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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Syndax Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01594398
First received: May 4, 2012
Last updated: September 9, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Lung Cancer
Non Small Cell Lung Cancer (NSCLC)
Breast Cancer
Estrogen Receptor Breast Cancer
Drug: entinostat
Drug: Erlotinib
Drug: Exemestane
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Syndax Pharmaceuticals:

Primary Outcome Measures:
  • Difference in pharmacokinetics of entinostat when subjects fed or fasted [ Time Frame: C1D1 (sequential), D2, 4, 6, 8, 11; C1D15 (sequential), 16, 18, 20, 22 25; C2D1 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Screening, C1D1, C1D15, C2D1, C3D1 ] [ Designated as safety issue: Yes ]
    Chemistry, hematology blood samples: changes from baseline will be evaluated.

  • Change in ECG results from baseline [ Time Frame: Screening, C1D1 (sequential), D2, 4, 6, 8, 11; C1D15 (sequential), D16, 18, 20, 22, 25; C2D1; EOT ] [ Designated as safety issue: Yes ]
    Changes from baseline will be evaluated including analysis of QTc prolongation and QTc change from baseline.

  • Difference in pharmacodynamics from baseline [ Time Frame: C1D1, D2, D8; C1D15, D16, D22; C2D1; C3D1; EOT ] [ Designated as safety issue: No ]
    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 [ Time Frame: C1D1 , D2, 4, 6, 8, 11; C1D15, 16, 18, 20, 22 25; C2D1; D1 of each subsequent cycle through end of treatment ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 28
Study Start Date: May 2012
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: SNDX-275, MS-275
Drug: Erlotinib
Erlotinib: NSCLC pts beginning C2D1,150 mg, po, qd.
Other Name: Tarceva
Drug: Exemestane
Exemestane: Breast cancer pts beginning C2D1,25 mg, po, qd.
Other Name: 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 Name: SNDX-275, MS-275
Drug: Erlotinib
Erlotinib: NSCLC pts beginning C2D1,150 mg, po, qd.
Other Name: Tarceva
Drug: Exemestane
Exemestane: Breast cancer pts beginning C2D1,25 mg, po, qd.
Other Name: Aromasin

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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01594398

Locations
United States, Florida
Florida Cancer Specialists
Sarasota, Florida, United States, 34232
United States, Oklahoma
Peggy and Charles Stephenson Cancer Center
Oklahoma City, Oklahoma, United States, 73104
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Syndax Pharmaceuticals
Investigators
Study Director: William McCulloch, M.D. Syndax Pharmaceuticals
Principal Investigator: Howard A Burris, M.D. Tennessee Oncology, PLLC
  More Information

Publications:
Responsible Party: Syndax Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01594398     History of Changes
Other Study ID Numbers: SNDX-275-0110
Study First Received: May 4, 2012
Last Updated: September 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Syndax Pharmaceuticals:
carcinoma,non small cell lung
lung diseases
lung neoplasms
Respiratory
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Erlotinib
Protein Kinase Inhibitors
Breast Neoplasms
Neoplasms
Breast Diseases
Exemestane
Aromatase Inhibitors

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Exemestane
Aromatase Inhibitors
Erlotinib
Protein Kinase Inhibitors
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 29, 2014