinib will be evaluated.	C1D1, D2, D8; C1D15, D16, D22; C2D1; C3D1; EOT
Adverse events	Incidence of treatment emergent adverse events, serious adverse events, adverse events resulting in permanent discontinuation of study drug, and deaths occurring within 30-days of the last dose of study drug.	C1D1 , D2, 4, 6, 8, 11; C1D15, 16, 18, 20, 22 25; C2D1; D1 of each subsequent cycle through end of treatment

Collaborators and Investigators

• Sponsor: Syndax Pharmaceuticals
• Investigators: Study Director: William McCulloch, M.D., Syndax Pharmaceuticals; Principal Investigator: Howard A Burris, M.D., Tennessee Oncology, PLLC

Publications and helpful links

General Publications

• Witta SE, Jotte RM, Konduri K, Neubauer MA, Spira AI, Ruxer RL, Varella-Garcia M, Bunn PA Jr, Hirsch FR. Randomized phase II trial of erlotinib with and without entinostat in patients with advanced non-small-cell lung cancer who progressed on prior chemotherapy. J Clin Oncol. 2012 Jun 20;30(18):2248-55. doi: 10.1200/JCO.2011.38.9411. Epub 2012 Apr 16.

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: May 4, 2012
• First Submitted That Met QC Criteria: May 7, 2012
• First Posted (Estimate): May 9, 2012

Study Record Updates

• Last Update Posted (Actual): November 19, 2021
• Last Update Submitted That Met QC Criteria: November 11, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Respiratory Tract Diseases; Neoplasms; Erlotinib; lung neoplasms; lung diseases; Breast Neoplasms; Thoracic Neoplasms; Respiratory; Bronchial Neoplasms; Exemestane; Aromatase Inhibitors; Neoplasms by Site; Breast Diseases; Protein Kinase Inhibitors; Carcinoma, Bronchogenic; Respiratory Tract Neoplasms; carcinoma,non small cell lung
• Additional Relevant MeSH Terms: Skin Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Breast Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Breast Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Protein Kinase Inhibitors; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Histone Deacetylase Inhibitors; Erlotinib Hydrochloride; Exemestane; Entinostat
• Other Study ID Numbers: SNDX-275-0110