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

Primary Purpose

Lung Cancer, Non Small Cell Lung Cancer (NSCLC), Breast Cancer

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

entinostat

Erlotinib

Exemestane

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring 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

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Florida Cancer Specialists
Peggy and Charles Stephenson Cancer Center
Sarah Cannon Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

entinostat C1D1 fed

entinostat C1D1 fasted

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change in laboratory values from baseline

Chemistry, hematology blood samples: changes from baseline will be evaluated.

Change in ECG results from baseline

Changes from baseline will be evaluated including analysis of QTc prolongation and QTc change from baseline.

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.

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.

Full Information

NCT ID

NCT01594398

First Posted

May 4, 2012

Last Updated

November 11, 2021

Sponsor

Syndax Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01594398

Brief Title

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

Acronym

ENCORE110

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2021

Overall Recruitment Status

Completed

Study Start Date

May 2012 (undefined)

Primary Completion Date

April 2014 (Actual)

Study Completion Date

May 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Syndax Pharmaceuticals

4. Oversight

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

entinostat C1D1 fed

Arm Type

Experimental

Arm Description

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.

Arm Title

entinostat C1D1 fasted

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

entinostat

Other Intervention Name(s)

SNDX-275, MS-275

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

entinostat

Other Intervention Name(s)

SNDX-275, MS-275

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Erlotinib

Other Intervention Name(s)

Tarceva

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Erlotinib

Other Intervention Name(s)

Tarceva

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Exemestane

Other Intervention Name(s)

Aromasin

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Exemestane

Other Intervention Name(s)

Aromasin

Intervention Description

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

Primary Outcome Measure Information:

Title

Difference in pharmacokinetics of entinostat when subjects fed or fasted

Description

Time Frame

C1D1 (sequential), D2, 4, 6, 8, 11; C1D15 (sequential), 16, 18, 20, 22 25; C2D1

Secondary Outcome Measure Information:

Title

Change in laboratory values from baseline

Description

Chemistry, hematology blood samples: changes from baseline will be evaluated.

Time Frame

Screening, C1D1, C1D15, C2D1, C3D1

Title

Change in ECG results from baseline

Description

Changes from baseline will be evaluated including analysis of QTc prolongation and QTc change from baseline.

Time Frame

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

Title

Difference in pharmacodynamics from baseline

Description

Time Frame

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

Title

Adverse events

Description

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

William McCulloch, M.D.

Organizational Affiliation

Syndax Pharmaceuticals

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Howard A Burris, M.D.

Organizational Affiliation

Tennessee Oncology, PLLC

Official's Role

Principal Investigator

Facility Information:

Facility Name

Florida Cancer Specialists

City

Sarasota

State/Province

Florida

ZIP/Postal Code

34232

Country

United States

Facility Name

Peggy and Charles Stephenson Cancer Center

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73104

Country

United States

Facility Name

Sarah Cannon Research Institute

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

22508830

Citation

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.

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

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