Clinical trial NCT01594398: Study to Assess Food Effect on Pharmacokinetics of Entinostat in Subjects With Breast Cancer or Non-Small Cell Lung Cancer
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
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Syndax Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2012-05-09
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Difference in pharmacokinetics of entinostat when subjects fed or fasted
timeFrame: C1D1 (sequential), D2, 4, 6, 8, 11; C1D15 (sequential), 16, 18, 20, 22 25; C2D1
Secondary outcomes:
measure: Change in laboratory values from baseline
timeFrame: Screening, C1D1, C1D15, C2D1, C3D1
measure: Change in ECG results from baseline
timeFrame: Screening, C1D1 (sequential), D2, 4, 6, 8, 11; C1D15 (sequential), D16, 18, 20, 22, 25; C2D1; EOT
measure: Difference in pharmacodynamics from baseline
timeFrame: C1D1, D2, D8; C1D15, D16, D22; C2D1; C3D1; EOT
measure: Adverse events
timeFrame: C1D1 , D2, 4, 6, 8, 11; C1D15, 16, 18, 20, 22 25; C2D1; D1 of each subsequent cycle through end of treatment
Other outcomes:
Locations:
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Oklahoma City
country: United States
facility: Peggy and Charles Stephenson Cancer Center
state: Oklahoma
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
Study officials:
affiliation: Syndax Pharmaceuticals
name: William McCulloch, M.D.
role: STUDY_DIRECTOR
affiliation: Tennessee Oncology
name: Howard A Burris, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.