A Phase 2 Exploratory Study of Erlotinib and SNDX-275 in Participants With Non-small Cell Lung Carcinoma Who Are Progressing on Erlotinib
Condition: Non Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Entinostat; Erlotinib
Intervention description: 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; Erlotinib (150 mg PO QD) for up to six (6) 28-day cycles
Intervention MeSH terms: Erlotinib Hydrochloride; Entinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: lung cancer; non small cell lung cancer

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Cytologically or histologically confirmed NSCLC of stage IIIb (pleural effusion) or IV

          2. 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)

          3. 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)

          4. At least 1 measurable lesion ≥ 20 millimeters (mm) by conventional computed tomography
             (CT) scan or ≥ 10 mm by spiral CT scan

          5. Eastern Cooperative Oncology Group performance score of 0, 1, or 2 and life expectancy
             of at least 3 months

          6. Paraffin-embedded tumor specimen available for correlative studies

          7. Male or female over 18 years of age

          8. 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

          9. Coagulation tests within the normal range

         10. Bilirubin and creatinine less than 2 times the upper limit of normal for the
             institution

         11. Aspartate aminotransferase and alanine aminotransferase less than 3 times the upper
             limit of normal for the institution

         12. Potassium, magnesium and phosphorus within the normal range for the institution
             (supplementation is permissible)

         13. 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

         14. Participant or legally acceptable representative has granted written informed consent
             before any study-specific procedure (including special screening tests) is performed

        Exclusion Criteria:

          1. Prior stem cell transplant

          2. Symptomatic central nervous system involvement

          3. Prior treatment with an histone deacetylase inhibitor

          4. Concurrent anticancer therapy, with the exception of radiotherapy for a non-target
             study lesion

          5. Currently taking medication(s) on the prohibited medication list

          6. Systemic chemotherapy or treatment with an investigational agent within 28 days before
             enrollment

          7. Current use of valproic acid

          8. Untreated or unstable brain metastases, or taken steroids for this condition within 4
             weeks of study drug administration

          9. 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

         10. Inability to swallow oral medications or a gastrointestinal malabsorption condition

         11. Uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals,
             known human immunodeficiency virus infection, or active hepatitis B or C infection

         12. 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

         13. Another serious or uncontrolled medical condition within 3 months of enrollment such
             as hypertension, diabetes mellitus, or suppressed immune system

         14. Known hypersensitivity to benzamides

         15. Morbid obesity

         16. Women who are currently pregnant or breast-feeding

         17. Participant is currently enrolled in (or completed within 28 days) another
             investigational drug study

         18. Participant unavailable for on-study or follow-up assessments

         19. 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