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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


Phase 1
18 Years
90 Years
Open (Enrolling)
Both
Lung Cancer, Non Small Cell Lung Cancer (NSCLC), Breast Cancer, ER+ Breast Cancer

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Trial Information

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


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.


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.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Difference in pharmacokinetics of entinostat when subjects fed or fasted

Outcome Description:

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.

Outcome Time Frame:

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

Safety Issue:

No

Principal Investigator

William McCulloch, M.D.

Investigator Role:

Study Director

Investigator Affiliation:

Syndax Pharmaceuticals

Authority:

United States: Food and Drug Administration

Study ID:

SNDX-275-0110

NCT ID:

NCT01594398

Start Date:

May 2012

Completion Date:

December 2013

Related Keywords:

  • Lung Cancer
  • Non Small Cell Lung Cancer (NSCLC)
  • Breast Cancer
  • ER+ Breast Cancer
  • 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
  • Breast Neoplasms
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms

Name

Location
Florida Cancer Specialists Fort Myers, Florida  33901
Sarah Cannon Research Institute Nashville, Tennessee  37203
Peggy and Charles Stephenson Cancer Center Oklahoma City, Oklahoma  73104