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

NCT01594398 | Completed Phase 1

• 1 other identifier: SNDX-275-0110
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Lung Cancer; Non Small Cell Lung Cancer (NSCLC); Breast Cancer; Estrogen Receptor Breast Cancer

Keywords

carcinoma,non small cell lung; lung diseases; lung neoplasms; Respiratory; Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Respiratory Tract Diseases; Erlotinib; Protein Kinase Inhibitors; Breast Neoplasms; Neoplasms; Breast Diseases; Exemestane; Aromatase Inhibitors

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Change in laboratory values from baseline

  Screening, C1D1, C1D15, C2D1, C3D1

• Change in ECG results from baseline

  Screening, C1D1 (sequential), D2, 4, 6, 8, 11; C1D15 (sequential), D16, 18, 20, 22, 25; C2D1; EOT

• Difference in pharmacodynamics from baseline

  C1D1, D2, D8; C1D15, D16, D22; C2D1; C3D1; EOT

• Adverse events

  C1D1 , D2, 4, 6, 8, 11; C1D15, 16, 18, 20, 22 25; C2D1; D1 of each subsequent cycle through end of treatment

Study Arms (2)

entinostat C1D1 fed

EXPERIMENTAL

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; Drug: Erlotinib; Drug: Exemestane

entinostat C1D1 fasted

EXPERIMENTAL

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; Drug: Erlotinib; Drug: Exemestane

Interventions

entinostat DRUG

10 mg, po, q14 days, until progression or intolerable toxicity

Also known as: SNDX-275, MS-275

entinostat C1D1 fed

Erlotinib DRUG

Erlotinib: NSCLC pts beginning C2D1,150 mg, po, qd.

Also known as: Tarceva

entinostat C1D1 fed

Exemestane DRUG

Exemestane: Breast cancer pts beginning C2D1,25 mg, po, qd.

Also known as: Aromasin

entinostat C1D1 fed

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Syndax Pharmaceuticals: lead

Study Sites (3)

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Peggy and Charles Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Related Publications (1)

• 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.

  PMID: 22508830 BACKGROUND

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Breast Neoplasms; Lung Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Respiratory Tract Diseases; Neoplasms; Breast Diseases

Interventions

entinostat; Erlotinib Hydrochloride; exemestane

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases; Bronchial Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• William McCulloch, M.D.

  Syndax Pharmaceuticals

  STUDY DIRECTOR

• Howard A Burris, M.D.

  Tennessee Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2012
• First Posted: May 9, 2012
• Study Start: May 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: May 1, 2014
• Last Updated: November 19, 2021

Record last verified: 2021-11

Locations

US (3)