A Phase 2 Exploratory Study of Erlotinib and SNDX-275 in Participants With Non-small Cell Lung Carcinoma Who Are Progressing on Erlotinib

Study Overview
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Brief Summary
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To evaluate the tumor responses to SNDX-275 (entinostat) in combination with continued erlotinib in participants with non-small Cell Lung Carcinoma (NSCLC) who are progressing on erlotinib.

Official Title
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A Phase 2, Exploratory Study of Erlotinib and SNDX-275 in Patients With Non-small Cell Lung Carcinoma Who Are Progressing on Erlotinib

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Entinostat
* Drug: Erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cytologically or histologically confirmed NSCLC of stage IIIb (pleural effusion) or IV Disease is progressing (either no response to treatment or subsequent relapse after an objective response) on erlotinib treatment, based on at least 2 scans (the last being within 4 weeks of study enrollment and can serve as the baseline scan for the participant's screening into the study) Recovered from any toxicity associated with the most recent cancer treatment (no greater than grade 1 toxicity on Common Terminology Criteria for Adverse Events scale or to prior baseline condition) At least 1 measurable lesion ≥ 20 millimeters (mm) by conventional computed tomography (CT) scan or ≥ 10 mm by spiral CT scan Eastern Cooperative Oncology Group performance score of 0, 1, or 2 and life expectancy of at least 3 months Paraffin-embedded tumor specimen available for correlative studies Male or female over 18 years of age Hemoglobin ≥ 9.0 grams/deciliter; platelets ≥ 75 x 10^9/liter (L); absolute neutrophil count ≥ 1.0 x 10^9/L without the use of hematopoietic growth factors Coagulation tests within the normal range Bilirubin and creatinine less than 2 times the upper limit of normal for the institution Aspartate aminotransferase and alanine aminotransferase less than 3 times the upper limit of normal for the institution Potassium, magnesium and phosphorus within the normal range for the institution (supplementation is permissible) Willing to use accepted and effective methods of contraception during the study (both men and women as appropriate) and for 3 months after the last dose of entinostat Participant or legally acceptable representative has granted written informed consent before any study-specific procedure (including special screening tests) is performed Exclusion Criteria: Prior stem cell transplant Symptomatic central nervous system involvement Prior treatment with an histone deacetylase inhibitor Concurrent anticancer therapy, with the exception of radiotherapy for a non-target study lesion Currently taking medication(s) on the prohibited medication list Systemic chemotherapy or treatment with an investigational agent within 28 days before enrollment Current use of valproic acid Untreated or unstable brain metastases, or taken steroids for this condition within 4 weeks of study drug administration Currently active second malignancy, or any malignancy within the last 5 years other than cured basal or squamous cell skin carcinoma, cervical carcinoma in situ, or superficial bladder cancer Inability to swallow oral medications or a gastrointestinal malabsorption condition Uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals, known human immunodeficiency virus infection, or active hepatitis B or C infection Abnormal cardiac function as defined as clinically significant findings on electrocardiogram (multifocal premature ventricular complexes, ST-T wave changes consistent with myocardial infarction or acute ischemia, QTc greater than 500 milliseconds), tachycardia, or left ventricular ejection fraction less than 40% on multigated acquisition scan Another serious or uncontrolled medical condition within 3 months of enrollment such as hypertension, diabetes mellitus, or suppressed immune system Known hypersensitivity to benzamides Morbid obesity Women who are currently pregnant or breast-feeding Participant is currently enrolled in (or completed within 28 days) another investigational drug study Participant unavailable for on-study or follow-up assessments Participant has any kind of medical, psychiatric, or behavioral disorder that places the participant at increased risk for study participation or compromises the ability of the participant to give written informed consent and/or to comply with study procedures and requirements

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erlotinib-responsive<br>Participants self-administered entinostat in combination with continued erlotinib self-administration. Erlotinib-responsive participants are those who progressed following either a complete or partial response to erlotinib or a period of stable disease lasting at least 3 months. | Drug: Entinostat<br>* Entinostat (10 milligrams [mg] fixed dose orally [PO] every 2 weeks [Q2W]) on Days 1 and 15 of a 28-day cycle for up to 6 cycles<br>* Other names: SNDX-275;Drug: Erlotinib<br>* Erlotinib (150 mg PO QD) for up to six (6) 28-day cycles<br>* Other names: Tarceva;|
| Experimental: Erlotinib-nonresponsive<br>Participants self-administered entinostat in combination with continued erlotinib self-administration. Erlotinib-nonresponsive participants are those who either progressed immediately during treatment with erlotinib (after at least 1 full cycle of erlotinib treatment) or had an objective response or period of stable disease lasting less than 3 months. | Drug: Entinostat<br>* Entinostat (10 milligrams [mg] fixed dose orally [PO] every 2 weeks [Q2W]) on Days 1 and 15 of a 28-day cycle for up to 6 cycles<br>* Other names: SNDX-275;Drug: Erlotinib<br>* Erlotinib (150 mg PO QD) for up to six (6) 28-day cycles<br>* Other names: Tarceva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (Complete Response, Partial Response, or Stable Disease for at Least 3 Months |  | At least 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival Rate |  | Up to 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lung cancer, non small cell lung cancer