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

NCT ID: NCT01594398

Last Updated: 2021-11-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

14 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-05-31

Study Completion Date

2014-05-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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

Keywords

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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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

entinostat

Intervention Type DRUG

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

Erlotinib

Intervention Type DRUG

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

Exemestane

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

entinostat

Intervention Type DRUG

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

Erlotinib

Intervention Type DRUG

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

Exemestane

Intervention Type DRUG

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

Interventions

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entinostat

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

Intervention Type DRUG

entinostat

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

Intervention Type DRUG

Erlotinib

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

Intervention Type DRUG

Erlotinib

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

Intervention Type DRUG

Exemestane

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

Intervention Type DRUG

Exemestane

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

Intervention Type DRUG

Other Intervention Names

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SNDX-275, MS-275 SNDX-275, MS-275 Tarceva Tarceva Aromasin Aromasin

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Syndax Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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William McCulloch, M.D.

Role: STUDY_DIRECTOR

Syndax Pharmaceuticals

Howard A Burris, M.D.

Role: PRINCIPAL_INVESTIGATOR

Tennessee Oncology

Locations

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Florida Cancer Specialists

Sarasota, Florida, United States

Site Status

Peggy and Charles Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 22508830 (View on PubMed)

Other Identifiers

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SNDX-275-0110

Identifier Type: -

Identifier Source: org_study_id