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

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

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.

Study Overview

• Status: Terminated
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Entinostat; Drug: Erlotinib

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123
      • Sharp Clinical Oncology Research
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • New York
    • Buffalo, New York, United States
      • Roswell Park Cancer Institute
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University Of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Erlotinib-responsive; 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; 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; Other Names: SNDX-275; Drug: Erlotinib; Erlotinib (150 mg PO QD) for up to six (6) 28-day cycles; Other Names: Tarceva
Experimental: Erlotinib-nonresponsive; 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; 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; Other Names: SNDX-275; Drug: Erlotinib; Erlotinib (150 mg PO QD) for up to six (6) 28-day cycles; Other Names: Tarceva

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Syndax Pharmaceuticals
• Investigators: Study Chair: Alex Adjei, MD, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: September 8, 2008
• First Submitted That Met QC Criteria: September 8, 2008
• First Posted (Estimated): September 10, 2008

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: July 5, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: lung cancer; non small cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Histone Deacetylase Inhibitors; Erlotinib Hydrochloride; Entinostat
• Other Study ID Numbers: SNDX-275-0403